Synthesis, biological evaluation and molecular docking studies of novel amino acid-conjugated pyrazole-benzenesulfonamide hybrids against carbonic anhydrase I/II and acetylcholinesterase enzymes
Journal of Molecular Structure, vol.1376, 2026 (SCI-Expanded, Scopus)
- Publication Type: Article / Article
- Volume: 1376
- Publication Date: 2026
- Doi Number: 10.1016/j.molstruc.2026.146958
- Journal Name: Journal of Molecular Structure
- Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Chemical Abstracts Core, Chimica, Compendex, INSPEC, Academic Search Ultimate (EBSCO), Engineering Source (EBSCO)
- Keywords: Acetylcholinesterase, Carbonic anhydrase, Docking, Pyrazole, Sulfonamide
- Anadolu University Affiliated: Yes
Abstract
A series of novel amino acid-conjugated pyrazole-benzenesulfonamide derivatives (G1–7) was synthesized and evaluated against carbonic anhydrase I/II and acetylcholinesterase enzymes. Among the compounds, ethyl (1-(4-sulfamoylphenyl)-5-(thiophen-2-yl)-1H-pyrazole-3-carbonyl)tryptophanate (G3) emerged as the most potent hCA I (Ki: 28.63 ± 0.57 nM) and hCA II (Ki: 48.80 ± 13.00 nM). Methyl (1-(4-sulfamoylphenyl)-5-(thiophen-2-yl)-1H-pyrazole-3-carbonyl)tryptophanate (G5) demonstrated the highest inhibitory activity against AChE with Ki: 61.34 ± 8.88 nM. Molecular docking studies were also conducted, and binding scores were calculated for compounds G3 -7.784 kcal/mol (hCA I), -7.461 kcal/mol (hCA II), and G5 -9.102 kcal/mol (AChE). Experimental findings demonstrated that G3, an ethyl ester tryptophan derivative, is highly effective in inhibiting hCA I/II, while the methyl ester derivative G5 shows superior efficacy against AChE. Additionally, the phenylalanine-based hybrid G4 was found to be a more potent inhibitor of hCA II than hCA I. ADMET evaluations revealed that some hybrids possess favorable drug-like characteristics. These findings show that the potential of these compounds as promising structures for subsequent structural optimization and biological investigation.