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Synthesis and biological evaluation of chalcone-linked pyrazolo[1,5-a]pyrimidines as potential anticancer agents

Abstract

A series of pyrazolo[1,5-a]pyrimidines substituted at C5 with 1-phenylprop-2-en-1-one (6a-q) and 3-phenylprop-2-en-1-one (7a-k) was synthesized and evaluated for its antiproliferative activity. Among them, 6h was found to be the most active compound with IC50 2.6 μM against the MDA-MB-231 cell line. Antiproliferative activity of this series of compounds ranged from 2.6 – 34.9 μM against A549 (lung cancer), MDA-MB-231 (breast cancer) and DU-145 (prostate cancer) cell lines. FACS analysis revealed that these hybrids arrest cell cycle at subG1 phase. Western blot analysis and immu nofluorescence assay showed the inhibition of EGFR and STAT3 axis which plays an important role in the cell survival and apoptosis. Western blot and RT-PCR analysis that displayed an increase in apoptotic proteins such as p53, p21 and Bax, and decrease in the antiapoptotic protein Bcl-2 and procaspase-9, confirmed the ability of these hybrids to trigger cell death by apoptosis. Molecular docking studies described the binding of these hybrids to the ATP binding site of EGFR.

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Publication details

The article was received on 18 Apr 2017, accepted on 13 Jul 2017 and first published on 13 Jul 2017


Article type: Research Article
DOI: 10.1039/C7MD00193B
Citation: Med. Chem. Commun., 2017, Accepted Manuscript
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    Synthesis and biological evaluation of chalcone-linked pyrazolo[1,5-a]pyrimidines as potential anticancer agents

    C. Bagul, G. K. Rao, V. K. K. Makani, J. R. Tamboli, M. P. Bhadra and A. Kamal, Med. Chem. Commun., 2017, Accepted Manuscript , DOI: 10.1039/C7MD00193B

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