Publication Date:
2019
Description:
〈p〉Publication date: Available online 1 July 2019〈/p〉
〈p〉〈b〉Source:〈/b〉 Bioorganic & Medicinal Chemistry Letters〈/p〉
〈p〉Author(s): Shu-Yi Hao, Shi-Liang Feng, Xing-Rong Wang, Zhichao Wang, Shi-Wu Chen, Ling Hui〈/p〉
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〈h5〉Abstract〈/h5〉
〈div〉〈p〉A series of conjugates of podophyllotoxin and coumarin were prepared using the click reaction, and their cytotoxicities against A549, HepG2, HeLa, and LoVo cells were evaluated. Among them, compound 〈strong〉14e〈/strong〉 exhibited the strongest cytotoxicities against these cancer cells with IC〈sub〉50〈/sub〉 values of 4.9–17.5 μM. Furthermore, 〈strong〉14e〈/strong〉 disrupted microtubules and induced cell cycle arrest at G1 phase by regulating P21 and Cyclin D1 in LoVo cells. In addition, 〈strong〉14e〈/strong〉 bond CT DNA and selectively inhibited Topo IIβ over Topo IIα. Molecular docking model showed that 〈strong〉14e〈/strong〉 appeared to form stable hydrogen bonds with several DNA bases and residue Gln778. Taken together, these conjugates have the potential to be developed as anti-tumor drugs.〈/p〉〈/div〉
〈/div〉
〈div xml:lang="en"〉
〈h5〉Graphical abstract〈/h5〉
〈div〉
〈p〉The conjugates of podophyllotoxin and coumarin disrupt the microtubules, induce cell cycle arrest in G1 phase, bind to CT DNA, and inhibit Topo-Ⅱβ in LoVo cells.〈/p〉
〈p〉〈figure〉〈img src="https://ars.els-cdn.com/content/image/1-s2.0-S0960894X19304457-ga1.jpg" width="429" alt="Graphical abstract for this article" title=""〉〈/figure〉〈/p〉
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〈/div〉
Print ISSN:
0960-894X
Electronic ISSN:
1464-3405
Topics:
Chemistry and Pharmacology
,
Medicine
