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Synthesis and cytotoxic evaluation of combretastatin A-4 analogues of benzo[b]furans

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Abstract

A series of benzo[b]furans was synthesized with modification at the 5-position of the benzene ring by introducing different aryl acetylenyl and acrylic acid moiety as combretastatin A-4 analogues. The compounds were evaluated by MTT assay for cytotoxic effects against lung cancer (A549), liver cancer (BEL-7404), colon cancer (SW620), and cervical cancer (HeLa) cell lines and the compounds were more sensitive to A549 and Hela cell lines. One compound exhibited the highest inhibition against A549 and Hela cells (IC50 = 0.18 and 0.14 μM) and very close to that of CA-4 (IC50 = 0.16 and 0.12 μM). This compound elicited cell-cycle arrest in the G2/M phase and significantly induced apoptosis in HeLa cells. Molecular docking studies indicated that it displayed hydrogen-bonding interactions with the amino acid residues Gln-11 and Tyr-224 would be a potential tululin inhibitor.

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Acknowledgements

This research was funded by Scientific Research Program of the Higher Education Institution of Xin Jiang (FSRPHEXJ Project No. XJEDU2016I031) and Xinjiang Medical University (Project No. CXCY097). We thank them for the financial support given to the research projects.

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Authors and Affiliations

  1. Department of Medicinal and Organic Chemistry, School of Pharmacy, Xinjiang Medical University, Urumqi, 830011, China

    Ye Fan, Yang Luo & Cheng Ma

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  1. Ye Fan
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  2. Yang Luo
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  3. Cheng Ma
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Correspondence to Cheng Ma.

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Fan, Y., Luo, Y. & Ma, C. Synthesis and cytotoxic evaluation of combretastatin A-4 analogues of benzo[b]furans. Monatsh Chem 148, 1823–1832 (2017). https://doi.org/10.1007/s00706-017-2001-1

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  • DOI: https://doi.org/10.1007/s00706-017-2001-1

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