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  Strathclyde Institute of Pharmacy and Biomedical Sciences

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Prof Simon Mackay

Professor of Medicinal Chemistry

SIBS 401M

simon.mackay@strath.ac.uk

Tel : +44(0)141 548 2866 (Ext. 2866)

Molecular Modelling and Drug Design

The molecular modelling group is now firmly established within the department after its introduction in November 2000, having secured funding from industrial, research council and charitable sources. We have a suite of SGI and PC workstations for high- demand calculations in a dedicated modelling laboratory. Modelling software is used by the group to rationally design new drug prototypes against a variety of cellular targets (enzymes, receptors or nucleic acids).

Both de novo drug design and in silico screening of databases provide leads for new ligands. Newly designed molecules are synthesised by the group or by our collaborators in other academic institutions, and the compounds are assessed for activity against the target for which they have been designed. The approach is an iterative process, whereby results from activity testing are fed back into the modelling programme in order to optimise activity.

The group is currently working in the following areas: design, synthesis and evaluation of inhibitors of Leishmania species; NMR and molecular modelling studies of lexitropsin complexes with nucleic acids in order to design and synthesise new, sequence-specific DNA binding agents; design, synthesis and evaluation of selective inhibitors of protein tyrosine kinases and protein tyrosine phosphatases; molecular modelling of polypropylenemine dendrimer interactions with nucleic acids; design and synthesis of telomerase inhibitors; elucidation of the mechanism of action of the benzo[c]phenanthridine alkaloids; the design and synthesis of antituberculosis agents.


Exploring the minor groove of DNA [5.5Mb .avi]

 

 


Selected Publications

  • D.R. Adams, A. Abraham, J. Asano, C. Breslin, C.A.J. Dick, U. Ixkes, B.F. Johnston, D. Johnston, J. Kewnay, S.P. Mackay, S.J. MacKenzie, M. McFarlane, L. Mitchell, D. Spinks and Y. Takano (2007) "2-Aryl-3,3,3-trifluoro-2-hydroxypropionic acids: a new class of protein tyrosine phosphatase 1B inhibitor."   Bioorg. Med. Chem. Lett. (in press)

  • Anthony NG, Breen D, Clarke J, Donoghue G, Drummond AJ, Ellis EM, Gemmell CG, Helesbeux JJ, Hunter IS, Khalaf AI, Mackay SP, Parkinson JA, Suckling CJ, Waigh RD. (2007) "Antimicrobial lexitropsins containing amide, amidine, and alkene linking groups."   J Med Chem. 50 6116-25

  • Anthony, N., Breen, D., Clarke, J., Donoghue, G., Drummond, A., Ellis, E., Gemmell, C., Helesbeux,J-J., Hunter, I., Khalaf, A., Mackay, S., Parkinson, J., Suckling, C., Waigh, R. (2007) "Antimicrobial lexitropsins with amide, amidine, and alkene links."   J. Med. Chem. (in press)

  • G.J. Schad, A. Allanson, S.P. Mackay, A. Cannavan and J.N.A. Tettey (2007) "Development and validation of an improved HPLC method for the control of potentially counterfeit isometamidium products."   J. Pharm. Biomed. Anal. (in press)

  • Clark R.L, Deane F.M, Anthony N.G, Johnston B.F, McCarthy F.O, Mackay S.P. (2007) "Exploring DNA topoisomerase I inhibition by the benzo[c]phenanthridines fagaronine and ethoxidine using steered molecular dynamics."   Bioorg. Med. Chem. 15 4741-4752

  • R.L. Clark, K.C. Carter, A.B. Mullen, G.D. Coxon, G. Owusu-Dapaah, E. McFarlane, M.D. Duong Thi, M.H.Grant, J.N.A. Tettey and S.P. Mackay (2007) "Identification of the benzodiazepines as a new class of antileishmanial agent"   Bioorg. Med. Chem. Lett. 17 624-627

  • R.L. Clark, B.F. Johnston, C.J. Suckling and S.P. Mackay (2006) "A modelling study of a non-concerted hydrolytic cycloaddition reaction by the catalytic antibody H11."   Bioorg. Med. Chem. 14(8) 2674-83

