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Design, and synthesis of selectively anticancer 4-cyanophenyl substituted thiazol-2-ylhydrazones

Mehmood, Hasnain; Musa, Mustapha; Woodward, Simon; Hossan, Md Shahadat; Bradshaw, Tracey D.; Haroon, Muhammad; Nortcliffe, Andrew; Akhtar, Tashfeen

Design, and synthesis of selectively anticancer 4-cyanophenyl substituted thiazol-2-ylhydrazones Thumbnail


Hasnain Mehmood

Mustapha Musa

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Professor of Synthetic Organic Chemistry

Md Shahadat Hossan

Muhammad Haroon

Tashfeen Akhtar


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-2yl)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 (3f) 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.


Mehmood, H., Musa, M., Woodward, S., Hossan, M. S., Bradshaw, T. D., Haroon, M., …Akhtar, T. (2022). Design, and synthesis of selectively anticancer 4-cyanophenyl substituted thiazol-2-ylhydrazones. RSC Advances, 12(52), 34126-34141.

Journal Article Type Article
Acceptance Date Nov 18, 2022
Online Publication Date Nov 28, 2022
Publication Date Nov 28, 2022
Deposit Date Dec 20, 2022
Publicly Available Date Dec 20, 2022
Journal RSC Advances
Print ISSN 2046-2069
Electronic ISSN 2046-2069
Publisher Royal Society of Chemistry (RSC)
Peer Reviewed Peer Reviewed
Volume 12
Issue 52
Pages 34126-34141
Keywords General Chemical Engineering; General Chemistry
Public URL
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