Yaşar Ümit, Demir Yeliz, Gönül İlyas, Özaslan Muhammet Serhat, Çelik Gizem Gümüşgöz, Türkeş Cüneyt, Beydemir Şükrü
Department of Laboratory and Veterinary Health, Nihat Delibalta Göle Vocational High School, Ardahan University, Ardahan, Türkiye.
Department of Pharmacy Services, Nihat Delibalta Göle Vocational High School, Ardahan University, Ardahan, Türkiye.
Chem Biodivers. 2025 May;22(5):e202402893. doi: 10.1002/cbdv.202402893. Epub 2025 Jan 6.
Sulfonate derivatives are an essential class of compounds with diverse pharmacological applications. This study presents the synthesis and detailed characterization of six novel Schiff base sulfonate derivatives (L-L) through spectroscopic techniques (FT-IR and NMR). Their inhibitory potential was evaluated against human carbonic anhydrase isoenzymes (hCA I and hCA II) and acetylcholinesterase (AChE), which are crucial therapeutic targets for diseases such as glaucoma, epilepsy, and Alzheimer's disease. The K values for the compounds concerning AChE, hCA I, and hCA II enzymes were in the ranges of 106.10 ± 14.73 to 422.80 ± 17.64 nM (THA: 159.61 ± 8.41 nM), 116.90 ± 24.40 to 268.00 ± 35.84 nM (AAZ: 439.17 ± 9.30 nM), and 177.00 ± 35.03 to 435.20 ± 75.98 nM (AAZ: 98.28 ± 1.69 nM), respectively. Molecular docking analyses revealed key interactions within the active sites of the enzymes, including hydrogen bonding with critical residues and π-π stacking interactions. Notably, L demonstrated superior inhibition against hCA I (K: 116.90 ± 24.40 nM) and AChE (K: 106.10 ± 14.73 nM), positioning it as a promising lead compound. This comprehensive investigation contributes to the development of isoform-specific inhibitors for therapeutic use and provides valuable insights into their binding mechanisms. The findings underscore the potential of Schiff base sulfonates as scaffolds in drug discovery for neurodegenerative and metabolic disorders.
磺酸盐衍生物是一类具有多种药理应用的重要化合物。本研究通过光谱技术（傅里叶变换红外光谱和核磁共振）介绍了六种新型席夫碱磺酸盐衍生物（L-L）的合成及详细表征。评估了它们对人碳酸酐酶同工酶（hCA I和hCA II）以及乙酰胆碱酯酶（AChE）的抑制潜力，这些酶是青光眼、癫痫和阿尔茨海默病等疾病的关键治疗靶点。化合物针对AChE、hCA I和hCA II酶的K值分别在106.10±14.73至422.80±17.64 nM（THA：159.61±8.41 nM）、116.90±24.40至268.00±35.84 nM（AAZ：439.17±9.30 nM）和177.00±35.03至435.20±75.98 nM（AAZ：98.28±1.69 nM）范围内。分子对接分析揭示了酶活性位点内的关键相互作用，包括与关键残基的氢键和π-π堆积相互作用。值得注意的是，L对hCA I（K：116.90±24.40 nM）和AChE（K：106.10±14.73 nM）表现出卓越的抑制作用，使其成为一种有前景的先导化合物。这项全面的研究有助于开发用于治疗的同工酶特异性抑制剂，并为其结合机制提供有价值的见解。研究结果强调了席夫碱磺酸盐作为神经退行性和代谢性疾病药物发现支架的潜力。
