Carbohydrazones as new class of carbonic anhydrase inhibitors: Synthesis, kinetics, and ligand docking studies

• Published in: Bioorganic chemistry Vol. 72; pp. 89 - 101
• Main Authors: Iqbal, Sarosh, Saleem, Muhammad, Azim, M. Kamran, Taha, Muhammad, Salar, Uzma, Khan, Khalid Mohammed, Perveen, Shahnaz, Choudhary, M. Iqbal
• Format: Journal Article
• Language: English
• Published: SAN DIEGO Elsevier Inc 01.06.2017; Elsevier
• Subjects: Animals; Biochemistry & Molecular Biology; bis-Schiff bases; Carbohydrazones; Carbonic anhydrase II inhibitors; Carbonic Anhydrase Inhibitors - chemical synthesis; Carbonic Anhydrase Inhibitors - chemistry; Carbonic Anhydrase Inhibitors - pharmacology; Carbonic Anhydrases - metabolism; Cattle; Cheminformatic analysis; Chemistry; Chemistry, Organic; Dose-Response Relationship, Drug; Hydrazones - chemical synthesis; Hydrazones - chemistry; Hydrazones - pharmacology; Kinetic studies; Kinetics; Life Sciences & Biomedicine; Ligand docking; Ligands; Molecular Docking Simulation; Molecular Structure; Physical Sciences; Science & Technology; Structure-Activity Relationship; Cheminformatic analysis; Ligand docking; Carbohydrazones; bis-Schiff bases; Carbonic anhydrase II inhibitors; Kinetic studies; TRANSITION-METAL-COMPLEXES; COPPER(II); CRYSTAL; NICKEL(II); ZINC(II) COMPLEXES; THERAPEUTIC APPLICATIONS; SCHIFF-BASES; AGENTS; ANION SCAVENGERS; PENTAGONAL BIPYRAMIDAL COMPLEXES
• ISSN: 0045-2068; 1090-2120
• DOI: 10.1016/j.bioorg.2017.03.014

[Display omitted] •Carbohydrazones 1–27 were synthesized and evaluated for in vitro carbonic anhydrase inhibitory potential.•Many compounds were found to be potent analogs.•Cheminformatic analysis was performed.•In addition, kinetic and molecular docking studies were also performed. Discovery and development of carbonic anhydrase inhibitors is crucial for their clinical use as antiepileptic, diurectic and antiglaucoma agents. Keeping this in mind, we have synthesized carbohydrazones 1–27 and evaluated them for their in vitro carbonic anhydrase inhibitory potential. Out of twenty-seven compounds, compounds 1 (IC50=1.33±0.01µM), 2 (IC50=1.85±0.24µM), 3 (IC50=1.37±0.06µM), and 9 (IC50=1.46±0.12µM) have showed carbonic anhydrase inhibition better than the standard drug zonisamide (IC50=1.86±0.03µM). Moreover, compounds 4 (IC50=2.32±0.04µM), 5 (IC50=3.96±0.35µM), 7 (IC50=2.33±0.02µM), and 8 (IC50=2.67±0.01µM) showed good inhibitory activity. Cheminformatic analysis has shown that compounds 1 and 2 possess lead-like properties. In addition, kinetic and molecular docking studies were also performed to investigate the binding interaction between carbohydrazones and carbonic anhydrase enzyme. This study has identified a novel and potent class of carbonic anhydrase inhibitors with the potential to be investigated further.