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Mary Jane Meegan
Fellow Emeritus, Pharmacy

Biography

Mary J Meegan completed her PhD degree in UCD under the direction of Professor Dervilla Donnelly in the area of natural product chemistry and subsequently carried out postdoctoral research at the University Chemical Laboratory, Cambridge University in the research group of Professor Alan Battersby in the area of porphyrin synthesis and biosynthesis. Following further research periods at University College Dubin and CNRS Gif-sur-Yvette, she was appointed as lecturer in Pharmaceutical Chemistry at the School of Pharmacy and Pharmaceutical Sciences in Trinity College Dublin. She has research experience in the School of Pharmacy and and Pharmaceutical Sciences, Trinity College in the general area of pharmaceutical and medicinal chemistry, with over 100 peer-reviewed scientific papers covering topics such as design and synthesis of anticancer drugs, drug impurity profiling, synthetic methods for library design and in vitro screening. She has extensive experience in scientific and technical management having led an active research group, has acted as Head of the Department of Pharmaceutical Chemistry and as subject area head of Pharmaceutical Chemistry at the School of Pharmacy. Research collaborations have been established within Trinity College with Dr. Niamh O'Boyle (School of Pharmacy and Pharmaceutical Sciences), Dr D Zisterer, Dr D Fayne in the School of Biochemistry and Immunology and also with many European research centres. She is a member of several International Scientific Societies.

Publications and Further Research Outputs

Peer-Reviewed Publications

O'Boyle, NM, Barrett, I, Greene, LM, Carr, M, Fayne, D, Twamley, B, Knox, AJS, Keely, NO, Zisterer, DM, Meegan, MJ, Lead Optimization of Benzoxepin-Type Selective Estrogen Receptor (ER) Modulators and Downregulators with Subtype-Specific ERα and ERβ Activity, Journal of Medicinal Chemistry, 61, (2), 2018, p514 - 534 Journal Article, 2018 DOI URL TARA - Full Text

Andrew J. Byrne, Sandra A. Bright, Darren Fayne, James P. McKeown, Thomas McCabe, Brendan Twamley, Clive Williams and Mary J. Meegan, Synthesis, Antiproliferative and Pro-Apoptotic Effects of Nitrostyrenes and Related Compounds in Burkitt's Lymphoma, Medicinal Chemistry, 14 , (1), 2018, p181 - 199 Journal Article, 2018

Malebari, AM, Greene, LM, Nathwani, SM, Fayne, D, O'Boyle, NM, Wang, S, Twamley, B, Zisterer, DM, Meegan, MJ, β-Lactam analogues of combretastatin A-4 prevent metabolic inactivation by glucuronidation in chemoresistant HT-29 colon cancer cells, European Journal of Medicinal Chemistry, 130, 2017, p261-285 Journal Article, 2017 URL DOI

Niamh M. O'Boyle, Daniela M. Zisterer, Mary J. Meegan, Title: Microtubule-Destabilising Actions of Piperlongumine and Analogues, Proceedings of the 3rd Int. Electron. Conf. Med. Chem., 3rd International Electronic Conference on Medicinal Chemistry, November 2017, 3, 2017 Conference Paper, 2017 DOI URL

Meegan MJ, Nathwani S, Twamley B, Zisterer DM, O'Boyle NM., Piperlongumine (piplartine) and analogues: Antiproliferative microtubule-destabilising agents., European Journal of Medicinal Chemistry, 125, 2017, p453 - 463 Journal Article, 2017 TARA - Full Text DOI

Niamh M. O'Boyle, Daniela M. Zisterer, Mary J. Meegan, Lead Optimization of Benzoxepin-Type Selective Estrogen Receptor (ER) Modulators and Downregulators with Subtype-Specific ERα and ERβ Activity, Proceedings of the 3rd Int. Electron. Conf. Med. Chem., 3rd International Electronic Conference on Medicinal Chemistry, November 2017, 3, 2017 Conference Paper, 2017 URL DOI

Greene TF, Wang S, Greene LM, Nathwani SM, Pollock JK, Malebari AM, McCabe T, Twamley B, O'Boyle NM, Zisterer DM, Meegan MJ, Synthesis and Biochemical Evaluation of 3-Phenoxy-1,4-diarylazetidin-2-ones as Tubulin-Targeting Antitumor Agents., Journal of Medicinal Chemistry, 59, (1), 2016, p90 - 113 Journal Article, 2016 DOI URL TARA - Full Text

McNamara, Y. M. Bright, S. A. Byrne, A. J. Cloonan, Suzanne M. McCabe, T. Williams, D. C. Meegan, M. J., Synthesis and antiproliferative action of a novel series of maprotiline analogues, European Journal of Medicinal Chemistry, 2014 Journal Article, 2014 TARA - Full Text

Pollock, JK, Verma,NK, O'Boyle, NM, Carr, MG, Meegan, MJ, Zisterer, DM, Combretastatin (CA)-4 and its novel analogue CA-432 impair T-cell migration through the Rho/ROCK signalling pathway, Biochemical Pharmacology, 92, (4), 2014, p544-557 Journal Article, 2014 DOI

Pollock, J. K. Verma, N. K. O'Boyle, N. M. Carr, M. Meegan, M. J. Zisterer, D. M., Combretastatin (CA)-4 and its novel analogue CA-432 impair T-cell migration through the Rho/ROCK signalling pathway, Biochemical pharmacology, 92, (4), 2014, p544-557 Journal Article, 2014 DOI

O'Boyle, N. M. Pollock, J. K. Carr, M. Knox, A. J. Nathwani, S. M. Wang, S. Caboni, L. Zisterer, D. M. Meegan, M. J., beta-Lactam estrogen receptor antagonists and a dual-targeting estrogen receptor/tubulin ligand, Journal of Medicinal Chemistry , 57, (22), 2014, p9370-82 Journal Article, 2014 DOI

O'Boyle, NM, Pollock, JK, Carr, M, Knox, AJS, Nathwani, SM, Wang, S, Caboni, L, Zisterer, DM, Meegan, MJ, β-Lactam Estrogen Receptor Antagonists and a Dual-Targeting Estrogen Receptor/Tubulin Ligand, Journal of Medicinal Chemistry, 57, (22), 2014, p9370 - 9382 Journal Article, 2014 URL DOI TARA - Full Text

Caboni L, Egan B, Kelly B, Blanco F, Fayne D, Meegan MJ, Lloyd DG, Structure-activity relationships in non-ligand binding pocket (non-LBP) diarylhydrazide antiandrogens., Journal of chemical information and modeling, 53, (8), 2013, p2116-30 Journal Article, 2013 URL DOI

Nathwani, S. M., Hughes, L., Greene, L. M., Carr, M., O'Boyle, N. M., McDonnell, S., Meegan, M. J., Zisterer, D. M., Novel cis-restricted beta-lactam combretastatin A-4 analogues display anti-vascular and anti-metastatic properties in vitro,, Oncol Rep, 29, (2), 2013, p585 - 594 Journal Article, 2013

Greene, LM, Wang, S, O'Boyle, NM, Bright, SA, Reid, JEA, Kelly, PJ, Meegan, MJ, Zisterer, DM, Combretazet-3 a novel synthetic cis-stable combretastatin A-4-azetidinone hybrid with enhanced stability and therapeutic efficacy in colon cancer, Oncology Reports, 29, (6), 2013, p2451-2458 Journal Article, 2013 DOI

O'Boyle, N. M., Greene, L. M., Keely, N. O., Wang, S., Cotter, T. S., Zisterer, D. M., Meegan, M. J., Synthesis and biochemical activities of antiproliferative amino acid and phosphate derivatives of microtubule-disrupting beta-lactam combretastatins: , Eur J Med Chem., 62, 2013, p705 - 721 Journal Article, 2013

Greene, L. M., Wang, S., O'Boyle, N. M., Bright, S. A., Reid, J. E., Kelly, P., Meegan, M. J., Zisterer, D. M., Combretazet-3 a novel synthetic cis-stable combretastatin A-4-azetidinone hybrid with enhanced stability and therapeutic efficacy in colon cancer,, Oncol Rep, 29, (6), 2013, p2451 - 2458 Journal Article, 2013

