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


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
0960-894X
Publication date 2017-07-15
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
Inhibitor
RAD51
Triple-negative breast cancer
Q-Index Code C1

Document type: Journal Article
Sub-type: Article (original research)
Collections: HERDC Pre-Audit
Institute for Molecular Bioscience - Publications
 
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