Quinazolinone derivatives as inhibitors of homologous recombinase RAD51

Ward, Ambber, Dong, Lilong, Harris, Jonathan M., Khanna, Kum Kum, Al-Ejeh, Fares, Fairlie, David P., Wiegmans, Adrian P. and Liu, Ligong (2017) Quinazolinone derivatives as inhibitors of homologous recombinase RAD51. Bioorganic & Medicinal Chemistry Letters, 27 14: 3096-3100. doi:10.1016/j.bmcl.2017.05.039

Attached Files (Some files may be inaccessible until you login with your UQ eSpace credentials)
Name Description MIMEType Size Downloads
UQ637752_OA.pdf Full text (open access) application/pdf 527.35KB 0

Author Ward, Ambber
Dong, Lilong
Harris, Jonathan M.
Khanna, Kum Kum
Al-Ejeh, Fares
Fairlie, David P.
Wiegmans, Adrian P.
Liu, Ligong
Title Quinazolinone derivatives as inhibitors of homologous recombinase RAD51
Journal name Bioorganic & Medicinal Chemistry Letters   Check publisher's open access policy
ISSN 1464-3405
Publication date 2017-07-15
Year available 2017
Sub-type Article (original research)
DOI 10.1016/j.bmcl.2017.05.039
Open Access Status Not yet assessed
Volume 27
Issue 14
Start page 3096
End page 3100
Total pages 5
Place of publication Kidlington, Oxford, United Kingdom
Publisher Pergamon Press
Language eng
Abstract RAD51 is a vital component of the homologous recombination DNA repair pathway and is overexpressed in drug-resistant cancers, including aggressive triple negative breast cancer (TNBC). A proposed strategy for improving therapeutic outcomes for patients is through small molecule inhibition of RAD51, thereby sensitizing tumor cells to DNA damaging irradiation and/or chemotherapy. Here we report structure-activity relationships for a library of quinazolinone derivatives. A novel RAD51 inhibitor (17) displays up to 15-fold enhanced inhibition of cell growth in a panel of TNBC cell lines compared to compound B02, and approximately 2-fold increased inhibition of irradiation-induced RAD51 foci formation. Additionally, compound 17 significantly inhibits TNBC cell sensitivity to DNA damage, implying a potentially targeted therapy for cancer treatment.
Keyword DNA repair
Homologous recombination
Triple-negative breast cancer
Q-Index Code C1
Q-Index Status Provisional Code
Grant ID 1117017
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: HERDC Pre-Audit
Institute for Molecular Bioscience - Publications
Version Filter Type
Citation counts: Scopus Citation Count Cited 0 times in Scopus Article
Google Scholar Search Google Scholar
Created: Tue, 20 Jun 2017, 00:03:31 EST by System User on behalf of Learning and Research Services (UQ Library)