In the design and discovery of anticancer drugs, various natural heterocyclic scaffolds have attracted considerable interest as privileged structures. For rational drug design, some of the natural scaffolds such as chromones have exhibited wide acceptability due to their drug-like properties. Among the approved anticancer drugs, the scaffolds with high selectivity for a small group of closely related targets are of importance. In the development of selective anticancer agents, the natural, as well as synthetic, can generate highly selective compounds toward cancer targets. The present manuscript includes more particularly the development of cancer inhibitors incorporating the chromone scaffold, with a strong emphasis on their molecular interactions in the anticancer mechanism. It also includes the structure-activity relationship studies and related examples of lead optimization.
Recent global outbreak of the pandemic caused by coronavirus (COVID-19) emphasizes the urgent need for novel antiviral therapeutics. It can be supplemented by utilization of efficient and validated drug discovery approaches such as drug repurposing/repositioning. The well reported and clinically used anti-malarial aminoquinoline drugs (chloroquine and hydroxychloroquine) have shown potential to be repurposed to control the present pandemic by inhibition of COVID-19. The review elaborates the mechanism of action, safety (side effects, adverse effects, toxicity) and details of clinical trials for chloroquine and hydroxychloroquine to benefit the clinicians, medicinal chemist, pharmacologist actively involved in controlling the pandemic and to provide therapeutics for the treatment of COVID-19 infection. 2. Mechanism of action For viral replication, a stable acidic pH of endosomes, lysosomes, Golgi complex of host is required. The bioaccumulation properties of both the selected aimnoquinolines explain the antiviral mechanism of their action [108]. Chloroquine increases the pH of intracellular vacuoles. In lysosomes, it alters the catalysis of the protein degradation pathways through acidic hydrolases. It also alters endosomal
Hepatitis C virus (HCV) infection has emerged as one of the most significant disease to affect humans. Despite its large medical and economical impact, there are no vaccines or efficient therapies without major side effects. The HCV non-structural protein 5B (NS5B) is the RNA-dependent RNA polymerase responsible for the complete copy of the RNA viral genome and is a target of choice for the development of anti-HCV drugs. Although many small molecules have been identified as allosteric inhibitors of NS5B, very few are active in clinical applications. Developments in the field have prompted us to review the research work on HCV NS5B polymerase inhibitors, especially their structure activity relationships and molecular modeling studies. This review will focus on the journey of drug discovery of HCV NS5B inhibitors covering both nucleoside and non-nucleosides.
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