Carbonic Anhydrase Inhibitors: Identifying Therapeutic Cancer Agents Through Virtual Screening

Computer-aided drug design includes an ensemble of different in silico strategies that represent valuable tools for facilitating the discovery and optimization of novel hit compounds endowed with biological activity toward the desired target proteins. Due to the various pathological implications of carbonic anhydrases (CAs), especially in the development and progression of cancer, molecular modeling techniques have been widely applied for the identification of new CA inhibitors. In this chapter, after providing the reader with a brief introduction to computational methods in drug design, we summarize the results of the main virtual screening (VS) studies that led to the discovery of novel ligands of different CA isoforms, describing the various receptor-based and ligand-based approaches employed. Moreover, we report the results of retrospective analyses in which CAs and their known ligands have been used to validate the performance of various VS methods in hit identification. The present chapter should provide the reader with a panoramic view of the most used and reliable in silico techniques to be applied in the search for novel CA inhibitors.