Abstract

Background: Compound containing sulfonamide, pyrazole and chalcone groups are important in medicinal chemistry. They have a wide range of biological activities, including carbonic anhydrase (CA) inhibitory activities.

Introduction: Carbonic anhydrase I and II inhibitors are used for the treatment of diseases, such as retinal and cerebral edema (CA I), epilepsy, and glaucoma (CA II). However, the currently available drugs have some limitations or side effects. Thus, there is a need for new drug candidates to overcome these issues. In this study, a series of compounds, (E)-4-(4-(3-aryl)-3-oxoprop-1-en-1-yl)- 3-phenyl-1H-pyrazol-1-yl) benzenesulfonamides MS4-MS10, were designed to discover new CA inhibitors using a hybrid approach.

Methods: Compounds MS4-MS10 were synthesized as shown in Scheme 1, and their chemical structures were confirmed by ¹H NMR, ¹³C NMR, and HRMS spectra. The CAs (E.C.4.2.1.1) inhibitory effects of MS4-MS10 were tested on the hCA I and II isoenzymes using previously reported procedures.

Results: The CA inhibitors MS4–MS10 gave IC₅₀ values (nM) of 27.8–87.3 towards hCA I and 24.4–54.8 towards hCA II while the IC₅₀ values for reference drug acetazolamide were 384.2 (hCA I) and 36.9 (hCA II). MS7 and MS9 exhibited 13.8 (hCA I) and 1.5 (hCA II) times more potent CA inhibition than the reference compound acetazolamide, respectively.

Conclusion: MS7 (Ar: 2,4,5-trimethoxy phenyl) and MS9 (Ar: 3,4-dimethoxy phenyl) were the most promising compounds of our series with the lowest IC₅₀ values towards hCA I and hCA II, respectively, and can be considered for further studies.

Keywords: Pyrazoline, sulfonamides, chalcone, carbonic anhydrase isoenzymes, IC₅₀, synthesis.

Graphical Abstract