Design, and synthesis of selectively anticancer 4-cyanophenyl substituted thiazol-2-ylhydrazones.
RSC Adv
; 12(52): 34126-34141, 2022 Nov 22.
Article
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| MEDLINE
| ID: mdl-36540407
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.
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01-internacional
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MEDLINE
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En
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RSC Adv
Año:
2022
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Article