TY  - JOUR
TI  - In silico Repurposing of Drugs for pan-HDAC and
pan-SIRT Inhibitors: Consensus Structure-based
Virtual Screening and Pharmacophore Modeling
Investigations
AB  - Objectives: 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.
Materials and Methods: 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.
Results: 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.
Conclusion: 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 SIRTrelated
diseases but also provides insights for designing potent de novo derivatives.
AU  - AVCI, Ahmet
AU  - SARI, SUAT
AU  - Kocak Aslan, Ebru
DO  - 10.4274/tjps.galenos.2021.25564
PY  - 2021
JO  - Turkish Journal of Pharmaceutical Sciences
VL  - 18
IS  - 6
SN  - 1304-530X
SP  - 730
EP  - 737
DB  - TRDizin
UR  - http://search/yayin/detay/523281
ER  -