Caboni, L. Egan, B., Kelly, B.,Blanco, F., Fayne, D., Meegan, M. J., Lloyd, D. G, Structure-Activity Relationships in Non-Ligand Binding Pocket (Non-LBP) Diarylhydrazide Antiandrogens,, J Chem Inf Model, 53, (8), 2013, p2116 - 2130 Journal Article, 2013

Orlagh M. Kelly, Yvonne M. McNamara, Lars H. Manzke, Mary J. Meegan, Richard K. Porter, The Preservation of in vivo Phosphorylated and Activated Uncoupling Protein 3 (UCP3) in Isolated Skeletal Muscle Mitochondria following Administration of 3,4-Methylenedioxymethamphetamine (MDMA aka Ecstasy) to Rats/Mice, Mitochondrion, 12, (1), 2012, p110-9 Journal Article, 2012 TARA - Full Text

Greene, L. M., O'Boyle, N. M., Nolan, D. P., Meegan, M. J., Zisterer, D. M., The vascular targeting agent Combretastatin-A4 directly induces autophagy in adenocarcinoma-derived colon cancer cells, Biochem Pharmacol, 84, (5), 2012, p612 - 624 Journal Article, 2012

Blanco, F., Egan, B., Caboni, L., Elguero, J. O'Brien, J., McCabe, T., Fayne, D., Meegan, M. J., Lloyd, D. G, Study of E/Z isomerization in a series of novel non-ligand binding pocket androgen receptor antagonists, J Chem Inf Model, 52, (9), 2012, p2387 - 2397 Journal Article, 2012

Keely, Niall O.; Zisterer, Daniela M.; Meegan, Mary J., Design, synthesis and biochemical evaluation of estrogen receptor ligand conjugates as tumour targeting agents , Letters in Drug Design & Discovery, 9, (3), 2012, p295 - 304 Journal Article, 2012

Greene, LM, O'Boyle, NM, Nolan, DP, Meegan, MJ, Zisterer, DM, The vascular targeting agent Combretastatin-A4 directly induces autophagy in adenocarcinoma-derived colon cancer cells, Biochemical Pharmacology, 84, (5), 2012, p612-624 Journal Article, 2012 DOI

Caboni, L., Kinsella, G. K., Blanco, F., Fayne, D., Jagoe, W. N., Carr, M., Williams, D. C., Meegan, M. J., Lloyd, D. G., "True" Antiandrogens-Selective Non-Ligand-Binding Pocket Disruptors of Androgen Receptor-Coactivator Interactions: Novel Tools for Prostate Cancer, , J Med Chem,, 55, (4 ), 2012, p1635 - 1644 Journal Article, 2012

Lisa M. Greene, Miriam Carr, Niall O. Keeley, Mark Lawler, Mary J. Meegan and Daniela M. Zisterer;, BubR1 is required for the mitotic block induced bycombretastatin-A4 and a novel cis-restricted ß-lactam analogue in human cancer cells;, International Journal of Molecular Medicine, 27, (5), 2011, p715 - 723 Journal Article, 2011

O'Boyle, NM, Greene, LM, Bergin, O, Fichet, JB, McCabe, T, Lloyd, DG, Zisterer, DM, Meegan, MJ, Synthesis, evaluation and structural studies of antiproliferative tubulin-targeting azetidin-2-ones, Bioorganic & Medicinal Chemistry, 19, (7), 2011, p2306-2325 Journal Article, 2011 TARA - Full Text

Yvonne M. McNamara, Suzanne M. Cloonan, Andrew J.S. Knox, John J. Keating, Stephen G. Butler, Günther H. Peters, Mary J. Meegan and D. Clive Williams, Synthesis and serotonin transporter activity of 1,3-bis(aryl)-2-nitro-1-propenes as a new class of anticancer agents, Bioorganic & Medicinal Chemistry, 19, (3), 2011, p1328 - 1348 Journal Article, 2011 TARA - Full Text

Lisa M. Greene, Miriam Carr, Niall O. Keeley, Mark Lawler, Mary J. Meegan and Daniela M. Zisterer;, BubR1 is required for the mitotic block induced bycombretastatin-A4 and a novel cis-restricted ß-lactam analogue in human cancer cells;, International Journal of Molecular Medicine, 27, (5), 2011, p715 - 723 Journal Article, 2011

O'Boyle, NM, Meegan, MJ, Designed multiple ligands for cancer therapy, Current Medicinal Chemistry, 18, (31), 2011, p4722-4737 Journal Article, 2011 DOI

O'Boyle, NM, Carr, M, Greene, LM, Keely, NO, Knox, AJS, McCabe, T, Lloyd, DG, Zisterer, DM, Meegan, MJ, Synthesis, Biochemical and Molecular Modelling Studies of Antiproliferative Azetidinones causing Microtubule Disruption and Mitotic Catastrophe, European Journal of Medicinal Chemistry, 46, (9), 2011, p4595 - 4607 Journal Article, 2011 TARA - Full Text

O'Boyle, N.M., Knox, A.J.S., Price, T.P., Williams, D.C., Zisterer, D.M., Lloyd, D.G., Meegan, M.J.,, Lead identification of beta-lactam and related imine inhibitors of the molecular chaperone heat shock protein 90, Bioorganic & Medicinal Chemistry, 19, (20), 2011, p6055-6068 Journal Article, 2011 DOI TARA - Full Text

Nathwani, S-M., Butler, S., Meegan, M.J., Campiani, G., Lawler, M., Williams, D.C. & Zisterer, D.M., Dual targeting of tumour cells and host endothelial cells by novel microtubule-targeting agents, pyrrolo-1,5-benzoxazepines., Cancer Chemotherapy and Pharmacology, 65, (2), 2010, p289-300 Journal Article, 2010 TARA - Full Text

Miriam Carr, Lisa M. Greene, Andrew J.S. Knox, David G Lloyd, Daniela M. Zisterer and Mary J. Meegan, Lead identification of conformationally restricted β-lactam type combretastatin analogues: synthesis, antiproliferative activity and tubulin targeting effects, European Journal of Medicinal Chemistry, 45, (12), 2010, p5752-5766 Journal Article, 2010 TARA - Full Text

Greene LM, Nathwani SM, Bright SA, Fayne D, Croke A, Gargliardi M, Mc Elligott AM, O'Connor L, Carr M, Keely NO, O'Boyle NM, Carroll P, Sarkadi B, Conneally E, Lloyd DG, Lawler M, Meegan MJ, Zisterer DM, The vascular targeting agent Combretastatin-A4 and a novel cis-restricted {beta}-lactam analogue CA-432 induce apoptosis in human chronic myeloid leukemia cells and in ex vivo patient samples including those displaying multidrug resistance., The Journal of Pharmacology and Experimental Therapeutics, 335, (2), 2010, p302 - 313 Journal Article, 2010 DOI

Suzanne M. Cloonan, John J. Keating, John E. O'Brien, Desmond Corrigan, Pierce V Kavanagh, D. Clive Williams and Mary J. Meegan, Synthesis and in vitro toxicity of 4-MTA, its characteristic clandestine synthesis byproducts and related sulphur substituted á-alkylthioamphetamines, Bioorganic and Medicinal Chemistry, 18, 2010, p4009 - 4031 Journal Article, 2010 TARA - Full Text

Barrett I, Carr M, O'Boyle N, Greene LM, Knox AJ, Lloyd DG, Zisterer DM, Meegan MJ, Lead identification of conformationally restricted benzoxepin type combretastatin analogs: synthesis, antiproliferative activity, and tubulin effects., Journal of enzyme inhibition and medicinal chemistry, 25, (2), 2010, p180-94 Journal Article, 2010 DOI

Yang Y, Carta G, Peters MB, Price T, O'Boyle N, Knox AJ, Fayne D, Williams DC, Meegan MJ, Lloyd DG , 'tieredScreen' - Layered Virtual Screening Tool for the Identification of Novel Estrogen Receptor Alpha, Molecular Informatics, 29, 2010, p421 - 430 Journal Article, 2010 DOI

