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Synthesis of 2-aryl-1,2,4-oxadiazolo-benzimidazoles: Tubulin polymerization inhibitors and apoptosis inducing agents

journal contribution
posted on 2024-11-02, 07:14 authored by Ahmed Kamal, Srinivasa Reddy TelukutlaSrinivasa Reddy Telukutla, M Vishnuvardhan, Vijaykumar Nimbarte, A. V. Subba Rao, Vunnam Srinivasulu, Nagula Shankaraiah
A new series of 2-aryl 1,2,4-oxadiazolo-benzimidazole conjugates have been synthesized and evaluated for their antiproliferative activity in the sixty cancer cell line panel of the National Cancer Institute (NCI). Compounds 5l (NSC: 761109/1) and 5x (NSC: 761814/1) exhibited remarkable cytotoxic activity against most of the cancer cell lines in the one dose assay and were further screened at five dose concentrations (0.01, 0.1, 1, 10 and 100 mu M) which showed GI(50) values in the range of 0.79-28.2 mu M. Flow cytometric data of these compounds showed increased cells in G2/M phase, which is suggestive of G2/M cell cycle arrest. Further, compounds 5l and 5x showed inhibition of tubulin polymerization and disruption of the formation of microtubules. These compounds induce apoptosis byDNAfragmentation and chromatin condensation as well as by mitochondrial membrane depolarization. In addition, structure activity relationship studies within the series are also discussed. Molecular docking studies of compounds 5l and 5x into the colchicine-binding site of the tubulin, revealed the possible mode of interaction by these compounds.

History

Journal

Bioorganic and Medicinal Chemistry

Volume

23

Issue

15

Start page

4608

End page

4623

Total pages

16

Publisher

Pergamon Press

Place published

United Kingdom

Language

English

Copyright

© 2015 Elsevier Ltd. All rights reserved.

Former Identifier

2006084324

Esploro creation date

2020-06-22

Fedora creation date

2018-10-04

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