Title:Copper Complexes of 8-Aminoquinoline and Uracils as Novel Aromatase Inhibitors
VOLUME: 14 ISSUE: 8
Author(s):Nujarin Sinthupoom, Veda Prachayasittikul, Ratchanok Pingaew, Apilak Worachartcheewan, Supaluk Prachayasittikul*, Somsak Ruchirawat and Virapong Prachayasittikul*
Affiliation:Department of Clinical Microbiology and Applied Technology, Faculty of Medical Technology, Mahidol University, Bangkok, Center of Data Mining and Biomedical Informatics, Faculty of Medical Technology, Mahidol University, Bangkok, Department of Chemistry, Faculty of Science, Srinakharinwirot University, Bangkok, Department of Community Medical Technology, Faculty of Medical Technology, Mahidol University, Bangkok, Center of Data Mining and Biomedical Informatics, Faculty of Medical Technology, Mahidol University, Bangkok 10700, Center of Excellence on Environmental Health and Toxicology, Commission on Higher Education (CHE), Ministry of Education, Bangkok, Department of Clinical Microbiology and Applied Technology, Faculty of Medical Technology, Mahidol University, Bangkok 10700
Keywords:8-Aminoquinoline, uracil, metal complex, aromatase inhibitor, cytotoxicity, cancer treatment.
Abstract:Background: Currently, aromatase inhibitors (AIs) have been developed for the treatment
of breast cancers and other estrogen-related conditions. However, searching for more and new classes
of AIs is being investigated. 8-Aminoquinoline (8AQ) is an interesting scaffold to be explored. In
particular, 8AQ as its mixed ligands (5-nitrouracil, 5Nu and 5-iodouracil, 5Iu) metal complexes are
potential compounds to be studied.
Objective: Metal complexes of 8AQ-5Nu/5Iu were investigated for aromatase inhibitory activity and
cytotoxicity.
Methods: Metal complexes (1-6) and free ligands were evaluated for aromatase inhibitory and
cytotoxic activities. Aromatase inhibitory activity of the metal complexes was performed according
to a guideline of BD Gentest™ kit using CYP19 enzyme and O-benzyl fluorescein (DBF) as a
substrate. Cytotoxic effect of the compounds was tested against normal embryonic lung cell line
(MRC) using the MTT assay.
Results: Significantly, copper complexes 3 (IC50 = 0.7 μM) and 6 (IC50 = 1.7 μM) were shown to be
active aromatase inhibitors with selectivity indices of 24.74 and16.40, respectively.
Conclusion: Copper complexes of 8AQ-5Nu (3) and of 8AQ-5Iu (6) were highlighted as novel
aromatase inhibitors that could be further developed for therapeutic applications.