O'Boyle NM, Carr M, Greene LM, Bergin O, Nathwani SM, McCabe T, Lloyd DG, Zisterer DM, Meegan MJ, Synthesis and evaluation of azetidinone analogues of combretastatin A-4 as tubulin targeting agents, Journal of Medicinal Chemistry, 53, (24), 2010, p8569-8584 Journal Article, 2010 DOI TARA - Full Text

Bright S.A., Greene, L.M., Greene, T.F., Campiani, G., Buitini, S., Brindisi, M., Lawler, M., Meegan, M.J., Williams, D.C. and Zisterer, D.M. , The novel pyrrolo-1,5-benzoxazepine, PBOX-21, potentiates the apoptotic efficacy of STI571 (imatinib mesylate) in human chronic myeloid leukaemia cells, Biochemical Pharmacology, 77, (3), 2009, p310-321 Journal Article, 2009 URL DOI

Daniela Zisterer, Mary Meegan, Niamh O'Boyle, Miriam Carr, Lisa Greene and Thomas Greene, 'Combretastatin Derivatives and Uses Therefor', European Patent Office, EP2338877 A1, 2009 Patent, 2009 URL

Suzanne M. Cloonan, John J. Keating, Stephen G. Butler, Andrew J.S. Knox, Anne M. Jørgensen, Günther H. Peters, Dilip Rai,Desmond Corrigan, David G. Lloyd, D. Clive Williams and Mary J. Meegan, Synthesis and serotonin transporter activity of sulphur-substituted á-alkyl phenethylamines as a new class of anticancer agents, European Journal of Medicinal Chemistry, 44, (12), 2009, p4862 - 4888 Journal Article, 2009 DOI TARA - Full Text

Barrett, I., Meegan, M.J., Hughes, R.B., Carr, M., Knox, A.J.S. Artemenko, N., Golfis, G., Zisterer, D.M. & Lloyd, D.G., Synthesis, biological evaluation, structural-activity relationship, and docking study for a series of benzoxepin-derived estrogen receptor modulators., Bioorganic & Medicinal Chemistry, 16, (21), 2008, p9554-9973 Journal Article, 2008 DOI URL

Butler, S. G., Meegan, M. J., , Recent developments in the design of anti-depressive therapies: targeting the serotonin transporter, Curr Med Chem, 15 , (17), 2008, p1737-6- Journal Article, 2008

Meegan, M.J., Carr, M., Knox, A.J.S., Zisterer, D.M. & Lloyd, D.G., Beta-Lactam type molecular scaffolds for antiproliferative activity: Synthesis and cytotoxic effects in breast cancer cells., Journal of Enzyme Inhibition and Medicinal Chemistry, 23, (5), 2008, p668-685 Journal Article, 2008 URL DOI URL

Knox, AJS; Yang, YD; Lloyd, DG; Meegan, MJ, Virtual screening of the estrogen receptor , EXPERT OPINION ON DRUG DISCOVERY , 3, (8), 2008, p853-866 Journal Article, 2008

Knox AJS, Yang YD, Lloyd DG, Meegan, MJ, Virtual screening of the estrogen receptor, Expert opinion on drug discovery, 3, (8), 2008, p853 - 866 Journal Article, 2008 DOI

Barrett, I., Meegan, M. J.,Hughes, R. B., Carr, M., Knox, A. J., Artemenko, N., Golfis, G., Zisterer, D. M., Lloyd, D. G.,, Synthesis, biological evaluation, structural-activity relationship, and docking study for a series of benzoxepin-derived estrogen receptor modulators, Bioorg Med Chem; , 16, (21), 2008, p9554-73- Journal Article, 2008

Meegan, M. J., Carr, M., Knox, A. J., Zisterer, D. M., Lloyd, D. G., , Beta-lactam type molecular scaffolds for antiproliferative activity: synthesis and cytotoxic effects in breast cancer cells, J Enzyme Inhib Med Chem, 23, , (5), 2008, p668-85- Journal Article, 2008

Bright, S. A.,Greene, L. M.,Greene, T. F.,Campiani, G.,Butini, S.,Brindisi, M., Lawler, M., Meegan, M. J., Williams, D. C., Zisterer, D. M.;, The novel pyrrolo-1,5-benzoxazepine, PBOX-21, potentiates the apoptotic efficacy of STI571 (imatinib mesylate) in human chronic myeloid leukaemia cells, Biochem Pharmacol, 2008, October 30, 2008 Journal Article, 2008

Mary J Meegan, Irene Barrett, Jochen Zimmermann, Andrew J.S.Knox, Daniela M Zisterer, and David G Lloyd; , 6. Benzothiepin derived molecular scaffolds for estrogen eceptor modulators: synthesis and antagonistic effects in breast cancer cells, Journal of Enzyme Inhibition and Medicinal Chemistry, 22 , (5), 2007, p655-666.- Journal Article, 2007

Knox AJ, Meegan MJ, Sobolev V, Frost D, Zisterer DM, Williams DC, Lloyd DG., Target specific virtual screening: optimization of an estrogen receptor screening platform., Journal of Medicinal Chemistry, 50, (22), 2007, p5301-5310 Journal Article, 2007 DOI URL

Andrew J. S. Knox, Mary J. Meegan, Vladimir Sobolev, Dermot Frost, Daniela M. Zisterer, D. Clive Williams, and David G. Lloyd, , 5. Target Specific Virtual Screening: Optimization of an Estrogen Receptor Screening Platform, Journal of Medicinal Chemistry, , 50, (22), 2007, p5301-10- Journal Article, 2007

Smith, H.M., Knox, A.S., Zisterer, D.M., Lloyd, D.G., & Meegan, M.J. , Flexible estrogen receptor modulators: synthesis, biochemistry and molecular modeling studies for 3-benzyl-4,6-diarylhex-3-ene and 3,4,6-triarylhex-3-ene derivatives., Medicinal Chemistry, 3, (2), 2007, p135 - 155 Journal Article, 2007

David G. Lloyd, Helena M. Smith, Andrew S. Knox, Daniela M. Zisterer and Mary J. Meegan, , 1. Flexible Estrogen Receptor Modulators: Synthesis, Biochemistry and Molecular Modeling Studies for 3-Benzyl-4,6-diarylhex-3-ene and 3,4,6-Triarylhex-3-ene Derivatives; , Medicinal Chemistry, 3, 2007, p135 - 155 Journal Article, 2007

Meegan, M.J., Barrett, I., Zimmmermann, J., Knox, A.J.S., Zisterer, D.M. & Lloyd, D.G. , Benzothiepin-derived molecular scaffolds for estrogen receptor modulators: synthesis and antagonistic effects in breast cancer cells. , Journal of Enzyme Inhibition and Medicinal Chemistry, 22, (5), 2007, p655-66 Journal Article, 2007

David G. Lloyd, Georgia Golfis, Andrew J.S. Knox, Darren Fayne, Mary J. Meegan and Tudor I. Oprea, Oncology Exploration : Charting Cancer Medicinal Chemistry Space , Drug Discovery Today, 11, (3/4), 2006, p149 - 159 Journal Article, 2006

Andrew J S Knox, Mary J Meegan and David G Lloyd, Estrogen Receptors; Molecular Interactions, Virtual screening and Future Prospects, Current Topics in Medicinal Chemistry, 6, (2), 2006, p211 - 237 Journal Article, 2006

Lloyd, D.G., Smith, H.M., O'Sullivan, T., Knox, A.S., Zisterer, D.M. & Meegan, M.J. , Antiestrogenically active 2-benzyl-1,1-diarylbut-2-enes : Synthesis, Structure-Activity Relationships and Molecular Modeling Study for Flexible Estrogen Receptor Antagonists , Medicinal Chemistry, 2, (2), 2006, p147 - 168 Journal Article, 2006 URL

Meegan, M.J., , Nuclear Receptors as targets in Drug Discovery: Medicinal and Therapeutic Potential; , Current Topics in Medicinal Chemistry, , 6, , , (3), 2006, p179- Journal Article, 2006

