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  3. Design, synthesis, biological evaluation and docking analysis of pyrrolidine-benzenesulfonamides as carbonic anhydrase or acetylcholinesterase inhibitors and antimicrobial agents

Design, synthesis, biological evaluation and docking analysis of pyrrolidine-benzenesulfonamides as carbonic anhydrase or acetylcholinesterase inhibitors and antimicrobial agents

  • J Biomol Struct Dyn. 2024 Apr;42(7):3441-3458. doi: 10.1080/07391102.2023.2214224.
Samet Poyraz 1,  H Ali Döndaş 1 2,  Cem Yamali 1,  Samet Belveren 1,  Yeliz Demir 3,  Sabriye Aydınoglu 4,  Naciye Yaktubay Döndaş 5,  Tugba Taskin-Tok 6 7,  Senanur Taş 2,  Mahmut Ülger 8,  Jose M Sansano 9
Affiliations

Affiliations

  • 1 Department of Basic Pharmaceutical Sciences, Faculty of Pharmacy, Çukurova University, Balcalı, Adana, Türkiye.
  • 2 Department of Biotechnology, Institute of Natural and Applied Sciences, Çukurova University, Balcalı, Adana, Türkiye.
  • 3 Department of Pharmacy Services, Nihat Delibalta Göle Vocational High School, Ardahan University, Ardahan, Türkiye.
  • 4 Department of Analytical Chemistry, Faculty of Pharmacy, Çukurova University, Balcalı, Adana, Türkiye.
  • 5 Department of Pharmacology, Faculty of Medicine, Çukurova University, Balcalı, Adana, Türkiye.
  • 6 Department of Chemistry, Faculty of Arts and Sciences, Gaziantep University, Gaziantep, Türkiye.
  • 7 gDepartment of Bioinformatics and Computational Biology, Institute of Health Sciences, Gaziantep University, Gaziantep, Türkiye.
  • 8 Department of Pharmaceutical Microbiology, Faculty of Pharmacy, Mersin University, Mersin, Türkiye.
  • 9 Department of Organic Chemistry, Centro de Innovación en Química Avanzada (ORFEO-CINQA), University of Alicante, and Instituto de Síntesis Orgánica (ISO), Alicante, Spain.
PMID: 37232497 DOI: 10.1080/07391102.2023.2214224
Abstract

The synthesis and biological assessment of novel multi-functionalized pyrrolidine-containing benzenesulfonamides were reported along with their antimicrobial, Antifungal, CAs inhibition, and AChE inhibition as well as DNA-binding effects. The chemical structure of the compounds was elucidated by using FTIR, NMR, and HRMS. Compound 3b, which had Ki values of 17.61 ± 3.58 nM (hCA I) and 5.14 ± 0.61 nM (hCA II), was found the be the most potent CAs inhibitor. Compounds 6a and 6b showed remarkable AChE inhibition effects with Ki values 22.34 ± 4.53 nM and 27.21 ± 3.96 nM in comparison to tacrine. Compounds 6a-6c had moderate antituberculosis effect on M. tuberculosis with a MIC value of 15.62 μg/ml. Compounds had weaker Antifungal and Antibacterial activity in the range of MIC 500-62.5 μg/ml against standard Bacterial and Fungal strains. Besides these above, molecular docking studies were performed to examine and evaluate the interaction of the remarkable compounds (3b, 6a and 6b) against the current Enzymes (CAs and AChE). Novel compounds gained interest in terms of Enzyme inhibitory potencies. Therefore, the most potent Enzyme inhibitors may be considered lead compounds to be modified for further research.Communicated by Ramaswamy H. Sarma.

Keywords

Acetylcholinesterase; antimicrobial; benzenesulfonamide; carbonic anhydrase; molecular docking; pyrazole; pyrrolidines.

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