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

Muhammad Saadiq; Ghias Uddin; Abdul Latif; Mumtaz Ali; Nazia Akbar; Ammara; Sardar Ali; Manzoor Ahmad; Mohammad Zahoor; Ajmal Khan; Ahmed Al-Harrasi

doi:10.1021/acsomega.1c05362

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

ACS Omega. 2021 Dec 20;7(1):705-715. doi: 10.1021/acsomega.1c05362. eCollection 2022 Jan 11.

Authors

Affiliations

¹ Institute of Chemical Sciences, University of Peshawar, Peshawar, Khyber Pakhtunkhwa 25120, Pakistan.
² Department of Chemistry, University of Malakand, Dir (Lower), Chakdara, Khyber Pakhtunkhwa 18800, Pakistan.
³ Department of Biotechnology & Genetic Engineering, Hazara University, Mansehra, Khyber Pakhtunkhwa, 21120, Pakistan.
⁴ Department of Biochemistry, University of Malakand, Dir (Lower), Chakdara, Khyber Pakhtunkhwa 18800, Pakistan.
⁵ UoN Chair of Oman's Medicinal Plants and Marine Natural Products, University of Nizwa, Nizwa 616, Sultanate of Oman.

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 (IC₅₀: 18.6 ± 0.43 μM), for example, compound 9 (IC₅₀: 13.3 ± 1.25 μM), 10 (IC₅₀: 17.2 ± 1.24 μM), 12 (IC₅₀: 14.6 ± 0.62 μM), and 15 (IC₅₀: 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.