Knox AJS, Meegan MJ, Lloyd DG, Estrogen Receptor: Molecular Interactions, Virtual Screening and Future Prospects., Current Topics in Medicinal Chemistry, 6, (3), 2006, p217 - 243 Journal Article, 2006 URL

David G. Lloyd, Helena M. Smith, Timothy O'Sullivan, Andrew S. Knox,, Antiestrogenically active 2-benzyl-1,1-diarylbut-2-enes : Synthesis, Structure-Activity Relationships and Molecular Modeling Study for Flexible Estrogen Receptor Antagonists;, Medicinal Chemistry, 2, (2), 2006, p147 - 168 Journal Article, 2006

Lloyd DG, Smith HM, O'Sullivan T, Zisterer DM, Meegan MJ, Synthesis, Structure-Activity Relationships and Antagonistic Effects in Human MCF-7 Breast Cancer Cells of Flexible Estrogen Receptor Modulators, Medicinal Chemistry, 1, (4), 2005, p335 - 353 Journal Article, 2005 DOI URL

Knox AS, Meegan MJ, Carta G, Lloyd DG, Considerations in Compound Database Preparations Hidden Impact on Virtual Screening Results, Journal of Chemical Information and Modelling, 45, (6), 2005, p1908 - 1919 Journal Article, 2005 URL DOI

Understanding the molecular mechanism of estrogen receptor modulators in, editor(s)Atta-ur-Rhaman, Reitz A B , Frontiers in Medicinal Chemistry, Bentham Science Publishers, 2005, pp183 - 231, [David G. Lloyd, Mary J. Meegan] Book Chapter, 2005

David G. Lloyd, Helena M. Smith, Timothy O'Sullivan, Daniela M. Zisterer , Synthesis, Structure-Activity Relationships and Antagonistic Effects in Human MCF-7 Breast Cancer Cells of Flexible Estrogen Receptor Modulators, Medicinal Chemistry, 1, (4), 2005, p335 - 353 Journal Article, 2005

Lloyd DG, Hughes RB, Zisterer DM, Williams DC, Fattorusso C, Catalanotti B, Campiani G, Meegan MJ., Benzoxepin-derived estrogen receptor modulators: a novel molecular scaffold for the estrogen receptor, Journal of Medicinal Chemistry, 47, (23), 2004, p5612 - 5615 Journal Article, 2004 DOI URL

David G. Lloyd, Rosario B. Hughes, Daniela M. Zisterer, D. Clive Williams, Caterina Fattorusso, Bruno Catalanotti, Giuseppe Campiani, Mary J. Meegan, Benzoxepin derived estrogen receptor modulators: A novel molecular scaffold for the estrogen receptor, Journal of Medicinal Chemistry, 47, 2004, p5612 Journal Article, 2004

MJ Meegan and DG Lloyd, Advances in the Science of Estrogen Receptor Modulation, Current Medicinal Chemistry, 10, 2003, p181 - 210 Journal Article, 2003

A.D. Neary, C.M. Burke, A.C. O'Leary and Mary J. Meegan. , Transformation of 4-acetoxy-3-vinylazetidin-2-ones to 3-(1-hydroxyethyl)azetidin-2-ones and 3-ethylideneazetidin2-onens: intermediates for carbapenem antibiotics. , Journal of Chemical Research, (S) , 2001, p166 - 169 Journal Article, 2001

Meegan MJ, Hughes RB, Lloyd DG, Williams DC, Zisterer DM, Ethyl side-chain modifications in novel flexible antiestrogens--design, synthesis and biological efficacy in assay against the MCF-7 breast tumor cell line, Anticancer Drug Design , 16, (1), 2001, p57 - 69 Journal Article, 2001 URL

M.J. Meegan, R.B. Hughes, D.G. Lloyd, D.C. Williams and D.M. Zisterer., Anti-Cancer Drug Design,, Ethyl side chain modifications in novel flexible antiestrogens - design, synthesis and biological efficacy in essay against the MCF-7 breast tumor cell line, 16, 2001, p57 - 69 Journal Article, 2001

A.D. Neary, C.M. Burke, A.C. O'Leary and Mary J. Meegan, Transformation of 4-acetoxy-3-vinylazetidin-2-ones to 3-(1-hydroxyethyl)azetidin-2-ones and 3-ethylideneazetidin2-onens: intermediates for carbapenem antibiotics. , Journal of Chemical Research,(M), 2001, p501 - 522 Journal Article, 2001

Meegan, M., Hughes, R., Lloyd, D.G., Zisterer, D.M. & Williams, D.C. , Flexible estrogen receptor modulators: design, synthesis and antagonistic effects in human MCF-7 breast cancer cells. , Journal Medicinal Chemistry, 44, (7), 2001, p1072 - 1084 Journal Article, 2001 DOI URL

M.J. Meegan, R.B. Hughes, D.G. Lloyd, D.C. Williams and D.M. Zisterer,, 'Flexible estrogen receptor modulators - design, synthesis and antagonistic effects in human MCF-7 breast cancer cells', Journal of Medicinal Chemistry, 44, (7), 2001, p1072 - 1084 Journal Article, 2001

P. Kavanagh, J. Dunne, J. Feely, R. Maguire, D. Corrigan, J.J. Keating, M.J. Meegan, J.M. Clancy and J. Burdett, 47. Prenylalkylamine abuse among opiate addicts attending a methadone treatment programme in the Republic of Ireland, Addiction Biology, 7, 2001, p177 - 181 Journal Article, 2001

D.G. Lloyd and M.J. Meegan, 45. 'Recent advances in estrogen receptor antagonists' , I Drugs , 3, (6), 2000, p632 - 642 Journal Article, 2000

Lloyd DG, Meegan MJ , Recent advances in estrogen receptor antagonists , IDrugs , 3, (6), 2000, p632 - 642 Journal Article, 2000 URL

P.V. Kavanagh, D. Corrigan, R.T. Maguire, M.J. Meegan, J.J. Keating, J. Clancy and J. Burdett, . Excretion profile of 4-Methylthioamphetamine in Dogs, Pharmacy and Pharmacology Communications., , 5, 1999, p653 - 655 Journal Article, 1999

A.C. O'Leary, C.M. Waldron, C.M. Burke, R.D. Keaveny and M.J. Meegan., 3-(2-Alkoxy-1-hydroxyethyl)azetidin-2-ones: potential intermediates for the synthesis of novel carbapenems, Journal of Chemical Research(M) , 1998, p434 - 456 Journal Article, 1998

A.C. O'Leary, C.M. Waldron, C.M. Burke, R.D. Keaveny and M.J. Meegan., 3-(2-Alkoxy-1-hydroxyethyl)azetidin-2-ones: potential intermediates for the synthesis of novel carbapenems, , Journal of Chemical Research(S) , 1998, p64 - 65 Journal Article, 1998

M.J. Meegan, C.M. Waldron, R.D. Keaveny and A.D. Neary, 4-Acetoxy-3-[1-(2-arylamino-1-hydroxy)ethyl]azetidin-2-ones: intermediates for the synthesis of novel carbapenems(S), Journal of Chemical Research , 1997, p158 - 159 Journal Article, 1997

. M.J. Meegan, C.M. Waldron, R.D. Keaveny and A.D. Neary., 4-Acetoxy-3-[1-(2-arylamino-1-hydroxy)ethyl]azetidin-2-ones: intermediates for the synthesis of novel carbapenems, , Journal of Chemical Research (M), 1997, p1101 - 1126 Journal Article, 1997

T.A. Nakib, P. Perjesi, R. Varghese and M.J. Meegan., Benzlideneindanones and benzylidenebenzosuberones: relationship of structure, antimcotic activity and acute toxicity, Medical Principles Practice, 6, 1997, p12 - 21 Journal Article, 1997

O.M. Walsh, M.J. Meegan, R.C. Prendergast and T.Al Nakib, Synthesis of 3-acetoxyazetidin-2-ones and 3-hydroxyazetidin-2-ones with antifungal and antibacterial activity, European Journal of Medicinal Chemistry, 31, 1996, p989 - 1000 Journal Article, 1996

