Synthesis, cytotoxicities, and carbonic anhydrase inhibition activities of pyrazoline-benzenesulfonamide derivatives harboring phenol/polyphenol moieties

In this study, phenol and benzenesulfonamide substituted pyrazoline derivative novel compounds (1a-14a) were synthesized successfully for the first time (except 3a, 8a, 13a, and 14a) by microwave irradiation method. The chemical structures of the newly synthesized compounds were confirmed and characterized by H-1 NMR, C-13 NMR, and HRMS spectra. Carbonic anhydrase inhibitory effects and cytotoxic activities of the synthesized compounds were studied and reported to find out new possible drug candidate molecules. The carbonic anhydrase (CA) inhibition results of the compounds 1a-14a revealed Ki values in the range of 7.53 +/- 0.91-58.26 +/- 9.61 nM towards hCA I while 8.49 +/- 1.45-33.35 +/- 3.22 nM towards hCA II. On the other hand, Ki values of the reference drug acetazolamide (AZA) were 68.13 +/- 9.11 nM and 48.13 +/- 8.28 nM towards hCA I and hCA II, respectively. Thus, all synthesized compounds 1a-14a had higher inhibitory activities towards both hCA I and hCA II than AZA. According to the cytotoxicity results of the compounds 1a-14a, all compounds resulted in 50% inhibition of the malignant cell proliferation at low micromolar concentrations. The cytotoxicity results suggested that compounds 3a, 5a, and lla had both high tumor-selectivity and cytotoxicity and were considered as lead compounds for further studies in terms of their anticancer activity. [GRAPHICS] .