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Design, Synthesis and Biological Assessment of N ′-(2-Oxoindolin-3-ylidene)-6-methylimidazo[2,1- b ]thiazole-5-carbohydrazides as Potential Anti-Proliferative Agents toward MCF-7 Breast Cancer.

Authors :
Alshaye, Najla A.
Elgohary, Mohamed K.
Elkotamy, Mahmoud S.
Abdel-Aziz, Hatem A.
Source :
Pharmaceuticals (14248247); Feb2024, Vol. 17 Issue 2, p216, 17p
Publication Year :
2024

Abstract

Breast cancer is a serious threat to the health and lives of women. Two novel series of N′-(2-oxoindolin-3-ylidene)-6-methylimidazo[2,1-b]thiazole-5-carbohydrazides and 1-(aryl)-3-(6-methylimidazo[2,1-b]thiazol-5-yl)ureas were designed, synthesized and investigated for their anticancer efficacy against the MCF-7 breast cell line. Three compounds of the first series showed potent activity toward MCF-7 with IC<subscript>50</subscript> in the range 8.38–11.67 µM, respectively, as compared to Sorafenib (IC<subscript>50</subscript> = 7.55 µM). N′-(1-butyl-2-oxoindolin-3-ylidene)-6-methylimidazo[2,1-b]thiazole-5-carbohydrazide inhibited VEGFR-2 with IC<subscript>50</subscript> = 0.33 µM when compared with Sorafenib (IC<subscript>50</subscript> = 0.09 µM). Furthermore, this compound was introduced to PCR assessment, where it increased Bax, caspase 8, caspase 9 and cytochrome C levels by 4.337-, 2.727-, 4.947- and 2.420-fold, respectively, while it decreased levels of Bcl-2, as the anti-apoptotic gene, by 0.359-fold when compared to the untreated control MCF-7. This compound was also arrested in the G2/M phase by 27.07%, compared with 11.31% for the control MCF-7. Furthermore, it induced early and late apoptosis in MCF-7. In addition, a molecular docking study in the VEGFR-2 active site was performed to assess the binding profile for the most active compounds. Moreover, ADME parameters of the targeted compounds were also evaluated. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
14248247
Volume :
17
Issue :
2
Database :
Complementary Index
Journal :
Pharmaceuticals (14248247)
Publication Type :
Academic Journal
Accession number :
175651364
Full Text :
https://doi.org/10.3390/ph17020216