Design, synthesis and in silico studies of new quinazolinone derivatives as antitumor PARP-1 inhibitors
Ramadan, Sayed; Elrazaz, Eman; Khaled A M Abouzid; El- naggar, Abeer;
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.
Other data
Title | Design, synthesis and in silico studies of new quinazolinone derivatives as antitumor PARP-1 inhibitors | Authors | Ramadan, Sayed ; Elrazaz, Eman ; Khaled A M Abouzid ; El- naggar, Abeer | Keywords | ANTICANCER; POLYMERASE; QSAR; NANOPARTICLES; CHALCONES; DISCOVERY; APOPTOSIS; STRATEGY; UPDATE; BREAST | Issue Date | 10-Aug-2020 | Publisher | ROYAL SOC CHEMISTRY | Journal | RSC Advances | Volume | 10 | Issue | 49 | Start page | 29475 | End page | 29492 | DOI | 10.1039/d0ra05943a | Scopus ID | 2-s2.0-85090400904 | Web of science ID | WOS:000560694000050 |
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