Some new indole–coumarin hybrids; Synthesis, anticancer and Bcl-2 docking studies

Kamath, Pooja R and Sunil, Dhanya and Ajees, Abdul A and Paic, K S R and Das, Shubhankar (2015) Some new indole–coumarin hybrids; Synthesis, anticancer and Bcl-2 docking studies. Bioorganic Chemistry, 63. pp. 101-109.

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Hybrid molecules have attracted attention for their improved biological activity, selectivity and lesser side effects profile, distinct from their individual components. In the quest for novel anticancer drug entities, three series of indole–coumarin hybrids – 3-(1-benzyl-1H-indol-2-yl)-2H-chromen-2-ones, 2-(2-oxo-2H-chromen-3-yl)-1H-indole-3-carbaldehydes and 2-(2-oxo-2H-chromen-3-yl)-1H-indole-3-carboxylic acids were synthesized. All the synthesized compounds were characterized by spectral techniques like IR, 1H NMR, 13C NMR, mass spectrometry and elemental analysis. In silico docking studies of synthesized molecules with apoptosis related gene Bcl-2 that is recognized to play an important role in tumerogenesis were carried out. Dose-dependent cytotoxic effect of the compounds in human breast adenocarcinoma (MCF-7) and normal cell lines were assessed using MTT assay and compared with that of the standard marketed drug, Vincristine. Compound 4c had a highly lipophilic bromine substituent capable of forming halogen bond and was identified as a potent molecule both in docking as well as cytotoxicity studies. Flow cytometric cell cycle analysis of 4c exhibited apoptotic mode of cell death due to cell cycle arrest in G2/M phase. Structure activity relationship of these hybrid molecules was also studied to determine the effect of steric and electronic properties of the substituents on cell viability.

Item Type: Article
Uncontrolled Keywords: Apoptosis Cytotoxicity Indole–coumarin Bcl-2
Subjects: Engineering > MIT Manipal > Chemistry
Depositing User: MIT Library
Date Deposited: 07 Nov 2015 09:59
Last Modified: 07 Nov 2015 09:59

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