Synthesis and biological activities of dihydrofolate reductase inhibitors of Plasmodium falciparum

Abstract

One hundred and thirty-seven 4,6-diamino-1,2- dihydrotriazine derivatives bearing different N-1 and c-2 substituents have been synthesized and their inhibition constants (K1) against wild-type and cycloguanik resistant (16v+S108T) Dihydrofolate Reductase Enzyme from Plasmodium falciparum. The data revealed the structure-activity relationship and lead to the design of novel inhibitors, which are effective to both wild-type and mutant enzyme. A number of compounds of 4,6- diamino-1,2-dihydrotriazine derivatives were found to be potential lead compound to be developed into antimalarial agents.