Design, and synthesis of selectively anticancer 4-cyanophenyl substituted thiazol-2-ylhydrazones. Issue 52 (28th November 2022)

• Record Type: Journal Article
• Authors: Mehmood, Hasnain; Musa, Mustapha; Woodward, Simon; Hossan, Md Shahadat; Bradshaw, Tracey D.; Haroon, Muhammad; Nortcliffe, Andrew; Akhtar, Tashfeen
• Is Part Of: RSC advances. Volume 12:Issue 52(2022)
• Page Start: 34126
• Page End: 34141
• Publication Date: 2022-11-28
• Subjects: Chemistry -- Periodicals; 540.5
• DOI: 10.1039/d2ra03226k
• Languages: English
• ISSNs: 2046-2069

Abstract

Abstract : Cyclization of substituted thiosemicarbazones with α-bromo-4-cyanoacetophenone allows rapid single-step sustainable syntheses of 4-cyanophenyl-2-hydrazinylthiazoles libraries (30 examples, 66–79%). Abstract : Cyclization of substituted thiosemicarbazones with α-bromo-4-cyanoacetophenone allows rapid single-step sustainable syntheses of 4-cyanophenyl-2-hydrazinylthiazoles libraries (30 examples, 66–79%). All show anticancer efficacy against HCT-116 and MCF-7 carcinoma cell lines with the majority being more active than cisplatin positive controls. The compounds 2-(2-(2-hydroxy-3-methylbenzylidene)hydrazinyl)-4-(4-cyanophenyl)thiazole (3f ) and 2-(2-((pentafluorophenyl)methylene)-hydrazinyl)-4-(4-cyanophenyl)thiazole (3a′ ) show optimal GI50 values (1.0 ± 0.1 μM and 1.7 ± 0.3 μM) against MCF-7 breast cancer cells. Against colorectal carcinoma HCT-116 cells, (2-(2-(3-bromothiophen-2-yl)methylene)hydrazinyl)-4-(4-cyanophenyl)thiazole (3b′ ), 2-(2-(2-hydroxy-3-methylbenzylidene)hydrazinyl)-4-(4-cyanophenyl)thiazole (3f ), 2-(2-(2, 6-dichlorobenzylidene)hydrazinyl)-4-(4-cyanophenyl)thiazole (3n ) and 2-(2-(1-(4-fluorophenyl)ethylidene)hydrazinyl)-4-(4-cyanophenyl)thiazole (3w ) are the most active (GI50 values: 1.6 ± 0.2, 1.6 ± 0.1, 1.1 ± 0.5 and 1.5 ± 0.8 μM respectively). Control studies with MRC-5 cells indicate appreciable selectivity towards the cancer cells targeted. Significant ( p < 0.005) growth inhibition and cytotoxicity effects for the thiazoles 3 were corroborated by cell count and clonogenic assays using the same cancer cell lines at 5 and 10 μM agent concentrations. Cell cycle, caspase activation and Western blot assays demonstrated that compounds 3b′ and 3f induce cancer cell death via caspase-dependent apoptosis. The combination of straight forward synthesis and high activity makes the thiazoles 3 an interesting lead for further development.