2. Academic Validation
  3. Facile synthesis of aminobiphenyl sulfonamides via Chan-Lam coupling and their biological evaluation as potent carbonic anhydrase inhibitors

Facile synthesis of aminobiphenyl sulfonamides via Chan-Lam coupling and their biological evaluation as potent carbonic anhydrase inhibitors

  • Sci Rep. 2025 Jul 15;15(1):25661. doi: 10.1038/s41598-025-10048-4.
Moniba Sharif 1,  Abid Mahmood 2,  Aqsa Kanwal 1,  Matloob Ahmad 1,  Nasir Rasool 3,  Muhammad Usman Qamar 4,  Mohammed H Al Mughram 5,  Amira Ali Mohammed Al-Harethi 6,  Tawaf Ali Shah 7,  Imran Ibrahim Shaikh 8
Affiliations

Affiliations

  • 1 Department of Chemistry, Government College University Faisalabad, Faisalabad, 38000, Pakistan.
  • 2 Department of Pharmaceutical Chemistry, Government College University Faisalabad, Faisalabad, 38000, Pakistan.
  • 3 Department of Chemistry, Government College University Faisalabad, Faisalabad, 38000, Pakistan. nasirrasool@gcuf.edu.pk.
  • 4 institute of Microbiology, Faculty of Life Sciences, Government College University, Faisalabad, 38000, Pakistan.
  • 5 Department of Pharmaceutical Chemistry, College of Pharmacy, King Khalid University, Abha, Saudi Arabia.
  • 6 Biological Science Department, Faculty of Science, Sana'a University, Sana'a, P.O 1111, Yemen. amira.alharethi90@gmail.com.
  • 7 College of Agriculture Engineering and Food Science, Shandong University of Technology, Zibo, 255000, China.
  • 8 Department of pharmacy, Central Laboratory of The Lishui Hospital of Wenzhou Medical University, The First Affiliated Hospital of Lishui University, Lishui People's, Hospital, Lishui, 323000, Zhejiang, China. drorthospine@outlook.com.
PMID: 40665010 DOI: 10.1038/s41598-025-10048-4
Abstract

Inhibition of carbonic anhydrases (EC 4.2.1.1, hCAs) is known to be a potential target for treatment of several disorders like epilepsy, glaucoma, obesity, and Cancer. The current research focuses on the synthesis of a series of 4'-amino-[1,1'-biphenyl]-4-sulfonamide derivatives (9a-e) through cross-coupling reactions in the presence of Cu(OAc)2 catalyst. The structural elucidation of synthesized derivatives was carried out through1H NMR, and13C NMR. These sulphonamide derivatives were screened for inhibitory potential towards various isozymes of carbonic anhydrases including hCA-II, hCA-IX, and hCA-XII. Enzyme inhibition assay exhibited that synthesized derivatives with IC50 ± SEM, 9e (0.38 ± 0.03µM), 9d (0.21 ± 0.03 µM) and 9b (0.69 ± 0.15 µM) had remarkable inhibition potency against hCA-II, hCA-IX and hCA-XII respectively. It was noted that 9d exhibited 8-fold more inhibitor potential as compared to standard inhibitor acetazolamide. For the most potent inhibitors, enzyme kinetic analysis was also carried out to find inhibition mode. Furthermore, the drug-ability of synthesized compounds was evaluated through SwissADME tools, and found that all the newly prepared derivatives successfully satisfied the drug-ability criteria. Molecular docking studies were conducted to identify the types of interactions between the synthesized ligands and the target proteins.

Keywords

In Silico studies; CA inhibitors; Chemical synthesis; Enzymes kinetics Inhibition; Sulfonamide derivatives.

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