Drug Designing and Development Approaches Carbonic Anhydrase Ix As Anticancer Agent

Abstract

Carbonic anhydrase IX is an enzyme expressed by the gene CA9 in humans. Carbonic anhydrase enzymes are involved in the interconversion of carbon dioxide and water molecule into carbonic acid, protons and ions of bicarbonate. This isoform of carbonic anhydrase IX is a trans membrane dimeric metalloenzyme possessing an extracellular active site which facilitates acid secretion in gastrointestinal tract. This enzyme is hypoxia inducible and is overexpressed in the some types of tumors. Carbonic anhydrase IX is overexpressed in many cancer types such as renal cell carcinoma, carcinomas of cervix, breast and also the carcinoma of lungs. Carbonic anhydrase IX inhibitors includes various class of drugs and they work by various mechanism of actions which includes chelation of bivalent ion of the active site, anchoring of compound with the zinc coordinated water molecule or hydroxide ion, compounds which procures enterance the active site, etc. The drug classes such as sulfonamides, coumarins, sulfamates and sulfamides, phenols, carboxylic acids, monoclonl antibodies are widely used for the inhibition of carbonic anhydrase IX and thus for the treatment of cancer.