Synthesis and <i>in vitro</i> Anti-proliferative Activities on LNCaP, LS180 and MKN45 of Novel 20(<i>R</i>)-Panaxadiol Derivatives

Author(s):

Jianqiang Deng, Xinyu Yang, Mingzhu Luan, Shuqi Liu, Juan Zhang, Sheng Jiang, Wenshui Wang, Guige Hou, Qingguo Meng* and Hongbo Wang*   Pages 1731 - 1739 ( 9 )

Abstract:

<p>Background: 20(<i>R</i>)-PD, a tetracyclic triterpenoid, is a non-natural saponin present in the form of protopanaxadiol. Because of its essential biological activities, especially anti-tumor activity, structural modification of 20(<i>R</i>)-PD and the development of innovative and novel 20(<i>R</i>)-PD derivatives with better anti-tumor activity are increasingly relevant. </p><p> Aims: 20(<i>R</i>)-Panaxadiol (20(<i>R</i>)-PD) can inhibit tumor proliferation. Three series of novel 20(<i>R</i>)-PD derivatives were synthesized by modifying the A-ring. </p><p> Objective: The objective of this work was to synthesize and evaluate the <i>in vitro</i> anti-proliferative activities of 20(<i>R</i>)- PD derivatives in LNCaP, LS180, and MKN45 cancer cells. Structural modifications were performed at the C-3 position and A-ring. </p><p> Methods: The <i>in vitro</i> anti-proliferative activities of novel derivatives in LNCaP, LS180, and MKN45 cells were evaluated by the MTT assay. The effects of compounds 5 and C9 on apoptosis were determined by flow cytometry. </p><p> Results: Compounds 5, B2, C2, C4, C7, C8, C9, C10, and C11 exhibited good anti-proliferative activities in LNCaP, LS180, and MKN45 cells <i>in vitro</i>. The best anti-proliferative activity was observed for the C-series derivatives with the introduction of amino acids at the C-3 position. C9 exhibited good potent activity with an IC₅₀ of 2.89 μM. </p><p> Conclusion: Compound C9 is a potential candidate with potent anti-proliferative activity.</p>

Keywords:

Ginseng, 20(<i>R</i>)-panaxadiol, derivatives, synthesis, anti-proliferative activity, apoptosis.

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