{Reference Type}: Journal Article
{Title}: In silico Repurposing of Drugs for pan-HDAC and pan-SIRT Inhibitors: Consensus Structure-based Virtual Screening and Pharmacophore Modeling Investigations.
{Author}: Sarı S;Avci A;Koçak Aslan E;
{Journal}: Turk J Pharm Sci
{Volume}: 18
{Issue}: 6
{Year}: Dec 2021 31
暂无{DOI}: 10.4274/tjps.galenos.2021.25564
{Abstract}: <B>OBJECTIVE: </B>Drug repurposing is a highly popular approach to find new indications for drugs, which greatly reduces time and costs for drug design and discovery. Non-selective inhibitors of histone deacetylase (HDAC) isoforms including sirtuins (SIRTs) are effective against conditions like cancer. In this study, we used molecular docking to screen Food and Drug Administration (FDA)-approved drugs to identify a number of drugs with a potential to be repurposed for pan-HDAC and pan-SIRT inhibitor activity.<BR><B>METHODS: </B>The library of FDA-approved drugs was optimized using MacroModel. The crystal structures of HDAC1-4, 6-8, SIRT1-3, 5, 6 were prepared before the library was docked to each structure using Glide, FRED, and AutoDock Vina/PyRx. Consensus scores were derived from the docking scores obtained from each software. Pharmacophore modeling was performed using Phase.<BR><B>RESULTS: </B>Based on the consensus scores, belinostat, bexarotene, and cianidanol emerged as top virtual pan-HDAC inhibitors whereas alosetron, cinacalcet, and indacaterol emerged as virtual pan-SIRT inhibitors. Pharmacophore hypotheses for these virtual inhibitors were also suggested through pharmacophore modeling in agreement with the molecular docking models.<BR><B>CONCLUSIONS: </B>The consensus approach enabled selection of the best performing drug molecules according to different software, and good scores against isoforms (virtual pan-HDAC and pan-SIRT inhibitors). The study not only proposes potential drugs to be repurposed for HDAC and SIRT-related diseases but also provides insights for designing potent de novo derivatives.