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

Autor: Ahmed EY; Chemistry of Natural Compounds Department, National Research Centre, Pharmaceutical and Drug Industries Research Institute, Cairo, Egypt., Abdelhafez OM; Chemistry of Natural Compounds Department, National Research Centre, Pharmaceutical and Drug Industries Research Institute, Cairo, Egypt., Zaafar D; Pharmacology and Toxicology Department, Faculty of Pharmacy, Modern University for Technology and Information, Cairo, Egypt., Serry AM; Pharmaceutical Chemistry Department, Faculty of Pharmacy, Modern University for Technology and Information, Cairo, Egypt., Ahmed YH; Cytology and Histology Department, Faculty of Veterinary Medicine, Cairo University, Cairo, Egypt., El-Telbany RFA; Biochemistry Department, Faculty of Pharmacy, Modern University for Technology and Information, Cairo, Egypt., Abd Elmageed ZY; Department of Pharmacology, Edward Via College of Osteopathic Medicine, University of Louisiana, Monroe, Michigan, USA., Ali HI; Department of Pharmaceutical Sciences, Irma Lerma Rangel College of Pharmacy, Texas A&M University, College Station, Texas, United States.
Jazyk: angličtina
Zdroj: Archiv der Pharmazie [Arch Pharm (Weinheim)] 2022 Jun; Vol. 355 (6), pp. e2100327. Date of Electronic Publication: 2022 Mar 14.
DOI: 10.1002/ardp.202100327
Abstrakt: 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 (IC 50 : 0.07-2.94 μM) against the MCF-7 cell line, compared with lapatinib (IC 50 : 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.
(© 2022 Deutsche Pharmazeutische Gesellschaft.)
Databáze: MEDLINE
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