Fiona M. Murphy and Mary J. Meegan, A New Synthesis of the 1,4-Dihydroindeno[1,2-b]pyrrole Heterocycle", Journal of Chemical Research(S), , 1996, p10 - 11 Journal Article, 1996

Fiona M. Murphy and Mary J. Meegan, A New Synthesis of the 1,4-Dihydroindeno[1,2-b]pyrrole Heterocycle, Journal of Chemical Research (M), , 1996, p301 - 315 Journal Article, 1996

. A.C. O'Leary, A.D. Neary, C.M. Waldron and M.J. Meegan, Transformation of 3-Isopropenylazetidin-2-ones to 3-[1-(Hydroxymethyl)ethylidene}azetidin-2-ones,, Journal of Chemical Research (M), , 1996, p2162 - 2191 Journal Article, 1996

A.C. O'Leary, A.D. Neary, C.M. Waldron and M.J. Meegan., Transformation of 3-Isopropenylazetidin-2-ones to 3-[1-(Hydroxymethyl)ethylidene}azetidin-2-ones, Journal of Chemical Research(S), , 1996, p368 - 369 Journal Article, 1996

E. P. Cooke, O. M. Walsh and M. J. Meegan., Reaction of Mixed Anhydrides with Imines:, Journal of Chemical Research(M), 1994, p2724 - 2759 Journal Article, 1994

E. P. Cooke, O. M. Walsh and M. J. Meegan., Reaction of Mixed Anhydrides with Imines:, J. Chem. Research(S), 1994, p470 - 471 Journal Article, 1994

M. J. Meegan, S. J. Harris and A. M. Kinahan., Synthesis of 2-Azetidinones using Calixarenes as Phase Transfer Catalysts, Journal of Chemical Resarch(M), 1994, p1832 - 1845 Journal Article, 1994

M. J. Meegan, T. Al Nakib and M. L. Burke., Synthesis of 1-[2-(Benzo[b]thiophen-3-yl)-2-benzyloxyethyl]-1H-imidazoles and 1-[2-(benzo[b]thiophen-3-yl)-2-benzyloxyethyl-1H-1,2-4-triazoles with Antifungal Activity., Journal of Chemical Research(S), 1994, p170 - 171 Journal Article, 1994

M. J. Meegan, T. Al Nakib and M. L. Burke., Synthesis of 1-[2-(Benzo[b]thiophen-3-yl)-2-benzyloxyethyl]-1H-imidazoles and 1-[2-(benzo[b]thiophen-3-yl)-2-benzyloxyethyl-1H-1,2-4-triazoles with Antifungal Activity., Journal of Chemical Research(M), 1994, p1042 - 1059 Journal Article, 1994

M. J. Meegan, S. J. Harris and A. M. Kinahan., Synthesis of 2-Azetidinones using Calixarenes as Phase Transfer Catalysts., Journal of Chemical Resarch(S) , 1994, p324 - 325 Journal Article, 1994

C. Waldron and M. J. Meegan., 3-Vinyl-betalactams as intermediates for carbapenem antibiotics, Pharmaceutisch Weekblad Scientific Ed, 14, (5), 1992, p25 - 25 Journal Article, 1992

M. J. Meegan, Ailish Looney, Louise Burke and T. Al Nakib., Synthesis and antifungal activity of some 2-aryl-3-hydroxymethylbenzo[b]thiophenes., European Journal of Medicinal Chemistry,, 27, (9), 1992, p971 - 976 Journal Article, 1992

T. Al Nakib, M. Abu-Lisan, G. Al-Jahari and M. J. Meegan., Antimycotic Activity and Acute Toxicity of Benzopyranopyrans and Related Compounds., Medical Principles and Practice, 2, 1991, p222 - 227 Journal Article, 1991

M. J. Meegan, Bridget Fleming and Orla Walsh., Synthesis of Monocyclic beta-lactams by Solid Liquid Phase Transfer Reactions., Journal of Chemical Research (S) , 1991, p156 - 157 Journal Article, 1991

M. J. Meegan, T. Al Nakib, Brendan Fullam, V. Bezjak and S. Rashid., Synthesis and antifungal activity of 2-amino-4-aryl-4H - 5H-[1] benzothiopyrano[4,3-b]pyran-3-carbonitriles and 2-alkoxy-4-aryl-5H[1]benzothiopyrano[4,3-b]pyridine-3-carbonitriles., European Journal of Medicinal Chemistry, 26, 1991, p221 - 230 Journal Article, 1991

T. Al Nakib, V. Bezjak, M. J. Meegan and R. Chandy., Synthesis and antifungal activity of some 3-benzylidenechroman-4-ones, 3-benzylidenethiochroman-4-ones and 3-benzylidene-1-tetralones., European Jounal of Medicinal Chemistry , 25, 1990, p455 - 462 Journal Article, 1990

T. Al Nakib, N. J. Miller, S. Rashid and M. J. Meegan., An evaluation of the acute In vivo toxicity of benzylidenechroman-4-ones, 1-thiobenzylidenechroman-4-ones and benzylidenetetralones. , Drug and Chemical Toxicology, 13, 1990, p195 - 207 Journal Article, 1990

T. Al Nakib, V. Bezjak, S. Rashid, M. J. Meegan., Structure to Antimycotic Activity of Benzylidenechomanones against 6 Miconazole - Resistant Pathogenic Yeasts in vitro., Medical Principles and Practice, 2, 1990, p100 - 105 Journal Article, 1990

P. B. Deasy, M. P. Finan and M. J. Meegan., Preparation and characterization of lactic/glycolic acid polymers and copolymers., Journal of Microencapsulation, 6, (3), 1989, p369 - 378 Journal Article, 1989

D. V. Tyndall, J. P. Acton and M. J. Meegan., Arylation of 2,2-dimethyl-2H-1-benzopyrans with arylpalladium complexes: a new synthesis of the 4-aryl-2,2-dimethyl-2H-1-benzopyran (neoflavene) ring system., Proceedings of the Royal Irish Academy, 98B, 1989, p241 - 250 Journal Article, 1989

D. V. Tyndall, T. Al Nakib and M. J. Meegan., A novel synthetic route to phenyl-substituted pyridines., Tetrahedron Letters , 28, 1988, p2703 - 2706 Journal Article, 1988

M. J. Meegan, D. V. Tyndall and E. T. MCarthy., A new synthesis of 4-phenylpyrido[3,2-b][1,4]benzothiazines(1-azaphenothiazines)., Journal of Chemical Research,(S), 1988, p145 - 145 Journal Article, 1988

M. J. Meegan, D. V. Tyndall and E. T. MCarthy., A new synthesis of 4-phenylpyrido[3,2-b][1,4]benzothiazines(1-azaphenothiazines)., Journal of Chemical Research(M) , 1988, p1332 - 1352 Journal Article, 1988

M. J. Meegan., "The synthesis and antifungal activity of 6-hydroxy-11-thiopterocarpans, Journal of Pharmacy and Pharmacology, 38, 1986, p105 - 105 Journal Article, 1986

Furans and benzo derivatives, preparation and application in, Comprehensive heterocyclic chemistry, Oxford, Pergamon Press, 1984, pp657 - 712, [M. J. Meegan and D. M. X. Donnelly.] Book Chapter, 1984

D. M. X. Donnely, M. O'Sullivan, T. O'Criodan and M. J. Meegan., Dalbergia species Part XIII., Phytochemistry, 20, 1981, p1089 - 1092 Journal Article, 1981

A. R. Battersby, C. J. Fookes, E. McDonald, M. J. Meegan and H. Wurtziger., Biosynthesis of porphyrins and related macrocycles, Part 16., Journal of the Chemical Society Perkin Transactions 1, 1981, p2786 - 2799 Journal Article, 1981

H. Wagner, B. O'Donnell, D. M. X. Donnelly and M. J. Meegan., Structure of a new 4-Phenylbenzopyran-2-one from Pityrogramma calomelanos., Tetrahedron Letters, 1979, p4269 - 4273 Journal Article, 1979

