Antitumor and multikinase inhibition activities of some synthesized coumarin and benzofuran derivatives

• Published in: Archiv der Pharmazie (Weinheim) 2022-06, Vol.355 (6), p.e2100327-n/a
• Main Authors: Ahmed, Eman Y., Abdelhafez, Omaima M., Zaafar, Dalia, Serry, Aya M., Ahmed, Yasmine H., El‐Telbany, Rania Farag A., Abd Elmageed, Zakaria Y., Ali, Hamed I.
• Format: Article
• Language: English
• Subjects: benzofuran; Breast cancer; Cell cycle; coumarin; Ehrlich tumor; kinases
• ISSN: 0365-6233; 1521-4184
• DOI: 10.1002/ardp.202100327

Two new series of coumarin and benzofuran derivatives were designed, synthesized, and assessed for their in vitro and in vivo antitumor activities against breast cancer. Compounds 8, 9, 14, 15, and 17 exhibited the best antiproliferative activities (IC50: 0.07−2.94 μM) against the MCF‐7 cell line, compared with lapatinib (IC50: 4.69 μM). Compound 14, with the most potent cytotoxic activity against MCF‐7 cells, was capable of enhancing preG1 apoptosis and triggering cell cycle arrest at the G2/M phase. The kinase inhibitory activity of compound 14 against a panel of 22 kinases was examined to reveal multikinase inhibition within −39% to −97%. Furthermore, compound 14 exhibited potent in vivo Ehrlich (mammary adenocarcinoma) tumor regression, positive caspase‐3, and negative EGFR immunoreaction, and was capable of elevating the catalase level. The physicochemical properties and pharmacokinetic parameters of compound 14 were investigated in silico for its druglikeness. Two new series of coumarin and benzofuran derivatives were designed, synthesized, and assessed for their in vitro and in vivo antitumor activities. Compounds 8, 9, 14, 15, and 17 exhibited the best antiproliferative activities compared with lapatinib. The most potent compound (14) was tested against a panel of 22 kinases, revealing multikinase inhibition between −39% and −97%. The physicochemical properties and pharmacokinetic parameters of compound 14 were investigated in silico for its druglikeness.