| SHORT COMMUNICATION |
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Synthesis and Cytotoxic Activity of Novel Tetrahydrocurcumin Derivatives Bearing Pyrazole Moiety |
| Ahmed Mahal1, Ping Wu1, Zi-Hua Jiang2, Xiaoyi Wei1 |
1 Key Laboratory of Plant Resources Conservation and Sustainable Utilization/Guangdong Provincial Key Laboratory of Applied Botany, South China Botanical Garden, Chinese Academy of Sciences, Xingke Road 723, Tianhe District, Guangzhou 510650, People's Republic of China;
2 Department of Chemistry, Lakehead University, 955 Oliver Road, Thunder Bay, ON P7B 5E1, Canada |
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Abstract Tetrahydrocurcumin (THC) is a major metabolite of curcumin and plays an important role in curcumin-induced biological effects. THC is a promising preventive and chemotherapeutic agent for cancer. A series of new pyrazole derivatives of THC have been synthesized as potent anticancer agents. Direct condensation of THC with various substituted hydrazines leads to new pyrazole derivatives of THC (1-18). The prepared compounds have been evaluated via in vitro MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay for their cell proliferation-inhibitory activity against human lung adenocarcinoma (A549), human cervical carcinoma (HeLa) and human breast carcinoma (MCF-7) cells. Most derivatives show significantly higher anticancer activity against all three tested cancer cell lines than the parent compound THC. Several compounds (7, 8, 12, 13 and 15) display promising anticancer activity against MCF-7 cell line with IC50 values ranging from 5.8 to 9.3 μM. The most active compound (8) is substituted with 4-bromophenyl group at the pyrazole ring and inhibits the growth of all three tested cancer cell lines with an IC50 values of (8.0 μM, A549), (9.8 μM, HeLa) and (5.8 μM, MCF-7). The obtained compounds can be a good starting point for the development of new lead molecules in the fight against cancer.
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| Keywords
Condensation
Tetrahydrocurcumin
Pyrazole
Anticancer agents
Drug discovery
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| Fund:Ahmed Mahal acknowledges the Chinese Academy of Sciences for financial support through the CAS President's International Fellowship Initiative (2016PM032). The authors are grateful to Mr. Yunfei Yuan, South China Botanical Garden, Chinese Academy of Sciences, for his valuable support with regard to NMR experiments. Many thanks to Ms. Aijun Sun from South China Sea Institute of Oceanology, Chinese Academy of Sciences, for HR-ESIMS measurements. This research was financially supported by National Natural Science Foundation of China (NSFC) (Grant No. 81172942). |
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Corresponding Authors:
Ahmed Mahal, Zi-Hua Jiang
E-mail: ahmed.mahal@scbg.ac.cn;zjiang@lakeheadu.ca
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Issue Date: 09 December 2017
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