{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"volume":["10(49)"],"submitter":["Ramadan SK"],"pubmed_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 IC<sub>50</sub> = 30.38 nM comparable to Olaparib, which has IC<sub>50</sub> = 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 <i>in silico</i> 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."],"journal":["RSC advances"],"pagination":["29475-29492"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC9055986"],"repository":["biostudies-literature"],"pubmed_title":["Design, synthesis and <i>in silico</i> studies of new quinazolinone derivatives as antitumor PARP-1 inhibitors."],"pmcid":["PMC9055986"],"pubmed_authors":["Elrazaz EZ","El-Naggar AM","Ramadan SK","Abouzid KAM"],"additional_accession":[]},"is_claimable":false,"name":"Design, synthesis and <i>in silico</i> studies of new quinazolinone derivatives as antitumor PARP-1 inhibitors.","description":"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 IC<sub>50</sub> = 30.38 nM comparable to Olaparib, which has IC<sub>50</sub> = 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 <i>in silico</i> 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.","dates":{"release":"2020-01-01T00:00:00Z","publication":"2020 Aug","modification":"2026-05-30T20:53:36.512Z","creation":"2025-04-04T10:02:18.454Z"},"accession":"S-EPMC9055986","cross_references":{"pubmed":["35521104"],"doi":["10.1039/d0ra05943a"]}}