Design of effective carbonic anhydrase inhibitors by using in silico pharmacophore analysis

Pharmacophore modeling is a successful yet very diverse subfield of computer-aided drug design. The concept of the pharmacophore has been widely applied to the rational design of novel drugs. In this paper, we review the computational implementation of this concept and its common usage in the drug discovery process. Carbonic anhydrases (CAs) are zinc containing metalloenzymes including sixteen different isoforms. These enzymes differ in their subcellular localization, catalytic activity and susceptibility to different classes of inhibitors. The previous studies have also indicated that the CA I and II levels were also higher in several cancer types, such as higher cytosolic erythrocte levels in stomach, prostate, lung and ovary tumors; also in hematological diseases such as leukemia. In addition, CA II has come to the forefront by being expressed in the endothelium of neovessels in some cancer tissues, including melanoma, esophageal, renal cancers. Therefore, it is aimed to investigate and design reliable and potential carbonic anhydrase inhibitors against to multi target; CA I and II by using biological data from our team for treatment of cancer.