Design, synthesis and anticancer evaluation of novel 1,3-benzodioxoles and 1,4-benzodioxines.

Autor: Hassan RM; Medicinal and Pharmaceutical Chemistry Department, Pharmaceutical and Drug Industries Research Division, National Research Centre (ID: 60014618), P.O. 12622, Dokki, Giza, Egypt., Abd-Allah WH; Pharmaceutical Chemistry Department, College of Pharmaceutical Science and Drug Manufacturing, Misr University for Science and Technology, P.O. 77, 6th of October City, Giza, Egypt., Salman AM; Medicinal and Pharmaceutical Chemistry Department, Pharmacology Group, Pharmaceutical and Drug Industries Research Division, National Research Centre (ID: 60014618), P.O. 12622, Dokki, Giza, Egypt., El-Azzouny AA; Medicinal and Pharmaceutical Chemistry Department, Pharmaceutical and Drug Industries Research Division, National Research Centre (ID: 60014618), P.O. 12622, Dokki, Giza, Egypt., Aboul-Enein MN; Medicinal and Pharmaceutical Chemistry Department, Pharmaceutical and Drug Industries Research Division, National Research Centre (ID: 60014618), P.O. 12622, Dokki, Giza, Egypt. Electronic address: mnaboulenein@yahoo.com.
Jazyk: angličtina
Zdroj: European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences [Eur J Pharm Sci] 2019 Nov 01; Vol. 139, pp. 105045. Date of Electronic Publication: 2019 Aug 14.
DOI: 10.1016/j.ejps.2019.105045
Abstrakt: A new set of 1,3-benzodioxoles and 1,4-benzodioxines was designed and synthesized starting from gallic acid as anticancer agents. The antiproliferative effect of the target compounds was evaluated against a panel of cancer cell lines (HepG2, PC-3, MCF-7 and A549) using MTT assay. The 1,4-benzodioxine derivative 11a manifested broad spectrum effect towards the four tested cancer cell lines (IC 50  < 10 μM) with lower toxic effect on normal human cell line BJ1. Cell cycle progression of MCF-7 after treatment with compound 11a was studied where it induced cells accumulation at G2/M phase as well as increasing in the percentage of cells at pre-G1. Compound 11a is found to be a tubulin polymerization inhibitor with IC 50  = 6.37 μM. Also, flow cytometeric analysis revealed that compound 11a could induce both early and late stage apoptosis in MCF-7 cell line. Moreover, the ability of this compound to stimulate apoptosis in the latter cell line was further confirmed by: increment of Bax/Bcl-2 ratio, increase the expression of tumor suppressor gene p53, boosting the levels of initiator and executioner caspases as well as raise in the amount of cytochrome C. In addition molecular docking study was accomplished on the colchicine binding site of tubulin (pdb: 1SA0) to illustrate the interactions of the most potent compound 11a to the receptor.
(Copyright © 2019 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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