Thymidylate synthase (TS) is a crucial enzyme that catalyzes the reductive methylation of 2'-deoxyuridine-5'-monophosphate to 2'-deoxythymidine-5'- monophosphate. Inhibition of TS has been an attractive strategy in the development of agents against cancer. Though the dihydrofolate reductase of pathogens such as Toxoplasma gondii (tg) have been attractive targets, TS from tg (tgTS) is a potential novel target for inhibition to treat T. gondii infections. We have previously published the design, synthesis and biological evaluation of pyrrolo[2,3-d]pyrimidines and thieno[2,3-d]pyrimidines as potent inhibitors of human (hTS) and tgTS. A dataset of 85 inhibitors reported from our laboratory was used to develop 3D QSAR models that correlate chemical structure and inhibitory potency for hTS and tgTS using CoMFA. The details of these models, their predictive power and their utility to explain selectivity for hTS and tgTS will be reported.

CoMFA analysis of 6-5 bicyclic inhibitors of human and <i>Toxoplasma gondii </i>thymidylate synthase

244th National Meeting (2012)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.

CoMFA analysis of 6-5 bicyclic inhibitors of human and Toxoplasma gondii thymidylate synthase