Synthesis, characterization, and anticancer evaluation of novel 4‐hydrazinothiazole analogs

Abstract

AbstractSingle‐step synthesis of novel 4‐hydrazinothiazole derivatives 6a–e was achieved under mild conditions using the sequential four‐components method involving isothiocyanate, aminoguanidine, carbonyl adduct, and α‐haloketone derivatives. Deprotection of these hydrazinothiazoles was influenced by acylation, providing a novel group of diacylated molecular structures with a broader scope for the design of thiazolyl‐containing drugs 7a and 7b. FTIR, 1H/13C NMR, LC–MS spectroscopy, and CHN elemental analyses were used to study the compound chemical structures. Using a 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide (MTT) assay on human periodontal ligament fibroblast (HPDLF) cells, the 4‐hydrazinothiazole derivatives were screened for cytotoxicity in an in vitro cytotoxicity investigation. The 4‐hydrazinothiazole compound 6b bearing an isopropylidene‐hydrazino group demonstrated strongly potent cytotoxicity against CAKI1 (IC50 = 1.65 ± 0.24 μM) and A498 (IC50 of 0.85 ± 0.24 μM). Furthermore, the chloroacetyl‐containing thiazole compound 7a displayed efficient inhibition of growth against the test cell lines CAKI1 and A498 at low micromolar concentrations, IC50 0.78 and 0.74 μM, respectively.