Abualhasan, Murad N. and Good, James A. D. and Wittayanarakul, Kitiyaporn and Anthony, Nahoum G. and Berretta, Giacomo and Rath, Oliver and Kozielski, Frank and Sutcliffe, Oliver B. and Mackay, Simon P. (2012) Doing the methylene shuffle - further insights into the inhibition of mitotic kinesin Eg5 with S-trityl L-cysteine. European Journal of Medicinal Chemistry, 54. pp. 483-498. ISSN 0223-5234Full text not available in this repository. (Request a copy from the Strathclyde author)
S-Trityl L-cysteine (STLC) is an inhibitor of the mitotic kinesin Eg5 with potential as an antimitotic chemotherapeutic agent. We previously reported the crystal structure of the ligand protein complex, and now for the first time, have quantified the interactions using a molecular dynamics based approach. Based on these data, we have explored the SAR of the trityl head group using the methylene shuffle strategy to expand the occupation of one of the hydrophobic pockets. The most potent compounds exhibit strong (<100 nM) inhibition of Eg5 in the basal ATPase assay and inhibit growth in a variety of tumour-derived cell lines. (C) 2012 Elsevier Masson SAS. All rights reserved.
|Keywords:||methylene shuffle , insights, inhibition, mitotic kinesin Eg5 with S-trityl L-cysteine , Pharmacy and materia medica, Organic Chemistry, Drug Discovery, Pharmacology|
|Subjects:||Medicine > Pharmacy and materia medica|
|Department:||Faculty of Science > Strathclyde Institute of Pharmacy and Biomedical Sciences|
|Depositing user:||Pure Administrator|
|Date Deposited:||07 Dec 2012 15:25|
|Last modified:||07 Jan 2017 01:41|