Department of Chemical Sciences, National Institute of Pharmaceutical Education and Research (NIPER), Balanagar, Hyderabad, Telangana, India.
Department NEUROFARBA, Pharmaceutical and Nutraceutical Section, University of Florence, Sesto Fiorentino (Florence), Italy.
Arch Pharm (Weinheim). 2023 Nov;356(11):e2300309. doi: 10.1002/ardp.202300309. Epub 2023 Sep 10.
Herein, we report the design and synthesis of two series of pyrazole-tethered sulfamoyl phenyl acetamides and pyrazole-tethered sulfamoyl phenyl benzamides. The synthesized compounds were investigated for inhibiting two human carbonic anhydrases, human carbonic anhydrases (hCA) I and II, and those of the bacterial pathogen Mycobacterium tuberculosis, mtCA 1-3. The results indicate that, among the synthesized compounds, pyrazoles with 4-aminobenzene sulfonamide were more selective toward hCA I and II over mtCAs, and compounds with 3-aminobenzene sulfonamide were selective toward mtCA 1-3 over hCA I, II. Compound 6g showed significant and selective inhibition toward hCA I and II, with K values of 0.0366 and 0.0310 µM, respectively. Compound 5g exhibited the best inhibition toward mtCA 2, with a K value of 0.0617 µM. Among the benzamides, compound 9b exhibited significant activity toward mtCA 2, with a K value of 0.0696 µM. Selectivity of these compounds was further supported by docking studies. When tested for antitubercular activity, many compounds showed moderate to good inhibition against the Mtb H37Rv strain, with minimum inhibitory concentration (MIC) values in the range of 4-128 µg/mL.
本文报道了一系列吡唑连接的磺酰胺基苯乙酰胺和吡唑连接的磺酰胺基苯甲酰胺的设计与合成。研究了这些合成化合物对两种人碳酸酐酶（人碳酸酐酶 I 和 II）和细菌病原体结核分枝杆菌（mtCA）1-3 的抑制作用。结果表明，在所合成的化合物中，4-氨基苯磺酰胺取代的吡唑对 hCA I 和 II 的选择性高于 mtCAs，而 3-氨基苯磺酰胺取代的吡唑对 mtCA 1-3 的选择性高于 hCA I 和 II。化合物 6g 对 hCA I 和 II 表现出显著的选择性抑制作用，K i 值分别为 0.0366 和 0.0310µM。化合物 5g 对 mtCA 2 的抑制作用最佳，K i 值为 0.0617µM。在苯甲酰胺中，化合物 9b 对 mtCA 2 表现出显著的活性，K i 值为 0.0696µM。这些化合物的选择性进一步得到了对接研究的支持。在抗结核活性测试中，许多化合物对 Mtb H37Rv 菌株表现出中等至良好的抑制作用，最低抑菌浓度（MIC）值在 4-128µg/mL 范围内。
