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Published on: June 23, 2019
Design, synthesis and anticancer activity of 2-arylimidazo[1,2-a]pyridinyl-3-amines
Umesh Prasad Yadav1, Arshad J Ansari2, Sahil Arora3
1Department of Human Genetics and Molecular Medicine, School of Health Sciences Central University of Punjab, Bathinda 151401, India; Department of Biochemistry, All India Institute of Medical Sciences, Patna, India.
Abstract:
A series of imido-heterocycle compounds were designed, synthesized, characterized, and evaluated for the anticancer potential using breast (MCF-7 and MDA-MB-231), pancreatic (PANC-1), and colon (HCT-116 and HT-29) cancer cell lines and normal cells, while normal cells showed no toxicity. Among the screened compounds, 4h exhibited the best anticancer potential with IC50 values ranging from 1 to 5.5 μM. Compound 4h caused G2/M phase arrest and apoptosis in all the cell lines except MDA-MB-231 mammosphere formation was inhibited. In-vitro enzyme assay showed selective topoisomerase IIα inhibition by compound 4h, leading to DNA damage as observed by fluorescent staining. Cell signalling studies showed decreased expression of cell cycle promoting related proteins while apoptotic proteins were upregulated. Interestingly MDA-MB-231 cells showed only cytostatic effects upon treatment with compound 4h due to defective p53 status. Toxicity study using overexpression of dominant-negative mutant p53 in MCF-7 cells (which have wild type functional p53) showed that anticancer potential of compound 4h is positively correlated with p53 expression.
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