Abstract
Nowadays the determination of inhibitors of carbonic anhydrase isoenzymes (CAs) have become one of the main goals of drug design studies, and inhibitors of CAs have taken their place in clinical applications to be used in the treatment and diagnosis of many diseases from glaucoma to cancer. On the other hand, acetylcholinesterase (AChE) inhibitors are also the main target molecules for the treatment of Alzheimer's disease. However, the unwanted side effects of existing CA and AChE inhibitors necessitate the identification of new and selective inhibitors of these enzymes. In this study, we examined the inhibition effects of some natural antiproliferative agents on CA-I, CA-II, and AChE activities isolated from human erythrocytes. Betulinic acid (I) had the strongest inhibitory effect on esterase activity of hCA-I (IC50 29.16 mu M) and hCA-II (IC50 31.82 mu M). On the other hand, sanguinarine chloride (VI) had the strongest inhibitory effect (IC50: 19.44 mu M) on hAChE activity. Molecular modeling studies were also carried out to elucidate the inhibition mechanism of betulinic acid on hCA-I and hCA-II isoenzymes and sanguinarine chloride on the hAChE enzyme. We believe that the results we obtained in this study will contribute to the design of new and natural CA and AChE inhibitors.
NSTL