Structure-activity relationship and comparative docking studies for cycloguanil analogs as PfDHFR-TS inhibitors.

ABSTRACT: Drug resistance acquired by Plasmodium falciparum (Pf) is a major problem in the treatment and control of malaria. One of the major examples of drug resistance is that caused by mutations in the active site of dihydrofolate reductase (DHFR) of Pf (PfDHFR-TS). A double mutation, A16V+S108T, is specific for resistance to the marketed drug cycloguanil. In this study, we used 58 cycloguanil (2,4-diamino-1,6-dihydro-1,3,5-triazine) derivatives to explore the relationship between various physicochemical properties and reported binding affinity data on wild-type and mutant-type A16V+S108T. Using the Hansch 2D-quantitative structure-activity relationship method, we obtained a parabolic relationship of hydrophobicity of substituents at the N1-phenyl ring with the wild-type binding affinity data. Hy

SUBMITTER: Sivaprakasam P 

PROVIDER: S-EPMC2771436 | biostudies-literature | 2009 Jul

REPOSITORIES: biostudies-literature