Issue 49, 2020

Design, synthesis and in silico studies of new quinazolinone derivatives as antitumor PARP-1 inhibitors

Abstract

Herein, we report an eco-friendly synthesis of a new series of quinazolinone-based derivatives as potential PARP-1 inhibitors. The 4-quinazolinone scaffold was utilized as a bioisostere to the phthalazinone core of the reference compound Olaparib. Most of the synthesized compounds displayed appreciable inhibitory activity against PARP-1. Compound 12c showed inhibitory activity at IC50 = 30.38 nM comparable to Olaparib, which has IC50 = 27.89 nM. Cell cycle analysis was performed for compounds 12a and 12c, and both exhibited cell growth arrest at G2/M phase in the MCF-7 cell line. In addition, both compounds increased the programmed apoptosis compared to the control. Furthermore, molecular docking of the final compounds into the PARP-1 active site was executed to explore their probable binding modes. Also, a computational QSAR and in silico ADMET study was performed. The results of this study revealed that some of the newly synthesized compounds could serve as a new framework to discover new PARP-1 inhibitors with anti-cancer activity.

Graphical abstract: Design, synthesis and in silico studies of new quinazolinone derivatives as antitumor PARP-1 inhibitors

Supplementary files

Article information

Article type
Paper
Submitted
07 7 2020
Accepted
27 7 2020
First published
10 8 2020
This article is Open Access
Creative Commons BY-NC license

RSC Adv., 2020,10, 29475-29492

Design, synthesis and in silico studies of new quinazolinone derivatives as antitumor PARP-1 inhibitors

S. K. Ramadan, E. Z. Elrazaz, K. A. M. Abouzid and A. M. El-Naggar, RSC Adv., 2020, 10, 29475 DOI: 10.1039/D0RA05943A

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