Synthesis of benzimidazole-based hydrazones as potential anticarbonic anhydrase agents: a theoretical and experimental investigations

作者：Abdul Shakoor, Aftab Alam, Faheem Jan, Naeem Ullah, Mumtaz Ali, Mahboob Ali, Abid Ali, Abdullah F. Alasmari, Fawaz Alasmari, Ajmal Khan, Ahmed Al‐Harrasi, Momin Khan · 发表于：Zeitschrift für Naturforschung C · 年份：2025 · DOI：10.1515/znc-2025-0038 · 被引用次数：7 · 研究领域：Enzyme function and inhibition、Synthesis and Catalytic Reactions、Phenothiazines and Benzothiazines Synthesis and Activities

Abstract In this research, a series of new hydrazone-Schiff bases of benzimidazole were synthesized in good yields through three step reactions, and the structures were confirmed by means of modern spectroscopic techniques (HR-ESI-MS, 1 H-, and 13 C NMR). These compounds have been assessed for their in vitro carbonic anhydrase (CA) inhibitory activity, 12 derivatives showed potent inhibition (IC 50 = 13.29 ± 0.46 to 30.74 ± 1.28 µM) comparing to the acetazolamide as a standard (IC 50 = 18.20 ± 0.43 µM). Molecular docking studies exposed vital binding interactions and robust affinities with the CA active site. Electronic properties and structural stability were examined through DFT (B3LYP/6–311++G(d,p)), and intramolecular interactions were evaluated by means of DFT-D3 and reduced density gradient analysis. Furthermore, TD-DFT (CAM-B3LYP/6–311++G(d,p)) calculations provided insights into the electronic transitions and reactivity parameters like electron affinity, electronegativity, ionization energy, and chemical hardness, offering a deeper understanding of the compounds’ inhibitory mechanisms.