Design, Synthesis, and Molecular Docking Study of Novel Cinnoline Derivatives As Potential Inhibitors of Tubulin Polymerization Publisher Pubmed



Mahmoud EM¹ ; Shongwe M² ; Moghadam ES^{2, 3} ; Moghimirad P³ ; Stoll R⁴ ; Abdeljalil R² Show Affiliations
Source: Zeitschrift fur Naturforschung - Section C Journal of Biosciences Published:2023

Abstract

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.