Veda PrachayasittikulRatchanok PingaewChanin NantasenamatSupaluk PrachayasittikulSomsak RuchirawatVirapong PrachayasittikulMahidol UniversitySrinakharinwirot UniversityChulabhorn Research InstituteChulabhorn Graduate Institute2018-11-092018-11-092014-08-14Drug Design, Development and Therapy. Vol.8, (2014), 1089-1096117788812-s2.0-84906242390https://repository.li.mahidol.ac.th/handle/20.500.14594/34216Purpose: Estrogens play important roles in the pathogenesis and progression of breast cancer as well as estrogen-related diseases. Aromatase is a key enzyme in the rate-limiting step of estrogen production, in which its inhibition is one strategy for controlling estrogen levels to improve prognosis of estrogen-related cancers and diseases. Herein, a series of metal (Mn, Cu, and Ni) complexes of 8-hydroxyquinoline (8HQ) and uracil derivatives (4-9) were investigated for their aromatase inhibitory and cytotoxic activities. Methods: The aromatase inhibition assay was performed according to a Gentest™ kit using CYP19 enzyme, wherein ketoconazole and letrozole were used as reference drugs. The cytotoxicity was tested on normal embryonic lung cells (MRC-5) using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Results: Only Cu complexes (6 and 9) exhibited aromatase inhibitory effect with IC500.30 and 1.7 μM, respectively. Cytotoxicity test against MRC-5 cells showed that Mn and Cu complexes (5 and 6), as well as free ligand 8HQ, exhibited activity with IC50range 0.74-6.27 μM. Conclusion: Cu complexes (6 and 9) were found to act as a novel class of aromatase inhibitor. Our findings suggest that these 8HQ-Cu-uracil complexes are promising agents that could be potentially developed as a selective anticancer agent for breast cancer and other estrogen-related diseases. © 2014 Prachayasittikul et al.Mahidol UniversityMedicinePharmacology, Toxicology and PharmaceuticsArticleSCOPUS10.2147/DDDT.S67300