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Issue 2, 2010
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Novel 4β-anilino-podophyllotoxin derivatives: design synthesis and biological evaluation as potent DNA-topoisomerase II poisons and anti-MDR agents

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Abstract

A new series of 4β-anilino-podophyllotoxin analogs have been designed, synthesized and evaluated their bioactivities as novel DNA-topoisomerase II poisons as well as P-glycoprotein (P-gp)-dependent multidrug resistance (MDR) inhibitors. The new compounds show improved potency and efficacy with respect to the parent molecule etoposide (VP-16), one of the semisynthetic derivatives of podophyllotoxin. The treatment of 5kn in KB/VCR cells caused G2/M phase arrest and finally induced apoptosis. Furthermore, molecular docking is applied to testify that 5kn could not be the substrates of P-gp, which is consistent with the result of MDR1 and P-glycoprotein express tests. The most potent compound 5n is chosen for in vivo studies, the administration of 5n was effective in treatment of cancer with a lower dose than VP-16 in drug-sensitive xenograft model and drug-resistant xenograft model. Compound 5n is a potential drug candidate for anticancer chemotherapy.

Graphical abstract: Novel 4β-anilino-podophyllotoxin derivatives: design synthesis and biological evaluation as potent DNA-topoisomerase II poisons and anti-MDR agents

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Publication details

The article was received on 24 Jun 2009, accepted on 06 Oct 2009 and first published on 01 Dec 2009


Article type: Paper
DOI: 10.1039/B912336A
Mol. BioSyst., 2010,6, 410-420

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    Novel 4β-anilino-podophyllotoxin derivatives: design synthesis and biological evaluation as potent DNA-topoisomerase II poisons and anti-MDR agents

    C. Hu, D. Xu, W. Du, S. Qian, L. Wang, J. Lou, Q. He, B. Yang and Y. Hu, Mol. BioSyst., 2010, 6, 410
    DOI: 10.1039/B912336A

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