ABSTRACT
Guanylthiourea (GTU) derivatives were identified as possible anti-malarial agents, recently, using in vitro studies on Plasmodium falciparum. This article gives an account of the in vivo anti-malarial activity of GTU derivatives against experimental rodent malaria. A total of 20 synthesized GTU derivatives were evaluated for in vivo antimalarial activity, out of which six showed encouraging results; one compound appeared to have curative potential. Molecular docking and molecular dynamics analysis were carried out to understand the molecular level interactions.
Subject(s)
Antimalarials/pharmacology , Guanylthiourea/pharmacology , Malaria/drug therapy , Plasmodium falciparum/drug effects , Antimalarials/chemical synthesis , Antimalarials/chemistry , Dose-Response Relationship, Drug , Guanylthiourea/chemical synthesis , Guanylthiourea/chemistry , Models, Molecular , Molecular Structure , Parasitic Sensitivity Tests , Structure-Activity RelationshipABSTRACT
A new class of compounds based on S-benzylated guanylthiourea has been designed as potential PfDHFR inhibitors using computer aided methods (molecular electrostatic potential, molecular docking). Several compounds in this class have been synthesized starting from guanylthiourea and alkyl bromides. In vitro studies showed that two compounds from this class are active with the IC50 value of 100 µM and 400 nM.
