Indole-coumarin-thiadiazole hybrids: An appraisal of their MCF-7 cellv growth inhibition, apoptotic, antimetastatic and computational Bcl-2 binding potential

Kamath, Pooja R and Sunil, Dhanya and Joseph, Manu M and Salam, Abdul Ajees Abdul and Sreelekha, T T (2017) Indole-coumarin-thiadiazole hybrids: An appraisal of their MCF-7 cellv growth inhibition, apoptotic, antimetastatic and computational Bcl-2 binding potential. European Journal of Medicinal Chemistry, 136 (5). pp. 442-451. ISSN 0223-5234

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Abstract

Cancer therapeutic potential of thiadiazole hybrids incorporating pharmacologically active indole and coumarin moieties have not been explored much. In the current investigation, three new thiadiazole hybrids with spacers of varying lengths linking indole and thiadiazole units were synthesized and their structures were well-established using various spectroscopic techniques. 3-(1-(5-(3-(1H-indol-3-yl) propyl)-1,3,4-thiadiazol-2-ylimino)ethyl)-6-bromo-2H-chromen-2-one (IPTBC) exhibited dosedependent cytotoxicity in breast adenocarcinoma (MCF-7) cells. The circumvention of apoptosis is a prominent hallmark of cancer and hence triggering apoptosis in specific cancer cells is one of the convenient and widely used approaches for the development of anticancer chemotherapeutics. The induction of apoptosis upon treatment with IPTBC was confirmed by multiple apoptosis assays like Acridine orange-ethidium bromide, Hoechst staining, TUNEL staining, and colorimetric quantification using APOPercentage™ Apoptosis assay. The apoptosis initialisation through the active involvement of caspases was confirmed by caspase profiling tests. The wound healing assay displayed an intense impairment in the motility of MCF-7 cells suggesting the anti-metastatic potential of IPTBC. The ability of IPTBC to inhibit the antiapoptotic Bcl-2 protein by acting as a small molecule BH3 mimetic was explored through docking simulation studies. Although auxiliary investigations are warranted with this promising thiadiazole hybrid IPTBC, the perspective anticancer potential through programmed cell death, antimetastatic and probable Bcl-2 inhibitory action will enable its further exploration in oncology.

Item Type: Article
Uncontrolled Keywords: Apoptosis, Bcl-2, Cell cycle, Cytotoxicity, IPTBC, Metastasis
Subjects: Engineering > MIT Manipal > Chemistry
Depositing User: MIT Library
Date Deposited: 16 Jun 2017 10:20
Last Modified: 16 Jun 2017 10:20
URI: http://eprints.manipal.edu/id/eprint/149068

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