Title:In Silico Discovery of Novel Flavonoids as Poly ADP Ribose Polymerase (PARP) Inhibitors
Volume: 17
Issue: 3
Author(s): Ashish Shah*, Ghanshyam Parmar and Avinash Kumar Seth
Affiliation:
- Department of Pharmacy, Drug Discovery Lab, Sumandeep Vidyapeeth, Vadodara-391760, Gujarat,India
Keywords:
Virtual screening, Flavonoids, NPACT database, PARP inhibitors, re-docking, polymerase.
Abstract:
Background: The concept of synthetic lethality is an emerging field in the treatment of
cancer and can be applied for new drug development of cancer as already been represented by Poly
(ADP-ribose) polymerase (PARPs) inhibitors.
Objective: In this study, we performed virtual screening of 329 flavonoids obtained from the 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 include
molecular docking studies, prediction of drug-likeness 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. The accuracy of the 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 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.
