Synthesis and biological evaluation of 3-functionalized 2-phenyl- and 2-alkylbenzo[b]furans as antiproliferative agents against human melanoma cell line

• Published in: Bioorganic chemistry 2019-07, Vol.88, p.102930-102930, Article 102930
• Main Authors: Kwiecień, Halina, Perużyńska, Magdalena, Stachowicz, Karolina, Piotrowska, Katarzyna, Bujak, Joanna, Kopytko, Patrycja, Droździk, Marek
• Format: Article
• Language: English
• Subjects: Acylation; Anti-tubulin agents; Antitumor agents; Benzo[b]furans; Melanoma A375 cell line
• ISSN: 0045-2068; 1090-2120
• DOI: 10.1016/j.bioorg.2019.102930

[Display omitted] •An efficient synthesis of 2-phenylbenzo[b]furans is described.•Selective acylations of 2-phenyl- and 2-alkylbenzo[b]furans at 3-position are achieved.•3-Aroyl benzo[b]furans show antiproliferative activity against human melanoma A375 cell line.•Aroyl and methoxy groups contribute to anticancer activity of 2-phenylbenzo[b]furans.•The most active compounds (13a, 13b and 14) show IC50 values: 2.85 µM, 0.86 µM, 0.09 µM.•These compounds inhibit tubulin polymerization and disrupt mitotic spindle formation. 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.