Design, synthesis, cytotoxic activities, and molecular docking of chalcone hybrids bearing 8-hydroxyquinoline moiety with dual tubulin/EGFR kinase inhibition.

Autor: Amin MM; Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Al-Azhar University, Assiut 71524, Egypt., Abuo-Rahma GEA; Department of Medicinal Chemistry, Faculty of Pharmacy, Minia University, Minia 61519, Egypt; Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Deraya University, Minia 61519, Egypt. Electronic address: gamal.aborahama@mu.edu.eg., Shaykoon MSA; Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Al-Azhar University, Assiut 71524, Egypt., Marzouk AA; Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Al-Azhar University, Assiut 71524, Egypt; National Center for Natural Products Research, School of Pharmacy, University of Mississippi, MS 38677, USA., Abourehab MAS; Department of Pharmaceutics, Faculty of Pharmacy, Umm Al-Qura University, Makkah 21955, Saudi Arabia., Saraya RE; Department of Pharmaceutical Analytical Chemistry, Faculty of Pharmacy, Port Said University, Port Said 42515, Egypt., Badr M; Department of Biochemistry, Faculty of Pharmacy, Menoufia University, Menoufia, Egypt., Sayed AM; Department of Pharmacognosy, Faculty of Pharmacy, Nahda University, 62513 Beni-Suef, Egypt., Beshr EAM; Department of Medicinal Chemistry, Faculty of Pharmacy, Minia University, Minia 61519, Egypt. Electronic address: eman_beshr@mu.edu.eg.
Jazyk: angličtina
Zdroj: Bioorganic chemistry [Bioorg Chem] 2023 May; Vol. 134, pp. 106444. Date of Electronic Publication: 2023 Feb 25.
DOI: 10.1016/j.bioorg.2023.106444
Abstrakt: The present study established thirteen novel 8-hydroxyquinoline/chalcone hybrids3a-mof hopeful anticancer activity. According to NCI screening and MTT assay results, compounds3d-3f, 3i,3k,and3ldisplayed potent growth inhibition on HCT116 and MCF7 cells compared to Staurosporine. Among these compounds,3eand3fshowed outstanding superior activity against HCT116 and MCF7 cells and better safety toward normal WI-38 cells than Staurosporine. The enzymatic assay revealed that3e,3d, and3ihad goodtubulin polymerization inhibition (IC 50  = 5.3, 8.6, and 8.05 µM, respectively) compared to the reference Combretastatin A4 (IC 50  = 2.15 µM). Moreover,3e,3l, and3fexhibited EGFR inhibition (IC 50  = 0.097, 0.154, and 0.334 µM, respectively) compared to Erlotinib (IC 50  = 0.056 µM). Compounds3eand3fwere investigated for their effects on the cell cycle, apoptosis induction, andwnt1/β-cateningene suppression. The apoptosis markers Bax, Bcl2, Casp3, Casp9, PARP1, and β-actin were detected by Western blot. In-silico molecular docking, physicochemical, and pharmacokinetic studies were implemented for the validation of dual mechanisms and other bioavailability standards. Hence, Compounds3eand3fare promising antiproliferative leads with tubulin polymerization and EGFR kinase inhibition.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2023 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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