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  3. Synthesis, human carbonic anhydrase I and II inhibition, and in silico studies of 2-ethoxy-6-formylphenyl [1,1'-biphenyl]-4-sulfonate derived thiosemicarbazones

Synthesis, human carbonic anhydrase I and II inhibition, and in silico studies of 2-ethoxy-6-formylphenyl [1,1'-biphenyl]-4-sulfonate derived thiosemicarbazones

  • Bioorg Chem. 2025 Sep:164:108836. doi: 10.1016/j.bioorg.2025.108836.
Asad Rafiq 1,  Muhammad Tayyab 1,  Suraj N Mali 2,  Parham Taslimi 3,  Rahul D Jawarkar 4,  Shailesh S Gurav 5,  Xianliang Zhao 6,  Nastaran Sadeghian 3,  Furkan Çakır 7,  Zahid Shafiq 8,  Ahmed Mohamed Tawfeek 9,  Mohammad Shahidul Islam 10
Affiliations

Affiliations

  • 1 Institute of Chemical Sciences, Bahauddin Zakariya University, 60800, Multan, Pakistan.
  • 2 School of Pharmacy, D.Y. Patil University (Deemed to be University), Sector 7, Nerul, Navi Mumbai 400706, India.
  • 3 Department of Biotechnology, Faculty of Science, Bartin University, 74110 Bartin, Türkiye.
  • 4 Department of Pharmaceutical Chemistry, Dr Rajendra Gode Institute of Pharmacy, University mardi road, Ghatkheda, Amravati(444602), Maharashtra, India.
  • 5 Department of Chemistry, VIVA College, Virar (W), Maharashtra 401303, India.
  • 6 School of Biological and Chemical Engineering, Zhejiang University of Science and Technology, Hangzhou, Zhejiang Province, China.
  • 7 Bezmialem Vakif University, Faculty of Pharmacy, Department of Pharmaceutical Chemistry, 34093, Fatih, Istanbul, Türkiye.
  • 8 Institute of Chemical Sciences, Bahauddin Zakariya University, 60800, Multan, Pakistan. Electronic address: zahidshafiq@bzu.edu.pk.
  • 9 Department of Chemistry, College of Science, King Saud University, P. O. Box 2455, Riyadh 11451, Saudi Arabia.
  • 10 Department of Chemistry, College of Science, King Saud University, P. O. Box 2455, Riyadh 11451, Saudi Arabia. Electronic address: mislam@ksu.edu.sa.
PMID: 40768801 DOI: 10.1016/j.bioorg.2025.108836
Abstract

This study describes the synthesis and biological evaluation of 2-ethoxy-6-formylphenyl [1,1'-biphenyl]-4-sulfonate-based thiosemicarbazones 5(a-s) as potential inhibitors of human Carbonic Anhydrase isoforms hCA I and hCA II. Among the synthesized compounds, 5 k exhibited potent inhibition, with IC50 values of 89.25 nM and 54.50 nM for hCA I and hCA II, respectively, surpassing that of acetazolamide as the standard inhibitor. Structure-activity relationship (SAR) analysis indicates that the presence of electron withdrawing groups, especially the fluoro substituent, contributed to the enhanced inhibitory activity. Molecular docking and dynamics simulations demonstrated the strong binding capability of compound 5 k and showed its stability throughout the simulation period. Overall, these findings highlight 2-ethoxy-6-formylphenyl [1,1'-biphenyl]-4-sulfonate-based thiosemicarbazones, with 5 k notably, as promising candidates for the development of therapeutic agents targeting hCA I and hCA II.

Keywords

2-ethoxy-6-formylphenyl [1,1′-biphenyl]-4-sulfonate; Carbonic anhydrase inhibitors; Molecular docking; Thiosemicarbazone.

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