A. R. Battersby, C. J. Fookes, E. McDonald and M. J. Meegan., Biosynthesis of Type III Porphyrins., Journal of the Chemical Society Chemical Communications , 1978, p185 - 186 Journal Article, 1978

P.J. Gunning, P. Kavanagh, M. J. Meegan and D. M. X. Donnelly., Reactions of 6a, 11a-dihydro-6H-benzofuro[3,2-c][1]benzopyrans., Journal of the Chemical Society Perkin Transactions 1, 1977, p691 - 694 Journal Article, 1977

Non-Peer-Reviewed Publications

Cormac A. O'Donohoe, Andrew S. Knox, and Mary J. Meegan, Antiproliferative and physiological stability studies , 2006All Ireland Schools of Pharmacy 28th Research Seminar, Queens University Belfast, April 10-11, 2006, 2006, ppP14- Conference Paper, 2006

Thomas Greene, Tom McCabe and Mary J Meegan, , The b- {Lactam ring as a scaffold for combretastatin A-4 analogues , 15th Conference of GP2A, University of Bath, , Bath, UK , September 7-8, 2006,, 2006, ppP16- Meeting Abstract, 2006

Jason Horan and Mary J Meegan, Synthesis of a series of 1,2,3,4-tetrahydroisoquinoline analogues for use as selective estrogen receptor modulators,, 15th Conference of GP2A, University of Bath, Bath, UK, September 7-8, 2006, 2006, ppP19- Meeting Abstract, 2006

I.M. Barrett, M.J Meegan, D. M.Zisterer., Synthesis and Biochemistry of Some Novel Estrogen Receptor Antagonists , 2006All Ireland Schools of Pharmacy 28th Research Seminar , Queens University Belfast, April 10-11, 2006, 2006, pp12- Conference Paper, 2006

N.O. Keely, M.J. Meegan, Design, synthesis and evaluation of dual acting estrogen receptor conjugates, 2006All Ireland Schools of Pharmacy 28th Research Seminar, Queens University Belfast, April 10-11, 2006, 2006, pp40- Conference Paper, 2006

M.J.Meegan, , Design, synthesis and biochemical studies of novel estrogen receptor antagonists; , 15th Conference of GP2A, University of Bath, , Bath, UK, September 7-8, 2006,, 2006, ppI-4 Meeting Abstract, 2006

Niall O. Keely and Mary J Meegan,, Design and Synthesis and evaluation of dual acting estrogen receptor antagonist conjugates, Recent Advances in Synthesis and Chemical Biology, Royal College of Surgeons in Ireland, Dublin, December 15th, 2006,, 2006, ppP4- Meeting Abstract, 2006

Thomas F. Greene, Thomas McCabe, Mary J. Meegan., The â-Lactam Ring as a Scaffold for Combretastatin A-4 Analogues, 2006All Ireland Schools of Pharmacy, 28th Research Seminar, Queens University Belfast, April 10-11, 2006, 2006, ppP52- Conference Paper, 2006

Jason Horan and Mary J. Meegan, Synthesis and characterisation of 1,2,3,4-tetrahydroisoquinolines:, 2006All Ireland Schools of Pharmacy28th Research Seminar, Queens University Belfast, April 10-11, 2006, 2006, ppP24- Conference Paper, 2006

Jason Horan and Mary J Meegan, Synthesis of a series of 1,2,3,4-tetrahydroisoquinoline analogues for use as selective estrogen receptor modulators, , Recent Advances in Synthesis and Chemical Biology, Royal College of Surgeons in Ireland, , Dublin, December 15th, 2006, ppP13- Meeting Abstract, 2006

Thomas Greene, Tom McCabe and Mary J Meegan, The b-Lactam ring as a scaffold for combretastatin A-4 analogues , , Recent Advances in Synthesis and Chemical Biology, Royal College of Surgeons in Ireland, Dublin, December 15th, 2006,, 2006, ppP31- Meeting Abstract, 2006

Niall O.Keely and Mary J Meegan, Design and Synthesis and evaluation of dual acting estrogen receptor antagonist conjugates, 15th Conference of GP2A, University of Bath,, Bath, UK, September 7-8, 2006, 2006, ppP23- Meeting Abstract, 2006

Jason Horan and Mary J. Meegan , Synthesis of a series of 1,2,3,4 -Tetrahydroisoquinoline Analogues :, Recent Advances in Synthesis and Chemical Biology IV, University College Dublin , , 2nd December 2005, 2005, ppP67- Conference Paper, 2005

Andrew Knox, Mary Meegan, Vlavimir Sobolev, Dermot Frost, David Lloyd, Development, refinement and validation of a novel vHTS protocol for ER alpha antagonists, Biomolecular Simulations - From Prediction to Practice: MGMS International Meeting 2005, Trinity College Dublin , 11-14 September 2005, 2005 Conference Paper, 2005

Georgia Golfis, Andrew J.S. Knox, Mary J. Meegan, , Charting Cancer Medicinal Chemistry Space, Recent Advances in Synthesis and Chemical Biology IV, University College Dublin , 2nd December 2005, 2nd December 2005, 2005, ppP39- Conference Paper, 2005

Claire M. Gorry, Andrew S. Knox, Cormac A. O'Donohoe and Mary J. Meegan, ANTIPROLIFERATIVE AND PHYSIOLOGICAL STABILTY STUDIES OF NOVEL 1,4-DIHYDROPYRIDINES, Recent Advances in Synthesis and Chemical Biology IV, University College Dublin ,, 2nd December 2005, 2005, ppP62- Conference Paper, 2005

Andrew J.S. Knox, Mary J. Meegan, Vladimir Sobolev, Dermot Frost, David G. Lloyd, Development, refinement and validation of a novel vHTS protocol for ER alpha antagonists, Recent Advances in Synthesis and Chemical Biology IV,, University College Dublin , 2nd December 2005, 2005, ppP60- Conference Paper, 2005

Niall O. Keely and Mary J. Meegan, Design, synthesis and biochemistry of dual acting estrogen receptor conjugates - synthesis and antiestrogenic effects in human breast cancer cells, Recent Advances in Synthesis and Chemical Biology IV , University College Dublin , 2nd December 2005, 2nd December 2005, 2005, ppP75- Conference Paper, 2005

Thomas F. Greene, Mary J. Meegan., The â-Lactam Ring as a Scaffold for Combretastatin A-4 Analogues, Recent Advances in Synthesis and Chemical Biology IV, University College Dublin , , 2nd December 2005, 2005, ppP32- Conference Paper, 2005

Andrew Knox, Mary J.Meegan, Dermot Frost , James C. Sexton, David G. Lloyd, Validation of a new virtual high throughput screening protocol for estrogen receptor antagonists, Reaction Mechanisms VII, University College Dublin, 4-8 July, 2004 Conference Paper, 2004

Andrew S Knox, Mary J Meegan, Dermot Frost, Daniela M. Zisterer, David G. , Identification of anticancer agents with 'Forward-Reverse' virtual high throughput , 228th ACS meeting, PHILADELPHIA, 22-26-AUG-2004, 2004 Conference Paper, 2004

Andrew Knox, Mary Meegan, Dermot Frost, David Lloyd, "Identification of novel anticancer agents with 'Forward-Reverse' virtual high throughput screening (Effect of Database pre-processing)", Young Modellers Forum, LONDON, 3-DEC-2004, 2004 Conference Paper, 2004

Andrew Knox , Mary Meegan , Dermot Frost , David Lloyd, Ligand pre-processing in virtual screening - the impact of database preparation on hit retrieval, ECHEMINFO, ONLINE, 8-19-DEC-2004, 2004 Conference Paper, 2004

Miriam Carr, Mary J. Meegan, D. M. Zisterer, Cytotoxic β-Lactams: synthesis and antiproliferative effects, Recent Advances in the Synthesis and Chemical Biology III, Centre for Synthesis and Chemical Biology, Trinity College Dublin, 13 December, 2004 Conference Paper, 2004

Irene M. Barrett and Mary J Meegan, Mechanism of Action of Non-isomerisable Estrogen Receptor Modulators, Reaction Mechanisms VII, University College Dublin, 4-8 July, 2004 Conference Paper, 2004

