Synthesis of indole–quinoline–oxadiazoles: their anticancer potential and computational tubulin binding studies

Kamath, Pooja R and Sunil, Dhanya and Ajees, Abdul A (2016) Synthesis of indole–quinoline–oxadiazoles: their anticancer potential and computational tubulin binding studies. Research on Chemical Intermediates, 42 (6). pp. 5899-5914. ISSN 0922-6168

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Abstract

Small hybrid molecules with two or more structural pharmacores having different biological functions and distinct activity have gained a significant role in cancer drug development to combat various types of malignancies. The present study describes an efficient, clean and strategic synthesis of 12 new substituted quinoline–indole–oxadiazole hybrids from substituted 2-(quinolin-8-yloxy)acetohydrazides and indole-3-carboxylic acids by employing T3P� as a green catalyst. Structures of the newly synthesized compounds were established by IR, 1H NMR, 13C NMR, DEPT C-NMR and MS spectroscopic evidence, as well as CHN analysis data. All indole–quinoline–oxadiazoles were tested for their in vitro cytotoxic potential in breast adenocarcinoma (MCF7) and normal kidney (vero) cell lines using MTT assay. 8-((5-(3-(1H-indol-3-yl)propyl)-1,3,4-oxadiazol-2-yl)methoxy)quinoline (3d) exhibited a low IC50 value and a high selectivity index to MCF7 cells and also displayed a mitotic block in flow cytometric cell cycle progression analysis. Microtubule disruption can induce G2/M phase cell cycle arrest leading to abnormal mitotic spindle formation. Ligand 3d demonstrated its capability of being a probable tubulin inhibitor when docked in the colchicine domain of tubulin

Item Type: Article
Uncontrolled Keywords: Indole–quinoline–oxadiazole, � Cytotoxicity, � Mitosis, � Tubulin
Subjects: Engineering > MIT Manipal > Chemistry
Depositing User: MIT Library
Date Deposited: 02 Jun 2016 15:00
Last Modified: 02 Jun 2016 15:00
URI: http://eprints.manipal.edu/id/eprint/146275

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