Synthesis and In Silico Studies of Quinazolinones as PARP-1 Inhibitors

Maneesh Guleria; Adarsh Kumar; Ankit Kumar Singh; Pradeep Kumar

doi:10.2174/1386207326666230905153443

Synthesis and In Silico Studies of Quinazolinones as PARP-1 Inhibitors

Comb Chem High Throughput Screen. 2023 Sep 5. doi: 10.2174/1386207326666230905153443. Online ahead of print.

Authors

Maneesh Guleria^{1

2}, Adarsh Kumar¹, Ankit Kumar Singh¹, Pradeep Kumar¹

Affiliations

¹ Department of Pharmaceutical Sciences and Natural Products, Central University of Punjab, Bathinda, India -151401.
² Department of Pharmaceutical Sciences and Technology, Maharaja Ranjit Sigh Punjab Technical University, Bathinda, India -151001.

PMID: 37691193
DOI: 10.2174/1386207326666230905153443

Abstract

Background: Cancer is a leading threat to humankind, accounting for nearly one million deaths in 2018, and the expected number of cancer-related deaths in 2040 is more than 16 million. The most common causes of cancer deaths are lung, colorectal, stomach, liver and breast cancer, while the highest number of new cancer cases belong to lung, breast, colorectal, prostate, stomach and liver cancer.

Introduction: PARP-1 is an enzyme that plays an important role in DNA repair, cell propagation/survival and death due to its influence on numerous biological processes. Quinazolinones represent an important scaffold in medicinal chemistry and have a broad spectrum of biological activities.

Method: In this study, we have synthesized quinazolinones by reaction of 2-aminobenzamide and substituted aldehydes. Molecular docking studies of synthesized compounds were performed for their PARP-1 binding affinities using Schrodinger 2016 software. In silico ADME studies were also performed for the synthesized compounds using the QikProp tool of Schrodinger software.

Results: Results of molecular docking studies indicated that synthesized quinazolinones had a good affinity towards active site of PARP-1 and compound 4 had the best docking score (-10.343). Results of ADME studies indicated the drug-like properties of synthesized compounds, which make them suitable drug candidates.

Conclusion: All the synthesized compounds have a better docking score than niraparib (-9.05). Further, the synthesized compounds have a favorable ADME profile. Therefore, they may serve as important leads in discovering PARP-1 inhibitors.

Keywords: ADME; Cancer; PARP-1; molecular docking studies; quinazolinones.