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ID: ALA4270617

Journal: Eur J Med Chem

Title: Design, synthesis, antimicrobial, antiquorum-sensing and antitumor evaluation of new series of pyrazolopyridine derivatives.

Authors: El-Gohary NS, Shaaban MI.

Abstract: New series of pyrazolopyridines 1-15 were synthesized and esteemed for antimicrobial effectiveness against S. aureus, B. cereus, E. coli, P. aeruginosa, C. albicans, A. fumigatus and A. flavus. Analogs 15c and 15d have eminent and broad spectrum antimicrobial activity, while 13a, 15a, 15e and 15f have potent effectiveness on S. aureus and B. cereus. In addition, 12 exhibited excellent effectiveness on E. coli and P. aeruginosa. Compounds 1-15 were also evaluated for antiquorum-sensing efficacy over C. violacium, whereas 11a, 15b, 15e and 15f showed reasonable efficacy. In vitro antitumor testing of the new analogs against HepG2, MCF-7 and Hela cancer cell lines revealed that 1 and 15d have potent and broad spectrum antitumor activity. In addition, 4, 8 and 15f showed prominent effectiveness on the three chosen cancer cell lines. In vivo antitumor assessment toward EAC in mice revealed that compounds 1 and 15d have the highest efficacy. Furthermore, cytotoxicity evaluation against W138 and WISH normal cells indicated that all screened compounds have lower cytotoxicity than doxorubicin over both normal cell lines. The active antimicrobial and antitumor compounds were estimated for DNA-binding affinity. Compounds 1, 15c and 15d exhibited strong affinity, and they were subsequently docked into DNA, where they displayed good interactions with DNA. In silico studies indicated that the new compounds are predicted to exhibit good oral absorption.

CiteXplore: 30138804

DOI: 10.1016/j.ejmech.2018.08.008