Abstract

Antifolates are a class of drugs used as antibacterial, antiparasitic, and anticancer agents. This review focuses on 2-substituted-mercapto-quinazolin-4(3H)-one analogues as dihydrofolatereductase (DHFR) inhibitors. Several research work have concluded a structural model for this class of 2-thio-quinazoline derivatives to get compounds with remarkable biological activity. The pattern and orientation of the p-system substitutions with regard to the quinazoline nucleus manipulate the activity. The application of the obtained model criteria produced compounds 18, 20 and 21, which proved to be 4-8 times more active than the reference drug methotrexate (MTX, 1).

Keywords: dihydrofolatereductase (DHFR) inhibitors, 2-thioxo-quinazolin-4(3H)-one, molecular docking studies, p-system, deoxy-thymidine monophosphate(dTMP), thymidylate synthase (TS).

Graphical Abstract