Exploring sulfamoylureas as multi-target agents: Inhibition of hCA I/II and cholinesterases
Journal of Molecular Structure, cilt.1376, 2026 (SCI-Expanded, Scopus)
- Yayın Türü: Makale / Tam Makale
- Cilt numarası: 1376
- Basım Tarihi: 2026
- Doi Numarası: 10.1016/j.molstruc.2026.146974
- Dergi Adı: Journal of Molecular Structure
- Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Chemical Abstracts Core, Chimica, Compendex, INSPEC, Academic Search Ultimate (EBSCO), Engineering Source (EBSCO)
- Anahtar Kelimeler: ADME Studies, Biological activity, MD Simulation, Molecular docking, Sulfamoylureas
- Atatürk Üniversitesi Adresli: Evet
Özet
Sulfonylureas and their bioisosteric analogs, sulfamoylureas, are known for their significant pharmacological activities. In this study, a novel series of sulfamoylurea derivatives was synthesized via a one-pot reaction of amines with chlorosulfonyl isocyanate (CSI), yielding satisfactory results. The inhibitory activities of these compounds were evaluated against key human enzymes, including acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and carbonic anhydrase isoforms I and II (hCA I and hCA II).The synthesized derivatives exhibited moderate, and selective inhibition. IC50 values ranged from 12.24 ± 0.31 to 177.7 ± 11.64 µM for AChE, and 1.38 ± 0.04 to 152.61 ± 8.43 µM for BChE. For hCA I and II, IC50 values were 10.51 ± 0.078–324.66 ± 5.01 µM and 12.57 ± 0.137–193.72 ± 1.48 µM, respectively. Selectivity studies revealed that (R, R)-21 and (R, R)-20 inhibited AChE 11.64- and 6.13-fold more effectively than BChE, whereas 17 and 15 showed 9.29- and 8.87-fold preference for BChE. Compounds (S, S)-20 and 15 were 11.68- and 11.18-fold more selective for hCA I, while 14 and 17 showed 13.09- and 25.82-fold selectivity toward hCA II.In general, the results demonstrate that sulfamoylurea derivatives exhibit inhibitory activity against both cholinesterases and carbonic anhydrases. These findings suggest that these compounds could be considered multi-target inhibitors; however, further studies are needed to confirm their therapeutic potential.