Publication: Investigation of aromatase inhibitory activity of metal complexes of 8-hydroxyquinoline and uracil derivatives
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Issued Date
2014-08-14
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eng
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Drug Design, Development and Therapy
Bibliographic Citation
Drug Design, Development and Therapy. Vol.8, 2014, 1089-1096
Suggested Citation
Veda Prachayasittikul, Ratchanok Pingaew, Virapong Prachayasittikul, Chanin Nantasenamat, Somsak Ruchirawat, Supaluk Prachayasittikul Investigation of aromatase inhibitory activity of metal complexes of 8-hydroxyquinoline and uracil derivatives. Drug Design, Development and Therapy. Vol.8, 2014, 1089-1096. Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/2077
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Title
Investigation of aromatase inhibitory activity of metal complexes of 8-hydroxyquinoline and uracil derivatives
Abstract
Purpose: 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 IC50 0.30 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 IC50 range 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.