Mary J. Meegan, D. M. Zisterer, Irene M. Barrett, Non-isomerisable Estrogen Receptor Modulators:Potential for the Treatment of Breast Cancer, Recent Advances in the Synthesis and Chemical Biology III, Centre for Synthesis and Chemical Biology, Trinity College Dublin, 13 December, 2004 Conference Paper, 2004

A.S.Knox, M.J.Meegan, D.Frost, D.M.Zisterer and D.G.Lloyd, Identification of novel anticancer agents with "Forward-Reverse" virtual high throughput screening, Cancer Drug discovery. IBC's 9th Annual World Congress:Drug Discovery Technology, Boston, USA, August 8-13, 2004 Conference Paper, 2004

Andrew S Knox, Mary J Meegan, Timothy P O'Sullivan, Helena M Smith and DM Zisterer, Synthesis, Computational Modelling and Biochemical Evaluation of Novel Antiestrogens, Conway Festival of Research, University College Dublin, September, 2003, pp69 - 69 Conference Paper, 2003

SG Butler and MJ Meegan, Strategies for the design and synthesis of novel selective serotonin reuptake inhibitors, Proceedings of the twenty-fifth TCD/QUB annual joint research seminar, Trinity College Dublin, March, 2003, pp19 - 19 Meeting Abstract, 2003

Andrew S Knox, Mary J Meegan, Dermot Frost and James C Sexton, Validation and development of a virtual high-throughput screening protocol for estrogen receptor antagonists, Recent Advances in Synthesis and Chemical Biology II, Royal College of Surgeons in Ireland, December, 2003 Conference Paper, 2003

JJ Keating, MJ Meegan and D Corrigan, Impurity profiling of PMK and PK, (key ketone precursors of the amphetamine derivatives MDMA and MBDB), synthesised via the Prilazhaev route, Proceedings of the twenty-fifth TCD/QUB annual joint research seminar, Trinity College Dublin, March, 2003, pp2 - 2 Meeting Abstract, 2003

Mary J Meegan, James J Keating and Desmond Corrigan, Impurity Profiling of PMK and PEK, (key ketone precursors of the amphetamine derivatives MDMA and MBDB), synthesised via the Prilazhaev route, Recent Advances in Synthesis and Chemical Biology II, Royal College of Surgeons in Ireland, December, 2003, pp55 - 55 Conference Paper, 2003

M O'Sullivan and MJ Meegan, Investigation of a library of 1,2,3,4-tetrahydroisoquinolines and related compounds with monoamine oxidase inhibitory activity, Proceedings of the twenty-fifth TCD/QUB annual joint research seminar, Trinity College Dublin, March, 2003, pp8 - 8 Meeting Abstract, 2003

AS Knox, MJ Meegan, D Frost and JC Sexton, Development of a virtual high-throughput screening protocol for estrogen receptor antagonists, Proceedings of the twenty-fifth TCD/QUB annual joint research seminar, Trinity College Dublin, March, 2003, pp18 - 18 Meeting Abstract, 2003

Mary M O'Sullivan and Mary J Meegan, Investigation of a library of 1,2,3,4-tetrahydroisoquinolines and related compounds as dual inhibitors of monoamine oxidase and acetyl cholinesterase, Recent Advances in Synthesis and Chemical Biology II, Royal College of Surgeons in Ireland, December, 2003, pp59 - 59 Conference Paper, 2003

Miriam Carr, Mary J Meegan, Helena Smith and DM Zisterer, Beta-lactam structure as a scaffold for non-isomerisable estrogen receptor modulators - synthesis, computational modelling and antiestrogenic effects, Recent Advances in Synthesis and Chemical Biology II, Royal College of Surgeons in Ireland, December, 2003, pp57 - 57 Conference Paper, 2003

Helena M Smith, Andrew S Knox, Mary J Meegan, Timothy P O'Sullivan, and DM Zisterer, Synthesis and Biochemical evaluation of Novel Antiestrogens, Recent Advances in Synthesis and Chemical Biology II, Royal College of Surgeons in Ireland, December, 2003, pp58 - 58 Conference Paper, 2003

AS Knox, MJ Meegan, TP O'Sullivan, HM Smith and DM Zisterer, Synthesis, Computational Modelling and Biological Evaluation of Novel Antiestrogens, Recent Advances in Synthesis and Chemical Biology, University College Dublin, December, 2002, pp54 - 54 Meeting Abstract, 2002

MT Breen and MJ Meegan, Structure activity relationship study of novel monoamine oxidase inhibitors, Royal Society of Chemistry, Third International Meeting on Drugs from Natural Products, Trinity College Dublin, July, 2002, pp32 - 32 Meeting Abstract, 2002

MT Breen and MJ Meegan, Novel monoamine oxidase inhibitors (MAOIs), Recent Advances in Synthesis and Chemical Biology, University College Dublin, December, 2002, pp39 - 39 Meeting Abstract, 2002

JJ Keating, MJ Meegan, SG Butler, GG Shaw and D Corrigan, 6-Halo Derivatives of MDMA (Ecstasy) and MBDB: Synthesis and Pharmacological Activity, Recent Advances in Synthesis and Chemical Biology, University College Dublin, December, 2002, pp27 - 27 Meeting Abstract, 2002

Wei Shi, Cormac O'Donohoe and Mary J. Meegan , Synthesis and in vitro testing of Pyrazole 1, 4-Dihydropyridines for their anti-proliferative properties, Recent Advances in Synthesis and Chemical Biology VII, University College Dublin, December12th, 2008, ppP55- Meeting Abstract,

Yvonne McNamara, Suzanne Cloonan, D. Clive Williams and Mary J. Meegan,, Synthesis and Biochemical Evaluation of Novel Agents which Bind to the Serotonin Transporter (SERT) and Exhibit a Potential Chemotherapeutic Effect, Recent Advances in Synthesis and Chemical Biology VII, University College Dublin, December12th, 2008, ppP37- Meeting Abstract,

Niamh O'Boyle and Mary J. Meegan , Synthesis, Biochemical evaluation and molecular modelling studies of novel heterocyclic compounds, American Chemical Society 236th National meeting, Philadelphia, USA, 17-21 August 2008 Meeting Abstract,

Niall O. Keely and Mary J Meegan, Design, Synthesis and Biochemical Evaluation of Novel Estrogen receptor conjugates for the treatment of hormone dependent breast cancer, American Chemical Society 236th National meeting, Philadelphia, USA, 17-21 August 2008 Meeting Abstract,

Niamh O'Boyle and Mary J. Meegan, Synthesis and Biolchemical Evaluation of Heterocyclic Anti-Cancer Compounds , Recent Advances in Synthesis and Chemical Biology VII, University College Dublin, December12th, 2008, ppP60- Meeting Abstract,

Research Expertise

Description

My research interests lie in Pharmaceutical Chemistry in the rational design of new medicines, specifically in the design of highly potent and selective estrogen receptor modulators (SERMs) which may be utilised in the treatment of breast cancer and osteoporosis. Extensive molecular modelling analysis of the specific interactions between drugs such as tamoxifen and raloxifene and models of the protein target (the Estrogen Receptor) has led to the design and synthesis of novel structurally modified estrogen receptor modulators with altered selectivity and affinity for the protein receptor. Ongoing research themes examine the relationship between structure and antiproliferative activity of these products against MCF-7 breast cancer cells, and may lead to a better understanding of the specific structural requirements for estrogen receptor agonist and antagonist activity. This research work is carried out in collaboration with Dr. D. Zisterer and Professor Clive Williams in the School of Biochemistry and Immunology, Trinity College Dublin. Related research interests include the investigation of the mechanism of action of novel cytotoxic heterocycles against breast cancer cell lines (both ER+ and ER-) and CLL(Chronic lymphocytic leukaemia) and the development of virtual high throughput screening computational methodologies for the identification of new anticancer molecular scaffolds. In addition, we have extensive expertise in the area of impurity profiling of amphetamines and related ecstasy type drugs of abuse and also have established current research projects involving the design and evaluation of novel selective serotonin reuptake inhibitors.

