Synthesis, Bioactivity Assessment, and Molecular Docking of Non-sulfonamide Benzimidazole-Derived N-Acylhydrazone Scaffolds as Carbonic Anhydrase-II Inhibitors

Abstract

This research reports the synthesis of new benzimidazole-derived N -acylhydrazones (NAH), their characterization using various spectroscopic methods, and in vitro evaluation as potent carbonic anhydrase-II inhibitors. Among the target compounds ( 9–29 ), few showed higher inhibition than the standard acetazolamide (IC 50 : 18.6 ± 0.43 μM), for example, compound 9 (IC 50 : 13.3 ± 1.25 μM), 10 (IC 50 : 17.2 ± 1.24 μM), 12 (IC 50 : 14.6 ± 0.62 μM), and 15 (IC 50 : 14.5 ± 1.05 μM). Molecular docking was performed on the most active compounds, which revealed their binding interactions with the active site of the enzyme, thus supporting the experimental findings.

Potential Health Benefits of Banana Phenolic Content during Ripening by Implementing Analytical and In Silico Techniques

“…This simple transformation is involved in a wide range of physiological processes (such as pH regulation, gas exchange, ion transport, bone resorption, fatty acid metabolism, etc.) [ 48 ]. In addition, CAs are associated with a plethora of pathological conditions, including glaucoma, edema, epilepsy, obesity, hypertension, cancer, neuropathic pain, and other neurological disorders [ 49 , 50 ].…”

Design, synthesis, and evaluation of novel bistrifluoromethyl‐based hydrazones as dual inhibitors of acetylcholinesterase and carbonic anhydrase enzymes for Alzheimer's disease

“…In this study, the new nonclassical CA inhibitors were focused on designs that did not contain either sulfamide or sulfonamide. It was mentioned previously that the conventional CA inhibitors are nonselective, that is why they can cause unexpected different inhibitors and side effects; moreover, a massive part of the population worldwide has an allergy to sulfamides or sulfonamides (Saadiq et al., 2021). Upon thorough examination of the interaction between sulfonamide/sulfanamide derivatives and CAs, it becomes apparent that a sulfamide or sulfonamide group is involved in coordinating the zinc cation within the catalytic domain of hCA.…”

Novel 5-(Arylideneamino)-1H-Benzo[d]imidazole-2-thiols as Potent Anti-Diabetic Agents: Synthesis, In Vitro α-Glucosidase Inhibition, and Molecular Docking Studies

“…The target compounds 7a–m were finally synthesized by refluxing the equimolar amounts of 5 with different aromatic aldehydes 6a–m for 4–6 h catalyzed using 3–5 drops of organic or mineral acids. 11 After completion, the product was precipitated in freezing water, filtered, washed, and dried. All the compounds were colored solids, having high melting points and soluble in polar solvents.…”

“…Our research group has previously reported benzimidazole-based antioxidants (IC 50 : 131.50 ± 12.39; IC 50 : 167.4 ± 7.4), α-glucosidase (IC 50 : 352 μg/mL), cholinesterase (IC 50 : 121.2 μM and 38.3 μM), and carbonic anhydrase inhibitors (IC 50 : 13.3 ± 1.25 μM). 10 , 11 …”