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Issue 9, 2017
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Click chemistry-assisted synthesis of triazolo linked podophyllotoxin conjugates as tubulin polymerization inhibitors

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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

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Publication details

The article was received on 27 May 2017, accepted on 14 Jul 2017 and first published on 18 Jul 2017


Article type: Research Article
DOI: 10.1039/C7MD00273D
Citation: Med. Chem. Commun., 2017,8, 1817-1823
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    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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