Design, synthesis, and molecular docking study of novel cinnoline derivatives as potential inhibitors of tubulin polymerization
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Eman Mohammad Mahmoud
and
Raid Abdel-Jalil
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.
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Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.
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Research funding: None declared.
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Conflict of interest statement: The authors declare that they have no conflict of interest regarding this article.
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Articles in the same Issue
- Frontmatter
- Editorial
- Organic chemistry and medicinal applications
- Research Articles
- Nitroimidazoles Part 10. Synthesis, crystal structure, molecular docking, and anticancer evaluation of 4-nitroimidazole derivatives combined with piperazine moiety
- Antibacterial, antioxidant, and cytotoxic activities of Syzygium aromaticum (L.) Merr. & Perry essential oil with identification of its chemical constituents
- Design, synthesis and antimicrobial assessments of aminoacetylenic-piperazine nitroimidazole hybrid compounds
- Design, synthesis, and molecular docking study of novel cinnoline derivatives as potential inhibitors of tubulin polymerization
- Thiophene ring-opening reactions VI. Attempted cyclization towards [fused]-tricyclic system involving a thiolate anion and suitably located electrophilic carbon
- Thermodynamic control synthesis of spiro[oxindole-3,3′-pyrrolines] via 1,4-dipolar cycloaddition utilizing imidazo[1,5-a]quinoline
- Bioactive secondary metabolites from Trichoderma viride MM21: structure elucidation, molecular docking and biological activity
- 8-Amino-7-(aryl/hetaryl)fluoroquinolones. An emerging set of synthetic antibacterial agents
Articles in the same Issue
- Frontmatter
- Editorial
- Organic chemistry and medicinal applications
- Research Articles
- Nitroimidazoles Part 10. Synthesis, crystal structure, molecular docking, and anticancer evaluation of 4-nitroimidazole derivatives combined with piperazine moiety
- Antibacterial, antioxidant, and cytotoxic activities of Syzygium aromaticum (L.) Merr. & Perry essential oil with identification of its chemical constituents
- Design, synthesis and antimicrobial assessments of aminoacetylenic-piperazine nitroimidazole hybrid compounds
- Design, synthesis, and molecular docking study of novel cinnoline derivatives as potential inhibitors of tubulin polymerization
- Thiophene ring-opening reactions VI. Attempted cyclization towards [fused]-tricyclic system involving a thiolate anion and suitably located electrophilic carbon
- Thermodynamic control synthesis of spiro[oxindole-3,3′-pyrrolines] via 1,4-dipolar cycloaddition utilizing imidazo[1,5-a]quinoline
- Bioactive secondary metabolites from Trichoderma viride MM21: structure elucidation, molecular docking and biological activity
- 8-Amino-7-(aryl/hetaryl)fluoroquinolones. An emerging set of synthetic antibacterial agents
