Der Pharma Chemica
Journal for Medicinal Chemistry, Pharmaceutical Chemistry, Pharmaceutical Sciences and Computational Chemistry

Abstract

Design, Synthesis and Anti-proliferative Activity of Noval 1,2,4-Triazine and Pyrrolidin-2-one Derivatives

Author(s): Ankit Kumar, Umesh Kumar Singh, Faizi Muzaffar, Prateek Pathak, Praveen Kumar Tomar

1,2,4-Triazine and pyrrolidin-2-one derivatives with 1,4 substituted Salicyaldehydes were designed and synthesized in order to obtain new compounds with potential anti-proliferative activity. The structures of all synthesized compounds were confirmed by means of various spectroscopic analytical techniques. The two dimensional chemical structures of compounds were submitted to National Cancer Institute (NCI), under the Developmental Therapeutic Program (DTP). The compounds were selected for screening based on novelty, size and their physicochemical properties like log P, number of rotatable bonds, molecular weight etc. The selected samples were synthesized and send to NCI. The experimental drugs were analyzed at a single dose of 10-5 M against 60 different human tumor cancers of the lung, colon, brain, ovary, breast, prostate and kidney. Compounds TP24, PTM6 and PTM8 showed maximum activity out of all synthesized compounds. Molecular docking studies of most active compounds were also performed and revealed that they bind to podophyllotoxin binding pocket of the gamma tubulin protein.


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