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- MakaleAçık Erişim2025Novel Sulfonylhydrazones With Sulfonate Ester Framework: Promising Dual Inhibitors of AChE and hCAs
Öztürk, Cansu; Balci, Neslihan; Aslan, Osman Nuri; Kalay, Erbay
Alzheimer's disease (AD) is a progressive neurodegenerative disorder that affects millions of individuals worldwide. Treatment strategies for AD vary depending on cognitive and behavioral symptoms, with cholinergic replacement therapy using acetylcholinesterase (AChE) inhibitors being one of the primary approaches. Recent studies have also identified human carbonic anhydrases (hCAs) as significant therapeutic targets for AD, offering new opportunities for the development of innovative treatments. Carbonic anhydrase inhibitors have been shown to prevent early mitochondrial damage and inhibit H2O2 production, thereby reducing amyloid plaque formation. Building on the promising potential of hydrazones particularly sulfonyl hydrazones as anticholinesterase agents, we synthesized 12 novel chlorine-substituted sulfonyl hydrazone compounds containing aryl sulfonate ester groups. These compounds were evaluated for their inhibitory effects on AChE, hCA I, and hCA II enzymes. The synthesized compounds exhibited low nanomolar inhibitory activity, with Ki values ranging from 9.58 ± 2.22 to 104.04 ± 23.82 nM for AChE, 9.12 ± 2.21 to 477.63 ± 218.52 nM for hCA I, and 17.54 ± 7.74 to 564.62 ± 213.98 nM for hCA II. Notably, compound 6 showed strong inhibitory activity against hCA I (Ki = 9.12 ± 2.21 nM; acetazolamide (AZA) = 26.54 ± 3.11 nM) and hCA II (Ki = 17.54 ± 7.74 nM; AZA = 21.73 ± 2.42 nM), whereas compound 4 exhibited superior AChE inhibition (Ki = 9.58 ± 2.22 nM; TAC = 23.12 ± 2.05 nM). The chemical structures of the synthesized compounds were characterized using advanced spectroscopic techniques, including FT-IR, 1H-NMR, and 13C-NMR spectroscopy.
- MakaleYalnız künye2024Sulfonamide derivatives with benzothiazole scaffold: Synthesis and carbonic anhydrase I–II inhibition properties
Öztürk, Cansu; Kalay, Erbay; Gerni, Serpil; Balci, Neslihan; Tokali, Feyzi Sinan; Aslan, Osman Nuri; Polat, Emrah
The secondary sulfonamide derivatives containing benzothiazole scaffold (1–10) were synthesized to determine their inhibition properties on two physiologically essential human carbonic anhydrases isoforms (hCAs, EC, 4.2.1.1), hCA I, and hCA II. The inhibitory effects of the compounds on hCA I and hCA II isoenzymes were investigated by comparing their IC50 and Ki values. The Ki values of compounds (1–10) against hCA I and hCA II are in the range of 0.052 ± 0.022–0.971 ± 0.280 and 0.025 ± 0.010–0.682 ± 0.335, respectively. Some of these inhibited the enzyme more effectively than the standard drug, acetazolamide. In particular, compounds 5 and 4 were found to be most effective on hCA I and hCA II.