Synthesis,Anticancer Activity,Structure-Activity Relationship and Mechanistic Investigations of Falcarindiol Analogues |
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| Authors: | Wan-Li Tan Dr Chun Zhang Yang Li Dr Kai Guo Dr Xiao-Wei Gao Dr Jun Wei Dr Dong Yi Prof Lin Pu Prof?Dr Qin Wang |
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| Affiliation: | 1. Department of Medicinal Chemistry, School of Pharmacy, Southwest Medical University, Luzhou, 646000 China
These authors contributed equally to this work.;2. Department of Medicinal Chemistry, School of Pharmacy, Southwest Medical University, Luzhou, 646000 China;3. Department of Chemistry, University of Virginia, Charlottesville, VA 22904-4319 USA |
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| Abstract: | Forty samples of optically active falcarindiol analogues are synthesized by using the easily available C2 symmetric (R)- and (S)-1,1’-binaphth-2-ol (BINOL) in combination with Ti(OiPr)4, Zn powder and EtI. Their anticancer activities on Hccc-9810, HepG2, MDA-MB-231, Hela, MG-63 and H460 cells are assayed to elucidate their structure-activity relationships. These results showed that the falcarindiol analogue (3R,8S)- 2 i with the terminal double bond has the most potent anti-proliferation effect on Hccc-9810 cells with IC50 value of 0.46 μM. The falcarindiol analogue (3R,8S)- 2 i can induce obvious Hccc-9810 cell apoptosis in a concentration-dependent manner by Hoechst staining and flow cytometry analysis. The proposed mechanism suggests that the falcarindiol analogue (3R,8S)- 2 i increases LDH release and MDA content, and reduces the levels of SOD activity, which lead to the accumulation of oxidative stress and induce apoptosis in Hccc-9810 cells. |
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| Keywords: | asymmetric synthesis 1 1′-binaphth-2-ol (BINOL) falcarindiol analogues anticancer activities structure-activity relationships mechanism |
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