Rationale design, synthesis, cytotoxicity evaluation, and in silico mechanistic studies of novel 1,2,3-triazoles with potential anticancer activity

Abstract

A new set of 1,2,3-triazoles was designed and synthesized to evaluate their potential to inhibit the growth of cancer cells. Thiazole, thiazolone, and hydrazine as effective fragments present in certain anticancer molecules were incorporated in the structure of the new molecules given that they have been suggested to enhance the cytotoxic activity. The growth inhibition (GI) of all the compounds was evaluated by the National Cancer Institute against a panel of sixty human cancer cells of nine different types. Three compounds showed mild to moderate growth inhibition activity against lung, renal, and prostate cancerous cells. The best GI activity was observed for triazole derivative 14 against EKVX, RXF-393, and UO-31 with GI of 37.59%, 33.76%, and 29.49%, respectively. Additionally, thiazolone-linked triazole derivative 21 exhibited relatively good activity with GI of 28.89%, 32.87%, and 22.26% against HOP-92, RXF-393, and UO-31, respectively. Additionally, docking and pharmacokinetic profiling studies were performed to examine the probable mechanistic effect of these cytotoxic derivatives and evaluate their potential as good drug candidates.