Design, synthesis, and molecular docking study of novel cinnoline derivatives as potential inhibitors of tubulin polymerization.

Autor:	Mahmoud EM; Faculty of Zarka College, Al-Balqa' Applied University, Zarka, Jordan., Shongwe M; Department of Chemistry, College of Science, Sultan Qaboos University, P.O. Box 36, P.C. 123, Muscat, Sultanate of Oman., Moghadam ES; Department of Chemistry, College of Science, Sultan Qaboos University, P.O. Box 36, P.C. 123, Muscat, Sultanate of Oman.; Department of Medicinal Chemistry, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, 1417614411, Iran., Moghimi-Rad P; Department of Medicinal Chemistry, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, 1417614411, Iran., Stoll R; Biomolecular NMR, Ruhr University of Bochum, D-44780, Bochum, Germany., Abdel-Jalil R; Department of Chemistry, College of Science, Sultan Qaboos University, P.O. Box 36, P.C. 123, Muscat, Sultanate of Oman.
Jazyk:	angličtina
Zdroj:	Zeitschrift fur Naturforschung. C, Journal of biosciences [Z Naturforsch C J Biosci] 2022 Aug 23; Vol. 78 (3-4), pp. 123-131. Date of Electronic Publication: 2022 Aug 23 (Print Publication: 2023).
DOI:	10.1515/znc-2022-0087
Abstrakt:	The preparation of a novel 4-methylbenzo[ h ] cinnolines entity via a three-step synthetic protocol is described. Cyclization of the naphthylamidrazones, in the presence of polyphosphoric acid (PPA), furnishes the respective target benzo[ h ]cinnolines directly. This one-pot synthesis involves intramolecular Friedel-Crafts acylation followed by instant elimination under heating conditions. It is noteworthy that the yield of the product from this step decreases dramatically if the heating is extended beyond 3 h. The target novel cinnolone derivatives were identified by mass spectrometry and their structures elucidated by spectroscopic techniques. Subsequently, molecular docking was performed to shed light on the putative binding mode of the newly synthesized cinnolines. The docking results indicate that these derivatives are potential inhibitors of tubulin polymerization and the best interaction was achieved with a computational ki = 0.5 nM and posed correctly over the lexibulin. (© 2022 Walter de Gruyter GmbH, Berlin/Boston.)
Databáze:	MEDLINE
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