Projects

  • Title
    • Design, synthesis and evaluation of heterocyclic derivatives of 3,4,5-trimethoxystyrene as microtubule binding agents
  • Summary
    • This research project will examine the molecular design, chemistry and biochemical activity of some heterocyclic derivatives of 3,4,5-trimethoxystyrene as microtubule binding agents, with potential therapeutic use as anticancer agents in breast cancer. Advances in breast cancer research have established the existence of clinical disease sub-types, each with distint pathologies, course of disease progression and response to therapeutic intervention. Survival outcomes have increased dramatically in recent years for estrogen receptor(ER) positive disease largely due to the routine use of the antiestrogen tamoxifen or aromatase inhibitors such as anastrazole. However, significant disease subtypes such as "triple negative " breast tcancer (lacking expression of ER, progesterone or HER-2 receptor; approx 15% of cases) present a difficult challemge with standard chemotherapy having little impact on overall survival. Treatment of HER-2 positive breast cancer, a sub-type characterised by frequent metastatic progression is also clinically challenging although agents such as the moniclonal antibody trastuzumab have proved very useful. There is an ongoing clinical requirement for the identification of more targeted and selective agents as potential breast cancer drugs for the various breast cancer groups. Microtubule binding agents (MBAs) are an important category of anticancer drugs aiming to inhibit the assembly of tubulin to microtubules or the disassembly of microtubules to tubulin, thus blocking the cell division. Among all the natural products that possess such mechanism of action, colchicine and combretastatin A-4 have driven the interest of many research groups, due to their structural simplicity and antiproliferative activities. This project will focus on the design of heterocyclic amide derivatives of combretastatin A-4. The compounds identified for synthesis in this research group are a new series of heterocyclic derivatives of the 3,4,5-trimethoxystyrene scaffold having increased water solubility, and therefore are very suitable chemical scaffolds for development as potential biologically active compounds.
  • Date From
    • September 2013
  • Date To
    • September 2017
  • Title
    • Design and evaluation of novel molecules to target chronic lymphocytic leukaemia (CLL)
  • Summary
    • Cancers of the lymphatic cells (lymphomas) account for approximately 12% of malignant diseases worldwide and 80% of these cases are subdivided into non-Hodgkin's lymphomas (NHL). As part of an ongoing research project we have sought to identify possible alternatives to the current clinical drugs used in the treatments for chronic lymphocytic leukaemia(CLL). We have recently discovered structural derivatives of the anti-depressant drug maprotiline which are effective against Burkitt's lymphoma and related lymphomas and are potential new targets for the design of compounds with activity against chronic lymphocytic leukaemia(CLL). We have previously demonstrated that a series of these maprotiline related 9,10-ethanoanthracenes express significant antiproliferative effects in vitro in two BL cell lines: EBV- MUTU-I and the chemoresistant EBV+ DG75 lymphoma cell lines. The objective of this project is the design and evaluation of novel small molecules which target chronic lymphocytic leukaemia(CLL). Based on our previous studies, a small focussed library of structurally related anthracene and related compounds will be designed and chemically characterised. Many of these compounds contained a classic nitrostyrene or unsaturated ketone core which have also been previously shown to possess activity in the Burkitt lymphoma cell lines. In this project the structures proposed for investigation are based on the anthracene and related ethano-anthracene scaffolds. These compounds will be synthesised via a number of established routes and each compound will be subsequently characterised by spectroscopic methods (1H and 13C NMR, IR and HRMS). The antiproliferative activities of the compounds will be evaluated using two EBV-transformed CLL cell lines PGA and HG3. A possible mechanism of action for the compounds will be investigated. The structure activity relationships for the series of products will also be examined.
  • Date From
    • September 2015
  • Date To
    • September 2019
  • Title
    • New targets for old drugs: Development of novel -lactams with anticancer activity
  • Summary
    • This project will examine the chemistry and biochemical activity of novel fluorinated -lactam molecules and will assess their potential anticancer activity. Naturally occurring and synthetic β-lactams (azetidin-2-ones) are best known for their potent antibacterial activities. Molecules containing the azetidinone (β-lactam) heterocycles have also been demonstrated to have additional alternative potent and interesting activities, and occupy a central place among medicinally important compounds. Examples of the azetidin-2-one scaffold have recently been investigated as cytotoxic agents and as inhibitors of proteases such as leukocyte elastase, gelatinases and tryptases. Many nitrogen containing heterocyclic compounds e.g thiazoles, pyrroles, indoles etc. have been designed as tubulin targetting agents which bind to tubulin and disrupt mitosis in cancer cells. We have previously demonstrated that the azetidin-2-one(β-lactam) ring structure can be modified to result in compounds with potent antitumour activity in a wide range of cancer cell lines, e.g. breast, lung, prostate and leukaemia cell lines. These compounds also result in cell cycle arrest at the G2/M phase. In this project, the use of the four-membered nitrogen heterocycle azetidin-2-one (β-lactam) ring as a scaffold for bioactive compounds is investigated in an effort to gain access to novel therapeutic agents that possess vascular targeting and potent anticancer effects in tumour cells. The specific effects on biological activity of the introduction of a fluorine substituent on the azetidinone scaffold will be investigated to optimise the potency of selected examples.
  • Date From
    • 2015
  • Date To
    • 2017
  • Title
    • b-Lactam analogues of combretastatin A-4 prevent metabolic inactivation by glucuronidation in chemoresistant HT-29 colon cancer cells
  • Summary
    • Glucuronidation by uridine 5-diphosphoglucuronosyl transferase enzymes (UGTs) is a cause of intrinsic drug resistance in cancer cells. Glucuronidation of combretastatin A-4 (CA-4) was previously identified as a mechanism of resistance in hepatocellular cancer cells. In the project we propose chemical manipulation of b- lactam bridged analogues of Combretastatin A-4 as a novel means of overcoming drug resistance associated with glucuronidation due to the expression of UGTs in the CA-4 resistant human colon cancer HT-29 cells. The alkene bridge of CA-4 is replaced with a b-lactam ring to circumvent potential iso- merisation while the potential sites of glucuronate conjugation are deleted in the novel 3-substituted- 1,4-diaryl-2-azetidinone analogues of CA-4. We hypothesise that glucuronidation of CA-4 is the mech- anism of drug resistance in HT-29 cells. Ring B thioether containing 2-azetidinone analogues of CA-4 such as 4-(4-(methylthio)phenyl)-3-phenyl-1-(3,4,5-trimethoxyphenyl)azetidin-2-one (27) and 3- hydroxy-4-(4-(methylthio)phenyl)-1-(3,4,5-trimethoxyphenyl)azetidin-2-one (45) were identified as the most potent inhibitors of tumour cell growth, independent of UGT status, displaying antiproliferative activity in the low nanomolar range. These compounds also disrupted the microtubular structure in MCF- 7 and HT-29 cells, and caused G2/M arrest and apoptosis. Taken together, these findings highlight the potential of chemical manipulation as a means of overcoming glucuronidation attributed drug resistance in CA-4 resistant human colon cancer HT-29 cells, allowing the development of therapeutically superior analogues.
  • Funding Agency
    • King Abdul Aziz University - Jeddah, Saudi Arabia
  • Date From
    • 2012
  • Date To
    • 2017

Keywords

Amphetamines; Anticancer Drug Design; Antiestrogens; Carbapenem antibiotics; Chemistry of drug metabolism; Chemistry of drug receptor interactions; Design and synthesis of drugs; Drug development; Molecular modelling of Estrogen Receptor antagonists; Pharmacologically active heterocycles

Recognition

Representations

Guest Editor of Current Topics in Medicinal Chemistry 2005/2006

Awards and Honours

Royal Commission 1851 Overseas Postdoctoral Fellowship 1976

Hugh Ryan Gold Medal in Chemistry, University College Dublin 1973

Memberships

Member of the Royal Society of Chemistry 1977 – Present

Member of the American Chemical Society 1997 – Present

Member of the Society of the Chemical Industry Chartered Chemist 1990 – Present