  • V. Bhowruth, A.K. Brown, R.C. Reynolds, G.D. Coxon, S.P. Mackay, D.E. Minnikin, G.S. Besra (2006) "Symmetrical and unsymmetrical analogues of isoxyl; active agents against Mycobacterium tuberculosis."   Bioorg. Med. Chem. Lett. 16 4743-4747

  • G. Huchet, M.R, Euerby, S.P. Mackay and R.D. Waigh (2006) "The role of water in drug-receptor interactions."   J. Enz. Inhib. Med. Chem. 21 271-276

  • Nyangulu JM, Hargreaves SL, Sharples SL, Mackay SP, Waigh RD, Duval O, Mberu EK, Watkins WM. (2005) "Antimarial benzo[c]phenanthridines"   Bioorg. Med. Chem. Lett. 15 2007-2010

  • Nahoum G. Anthony, Blair F. Johnston, John A. Parkinson, Colin J. Suckling and Roger D. Waigh and Simon P. Mackay (2005) "In silico footprinting of ligands binding to the minor groove of DNA."   J. Chem. Inf. Model. 45 1896-1907

  • Nahoum G. Anthony, Keith R. Fox, Blair F. Johnston, Abedawn I. Khalaf, Simon P. Mackay, Iain S. McGroarty, John A. Parkinson, Graham G. Skellern, Colin J. Suckling and Roger D. Waigh (2004) "DNA binding of a short lexitropsin"   Bioorg. Med. Chem. Letts 14 1353-1356

  • Nahoum G. Anthony, Blair F. Johnston, Abedawn I. Khalaf, Simon P. Mackay, John A. Parkinson, Colin J. Suckling and Roger D. Waigh (2004) "Short lexitropsin that recognizes the DNA minor groove at 5’-ACATGT-3’: Understanding the role of isopropyl-thiazole."   J.A.C.S 126 11338-49

  • Khalaf AI, Ebrahimabadi AH, Drummond AJ, Anthony NG, Mackay SP, Suckling CJ, Waigh RD. (2004) "Synthesis and antimicrobial activity of some netropsin analogues"   Org Biomol Chem. 2 3119-27

  • A. Elegami, C. Bates, A.I. Gray, S.P. Mackay, G.G. Skellern, R.D. Waigh (2003) "Two very unusual macrocyclic flavonoids from the water lily Nymphaea lotus"   Phytochemistry 63 727-731

  • Donald Cairns, E. Michalitsi, Terence C. Jenkins and Simon P. Mackay (2002) "Molecular modelling and cytotoxicity of substituted anthraquinones as inhibitors of human telomerase. "   Bioorg. Med. Chem. 10 803-807

  • Bernd H. Zinselmeyer, Simon P. Mackay, Andreas G. Schatzlein and Ijeoma F. Uchegbu (2002) "The lower generation polypropylenemine dendrimers are effective gene transfer agents and relatively non-toxic"   Pharm. Res. 19 960-967

  • R.J. Anderson, D.J Bendell, M. Hooper, D. Cairns, S.P. Mackay, S.P. Hiremath, A.S. Jivanagi, S. Badami, J.S. Biradar and S. Townson (2001) "Potential transition state phosphoramidate inhibitors of b-tubulin as antifilarial agents"   J. Pharm. Pharmacol. 53 89-94

  • Michael A. Lynch, Olivier Duval, Alyona Sukhanova, Jerome Devy, Simon P. Mackay, Roger D. Waigh and Igor Nabiev (2001) "Synthesis, biological activity and comparative analysis of DNA binding affinities and human DNA topoisomerase I inhibitory activities of novel 12-alkoxybenzo[c]phenanthridinium salts"   Bioorg. Med. Chem. Lett. 11 2643-2646

  • Susan M. Hutton, Simon P. Mackay and Otto Meth-Cohn (2000) "Synthesis of benzo[i]phenanthridine and dibenzo[c,h][1,6]naphthyridine analogues of the antitumour benzo[c]phenanthridines"   Synthesis 1121-1124

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