Synthesis and biological evaluation of 3-functionalized 2-phenyl- and 2-alkylbenzo[b]furans as antiproliferative agents against human melanoma cell line |
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| Affiliation: | 1. Department of Chemistry, The Chinese University of Hong Kong, Shatin, China;4. Shenzhen Municipal Key Laboratory of Chemical Synthesis of Medicinal Organic Molecules & Shenzhen Center of Novel Functional Molecules, Shenzhen Research Institute, The Chinese University of Hong Kong, Shenzhen, China;5. Department of Chemistry & State Key Laboratory of Synthetic Chemistry, The Chinese University of Hong Kong, Shatin, China |
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| Abstract: | 
The key function of microtubules and mitotic spindle in cell division make them attractive targets in anticancer therapy. In the present study, functionalized in 3 position 2-phenyl- and 2-alkylbenzo[b]furans were synthesized and evaluated as antitumor agents. Among the synthesized derivatives 13a, 13b and 14 exhibited the most potent antiproliferative activity against human melanoma A375 cell line with IC50 values of 2.85 µM, 0.86 µM, 0.09 µM, respectively. The most promising compound defined was 14 with three methoxy groups in the 3-aroyl substituent and 7-methoxy group in 2-phenylbenzo[b]furan skeleton. Tubulin polymerization assay, confocal microscopy imaging and flow cytometry analysis revealed that 2-phenyl-3-aroylbenzo[b]furans (13a, 13b and 14) inhibited tubulin polymerization leading to disruption of mitotic spindle formation, cell cycle arrest in G2/M phase and apoptosis. |
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| Keywords: | Acylation Anti-tubulin agents Antitumor agents Melanoma A375 cell line |
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