3D-QSAR Study of Human DHFR Inhibitors Based on GRIND Descriptors and Designing of New Inhibitors

Dihydrofolate reductase (DHFR), an indispensable enzyme in the folate metabolism, converts dihydrofolate (DHF) to tetrahydrofolate (THF) in the presence of NADPH found in all organisms and regulates the level of THF in the cell. DHFR has been a validated drug target for the development of therapeutics for human cancer for decades [1]. Hence, there is an urgent need to identify and develop new inhibitors with high potency and selectivity relative to a specific species of DHFR. In this regard, 3D-QSAR modeling is one of the powerful computational methods employed in medicinal chemistry for deciding about the structure-activity relationship of new chemical compounds. In the present study, we studied a data set including 2, 4-diaminopyrimidine scaffold with the acetylenic linker to another substituted aryl ring with human DHFR receptor for 3D-QSAR modeling.