Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Ataturk University, Erzurum, Turkey.
Department of Chemistry, Faculty of Science, Ataturk University, Erzurum, Turkey.
Arch Pharm (Weinheim). 2021 Jan;354(1):e2000243. doi: 10.1002/ardp.202000243. Epub 2020 Sep 28.
A novel series of sulfonamides, 4-(3-phenyltriaz-1-en-1-yl)-N-(4-methyl-2-pyrimidinyl)benzenesulfonamides (1-9), was designed and synthesized by the diazo reaction between sulfamerazine and substituted aromatic amines for the first time. Their chemical structures were characterized by H nuclear magnetic resonance (NMR), C NMR, and high-resolution mass spectra. The newly synthesized compounds were evaluated in terms of acetylcholineasterase (AChE) and human carbonic anhydrases (hCA) I and II isoenzymes inhibitory activities. According to the AChE inhibition results, the K values of the compounds 1-9 were in the range of 19.9 ± 1.5 to 96.5 ± 20.7 nM against AChE. Tacrine was used as the reference drug and its K value was 49.2 ± 2.7 nM against AChE. The K values of the compounds 1-9 were in the range of 10.2 ± 2.6 to 101.4 ± 27.8 nM against hCA I, whereas they were 18.3 ± 4.4 to 48.1 ± 4.5 nM against hCA II. Acetazolamide was used as a reference drug and its K values were 72.2 ± 5.4 and 52.2 ± 5.7 nM against hCA I and hCA II, respectively. The most active compounds, 1 (nonsubstituted) against AChE, 5 (4-ethoxy-substituted) against hCA I, and 8 (4-bromo-substituted) against hCA II, were chosen and docked at the binding sites of these enzymes to explain the inhibitory activities of the series. The newly synthesized compounds presented satisfactory pharmacokinetic properties via the estimation of ADME properties.
首次通过重氮反应将磺胺甲恶唑与取代芳胺偶联，设计并合成了一系列新型磺酰胺类化合物 4-(3-苯并三唑-1-烯-1-基)-N-(4-甲基-2-嘧啶基)苯磺酰胺（1-9）。通过 1H 核磁共振（NMR）、13C NMR 和高分辨质谱对其化学结构进行了表征。根据乙酰胆碱酯酶（AChE）和人碳酸酐酶（hCA）I 和 II 同工酶抑制活性评价了新合成的化合物。根据 AChE 抑制结果，化合物 1-9 对 AChE 的 K 值范围为 19.9±1.5 至 96.5±20.7 nM。他克林被用作参考药物，其对 AChE 的 K 值为 49.2±2.7 nM。化合物 1-9 对 hCA I 的 K 值范围为 10.2±2.6 至 101.4±27.8 nM，而对 hCA II 的 K 值范围为 18.3±4.4 至 48.1±4.5 nM。乙酰唑胺被用作参考药物，其对 hCA I 和 hCA II 的 K 值分别为 72.2±5.4 和 52.2±5.7 nM。选择最活跃的化合物 1（未取代）对抗 AChE、5（4-乙氧基取代）对抗 hCA I 和 8（4-溴取代）对抗 hCA II，并将其对接在这些酶的结合位点上，以解释该系列的抑制活性。通过估计 ADME 性质，新合成的化合物表现出令人满意的药代动力学特性。
