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

Author(s): Sonia Verma, Akashdeep Singh Pathania, Somesh Baranwal, Pradeep Kumar*

Journal Name: Letters in Drug Design & Discovery

Volume 17 , Issue 12 , 2020


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Abstract:

Background: 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.

Introduction: 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.

Methods: 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: 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.

Conclusion: 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.

Keywords: Cancer, PARP-1, quinazolinone, in silico, docking, ADME.

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Article Details

VOLUME: 17
ISSUE: 12
Year: 2020
Published on: 19 July, 2020
Page: [1552 - 1565]
Pages: 14
DOI: 10.2174/1570180817999200719152959
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