Author:

Keywords:

Science & Technology, Life Sciences & Biomedicine, Chemistry, Medicinal, Pharmacology & Pharmacy, DNA TOPOISOMERASE-II, VIRAL DIARRHEA VIRUS, DEHYDROGENASE, RIBAVIRIN, MODEL, DISCOVERY, PROTEIN, AGENTS, Acridines, Acridones, Antiviral Agents, Hepacivirus, Hepatitis C, Humans, RNA Helicases, Structure-Activity Relationship, Viral Nonstructural Proteins, Virus Replication, 0304 Medicinal and Biomolecular Chemistry, 0305 Organic Chemistry, 1115 Pharmacology and Pharmaceutical Sciences, Medicinal & Biomolecular Chemistry, 3214 Pharmacology and pharmaceutical sciences, 3404 Medicinal and biomolecular chemistry, 3405 Organic chemistry

Abstract:

We report the synthesis and structure-activity relationship (SAR) of a large series of acridones and acridone-fragment derivatives designed on the basis of the selective antihepatitis C virus (HCV) activity shown by acridone 2, previously studied as a potential antibovine viral diarrhea virus (BVDV) compound. The evaluation of their ability to inhibit the HCV replication in Huh-5-2 cells led to the identification of new, selective inhibitors. This indicates that the acridone skeleton, when properly functionalized, is a suitable scaffold to obtain potential anti-HCV agents. Interestingly, during identification of possible cellular and viral targets, it was discovered that compound 23 exerts inhibitory activity on the HCV NS3 helicase, a very promising target for the development of anti-HCV drugs.