Exploration of 3‐aryl pyrazole‐tethered sulfamoyl carboxamides as carbonic anhydrase inhibitors

Abstract

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 Ki values of 0.0366 and 0.0310 µM, respectively. Compound 5g exhibited the best inhibition toward mtCA 2, with a Ki value of 0.0617 µM. Among the benzamides, compound 9b exhibited significant activity toward mtCA 2, with a Ki 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.

Benzothiadiazinone-1,1-Dioxide Carbonic Anhydrase Inhibitors Suppress the Growth of Drug-Resistant Mycobacterium tuberculosis Strains

“…The aim was to unveil the relationship between the structural features and the inhibitory profile of the ligands. As the 3D-solved structure of MtCA3 is currently unavailable, we utilized the homology model (HM) previously built in our previous investigations [ 56 , 57 ].…”

Antitubercular activity of 2-mercaptobenzothiazole derivatives targeting Mycobacterium tuberculosis type II NADH dehydrogenase

“…To determine the MIC of the synthesized compounds, the liquid broth micro-dilution method was used in 96-well round bottom microtiter plates (Corning, USA) as mentioned in ref. 29. Briefly, the bacterial cultures were grown to a mid-log phase ( i.e.…”