From Homology Modeling to the Hit Identification and Drug Repurposing: A Structure-Based Approach in the Discovery of Novel Potential Anti-Obesity Compounds

• Published in: Methods in molecular biology (Clifton, N.J.) Vol. 2266; p. 263
• Main Authors: Costa, Giosuè, Artese, Anna, Ortuso, Francesco, Alcaro, Stefano
• Format: Journal Article
• Language: English
• Published: United States 2021
• Subjects: Anti-Obesity Agents - chemistry; Carbonic Anhydrase Inhibitors - chemistry; Drug Design; Drug Repositioning - methods; In Vitro Techniques; Ligands; Models, Chemical; Molecular Docking Simulation - methods; Molecular Dynamics Simulation; Molecular Structure; Small Molecule Libraries; Software; Structure-Activity Relationship; Anti-obesity drugs; Drug repurposing; Virtual screening; Drug design; Selectivity; Carbonic anhydrase VA; Molecular docking
• ISSN: 1940-6029
• DOI: 10.1007/978-1-0716-1209-5_15

Although science and technology have progressed rapidly, de novo drug development has been a costly and time-consuming process over the past decades. In this scenario, drug repurposing has appeared as an alternative tool to accelerate the drug development process. Herein, we applied such an approach to the highly popular human Carbonic Anhydrase (hCA) VA drug target, that is involved in ureagenesis, gluconeogenesis, lipogenesis, and in the metabolism regulation. Albeit several hCA inhibitors have been designed and are currently in clinical use, serious drug interactions have been reported due to their poor selectivity. In this perspective, the drug repurposing approach could be a useful tool for investigating the drug promiscuity/polypharmacology profile. In this chapter, we describe a combination of virtual screening techniques and in vitro assays aimed to identify novel selective hCA VA inhibitors and to repurpose drugs known for other clinical indications.