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Synthesis and In silico Studies of Quinazolinone Derivatives as PARP-1 Inhibitors



 Cancer is a leading cause of deaths worldwide, accounting for 9.6 million
deaths in 2018. According to the WHO, the most common causes of cancer deaths are lung, colorectal,
stomach liver and breast cancer.



 PARP-1 has a crucial role in cell proliferation, survival and death due to its role in the regulation
of multiple biological processes. Quinazolinone and its derivatives represent a large class of biologically
active compounds that exhibit a broad spectrum of biological activities such as anti-HIV, anticancer, antifungal,
antibacterial, anticonvulsant, anti-inflammatory, antidepressant, antimalarial, antioxidant and antileishmanial
activities.



 In this study, we have synthesized quinazolinone derivatives by reaction of 2-
aminobenzamide and substituted benzaldehydes. The synthesized compounds were also screened in
silico for their PARP-1 binding affinities by molecular docking studies using Schrodinger 2016
software. In silico ADME studies were also performed for the synthesized compounds by using
QikProp tool of Schrodinger software.



Results of in silico studies indicated that quinazolinone derivatives exhibited a good affinity
towards the active site of PARP-1. Out of all synthesized compounds, SVA-11 exhibited a maximum
dock score (-10.421). Results of ADME studies indicated the suitability of synthesized compounds
as drug candidates.



The synthesized compounds showed better docking scores than reference drug valiparib.
Furthermore, they exhibited favorable ADME profile. Therefore, they may serve as lead compounds
in the discovery of PARP-1 inhibitors.
