Background:
The concept of synthetic lethality is emerging field in the treatment of cancer and
can be applied for new drug development of cancer as it has been already represented by Poly
(ADP-ribose) polymerase (PARPs) inhibitors.
Objectives:
In this study we performed virtual
screening of 329 flavonoids obtained from Naturally Occurring Plant-based Anti-cancer
Compound-Activity-Target (NPACT) database to identify novel PARP inhibitors.
Materials and methods:
Virtual screening carried out using different In Silico methods which includes
molecular docking studies, prediction of druglikeness and In Silico toxicity studies.
Results:
Fifteen out of 329 flavonoids achieved better docking score as compared to rucaparib
which is an FDA approved PARP inhibitor. These 15 hits were again rescored using accurate
docking mode and drug-likeliness properties were evaluated. Accuracy of docking method was
checked using re-docking. Finally NPACT00183 and NPACT00280 were identified as potential
PARP inhibitors with docking score of -139.237 and -129.36 respectively. These two flavonoids
were also showed no AMES toxicity and no carcinogenicity which was predicted using
admetSAR.
Conclusion:
Our finding suggests that NPACT00183 and NPACT00280 have
promising potential to be further explored as PARP inhibitors.
