Abstrakt

Discovery of curcumin heterocyclics containing sulphonamides for carbonic anhydrase inhibition and molecular docking studies

Dr. Mahmood Ahmed

Curcumin is a multi-functional pharmacologically safe natural agent with proven cytoprotective effects to healthy human cells. In this study, a new series of 22 sulfonamides with curcumin scaffold were synthesized, characterized and investigated for their carbonic anhydrase isoenzyme I (human) and II (bovine) isoforms. The structures of newly synthesized compounds were described by IR, 1H NMR and 13C NMR spectral data. Curcumin-isoxazole conjugated sulfonamide showed the Ki value of 0.99 µM with highest inhibitory activity among all other synthesized compounds against hCA-I enzyme. Similarly enzyme kinetic studies of compounds like curcumin-isoxazole, curcumin-pyrazole, and curcumin-pyrimidine conjugated sulfonamide against bCAII enzyme showed Ki values of 0.71, 0.67 and 0.71 µM respectively. Our biological assays results showed that most of active compounds have similar inhibitory activities compared to standard acetazolamide drug. The molecular docking predicted binding modes showed that these compounds bind with hCA-1 enzyme in similar fashion.