Inhibitory effects of quercetin and resveratrol and their sulfonamide derivatives on the carbonic anhydrase activity: spectroscopic studies of the binding process

Carbonic anhydrase (CA) isozymes participate in numerous pathological and physiological pathways. In this research, sulfonamide derivatives (QD and RD) of polyphenolic compounds quercetin (Q) and resveratrol (R) were chemically synthesized and their interaction with hCA II and CA IX isozymes was investigated. Data collection was performed experimentally using spectroscopic methods. As a result, all compounds were generally effective low micromolar CA competitive inhibitors. Among them, the sulfonamide derivative of quercetin (QD) had the lowest IC50 value (5.13 +/- 0.24 mu M) for the hCA II, which was lower than that of CA IX (28.52 +/- 0.12 mu M). Concerning the hCA II isozyme, the calculated Ki values for Q, QD, R, and RD compounds were 5.43 +/- 0.65, 3.42 +/- 0.26, 455.00 +/- 12.02 and 242.50 +/- 18.38 mu M, respectively. Also, fluorescence measurements showed dynamic quenching of the hCA II intrinsic fluorescence. Moreover, evaluation of the thermodynamic parameters involved in binding revealed that both hydrogen bonds and van der Waals interactions are crucial in the interaction between these compounds and the hCA II isozyme. Fluorescence analysis of the CAII-DNSA fluorescent complex in different concentrations of Q, QD, R, and RD compounds showed the lowest dissociation constant (Kd) for the QD, indicating that this compound has a higher affinity for binding to the hCA II isozyme. Overall, the strengthening of the binding power and inhibitory activity of RD and QD for the hCA II and CA IX as compared to Q and R paves the way for the development of novel hCA inhibitors through the use of these derivatives.