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

Abstract 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 (IC 50  = 1.33 ± 0.01 µM), 2 (IC 50  = 1.85 ± 0.24 µM), 3 (IC 50  = 1.37 ± 0.06 µM), and 9 (IC 50  = 1.46 ± 0.12 µM) have showed carbonic anhydrase inhibition better than the standard drug zonisamide (IC 50  = 1.86 ± 0.03 µM ) . Moreover, compounds 4 (IC 50  = 2.32 ± 0.04 µM), 5 (IC 50  = 3.96 ± 0.35 µM), 7 (IC 50  = 2.33 ± 0.02 µM), and 8 (IC 50  = 2.67 ± 0.01 µM) 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.