Synthesis and In Vitro Antitumor Evaluation of Some Carbazole-Based Thiazole, Thiophene, and 1,3,4-Thiadiazole Derivatives

Abstract

In continuation to our efforts to discover new powerful antitumor agents, a series of new carbazole-based thiazole, thiophene, and 1,3,4-thiadiazole derivatives were conveniently synthesized, spectrally characterized, and mechanistically discussed. The synthetic strategy involves the cyclization reactions of two easily attainable commencing materials, N-(9-ethylcarbazol-3-yl)-2-cyanoacetamide (1) and 2-((9-ethylcarbazol-3-yl)hydrazono)-3-oxo-N-phenylbutanethioamide (20), with α-chlorocarbonyl reagents, α-chloronitrile, and hydrazonoyl chlorides in a basic medium. They were also assessed against three human tumor cell lines (HCT-116, HepG-2, and MCF-7) and one non-tumor human cell line (REP1) for their in vitro antitumor activity. The results demonstrated that seven carbazoles 4, 15 a, 15 b, 15 d, 20, 22 b, and 29 a had high antitumor activity, having IC50 values in the range 5.24–9.70 μM. The most potent carbazoles 15 b, 20 and 22 b inhibited the growth of all tested tumor cell lines and did not display human toxicity.