A comprehensive review of synthesized derivatives of methotrexate in relation to their anticancer potential.

Methotrexate (MTX) is a chemotherapeutic agent with certain side effects. Efforts were made to synthesize analogues of MTX to enhance the activity and reduce side effects. Various derivatives were synthesized by structural modification of parent drug and mainly assayed for anticancer activity and binding affinity with dihydrofolatereductase (DHFR) and folylpolyglutamate synthetase (FPGS). In vitro study was carried out on cell lines CCRF. CEM, ATCC8, L. Casei, P388, L1210, L1210/R81, and H35. These synthesized derivatives have been assayed for human squamous cell carcinoma namely SSC25, SSC68, SSC78, SSC25/R1, SSC68/R1, and SSC78/R1. Some modification proved to enhance anticancer activity while others are detrimental. Some of derivatives were also tested for other biological activity like anti-malarial, anti-bacterial and anti-diabetic and show better activity. This article deals with a comprehensive overview of the synthesized derivatives by structural modifications and the impact of these modifications on its activity.