SYNTHESIS, IN VITRO BIOLOGICAL AND COMPUTATIONAL EVALUATION OF SOME NOVEL PYRAZOLES AS POTENTIAL ANTICANCER AGENTS

The major challenge in modern drug discovery has been the design and development of new anticancer drugs with improved efficacy and minimal side effects, especially due to a rapid rise in multidrug resistant tumors. In the recent past, United States Food & Drug Administration (US FDA) newly approved anticancer drug Crizotinib (Xalkori) possess a pyrazole nucleus as core moiety. Therefore in the present investigation, we have synthesised a series of pyrazoles KVP, KVP1-4 and evaluated their potential as anticancer agents by using in vitro brine shrimp (Artemia salina) cytotoxicity bioassay. Among the compounds tested, compound KVP2 has showed signifcant cytotoxicity at ED50 value 5.43 ± 0.16 microgram/mL. Consequently, in silico molecular docking studies have also been performed to evaluate the possible underlying mechanism of action of KVP and KVP1-4 against DHFR (Dihydrofolate reductase) anticancer drug target. Molecular docking results revealed that the KVP and KVP1-4 is less selective towards inhibition of DHFR. Keywords: Cancer, US FDA, Pyrazole, Brine shrimp lethality, Molecular docking, Dihydrofolate reductase (DHFR)