Issue 9, 2017

Click chemistry-assisted synthesis of triazolo linked podophyllotoxin conjugates as tubulin polymerization inhibitors

Abstract

A series of new triazolo linked 4β-amidopodophyllotoxin conjugates (9a–l) were synthesized using click chemistry and evaluated for their antitumor activity against four human cancer cell lines. Among them, two compounds (9c and 9j) showed significant anticancer activity with IC50 values of 0.9 and 0.07 μM, respectively. Biological studies are conducted into the cell-cycle distribution of these conjugates inducing G2/M-phase arrest, apart from an increase in the levels of caspase-3 proteins, followed by apoptotic cell death. A tubulin polymerization assay analysis showed that these compounds effectively inhibit microtubule assembly in HeLa cells and, moreover, Hoechst 33258 and Immunohistochemistry staining suggest that these compounds induce cell death by apoptosis. The docking studies showed that compounds 9c and 9j interact and bind efficiently with the tubulin protein at the colchicine site.

Graphical abstract: Click chemistry-assisted synthesis of triazolo linked podophyllotoxin conjugates as tubulin polymerization inhibitors

Supplementary files

Article information

Article type
Research Article
Submitted
27 May 2017
Accepted
14 Jul 2017
First published
18 Jul 2017

Med. Chem. Commun., 2017,8, 1817-1823

Click chemistry-assisted synthesis of triazolo linked podophyllotoxin conjugates as tubulin polymerization inhibitors

M. V. P. S. Vishnuvardhan, S. R. V., K. Chandrasekhar, V. Lakshma Nayak, I. B. Sayeed, A. Alarifi and A. Kamal, Med. Chem. Commun., 2017, 8, 1817 DOI: 10.1039/C7MD00273D

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