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Anti-Cancer Agents in Medicinal Chemistry

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ISSN (Print): 1871-5206
ISSN (Online): 1875-5992

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Research Article

Synthesis and in vitro Anti-proliferative Activities on LNCaP, LS180 and MKN45 of Novel 20(R)-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*

Volume 23, Issue 15, 2023

Published on: 12 May, 2023

Page: [1731 - 1739] Pages: 9

DOI: 10.2174/1871520623666230412095428

Price: $65

Abstract

Background: 20(R)-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(R)-PD and the development of innovative and novel 20(R)-PD derivatives with better anti-tumor activity are increasingly relevant.

Aims: 20(R)-Panaxadiol (20(R)-PD) can inhibit tumor proliferation. Three series of novel 20(R)-PD derivatives were synthesized by modifying the A-ring.

Objective: The objective of this work was to synthesize and evaluate the in vitro anti-proliferative activities of 20(R)- PD derivatives in LNCaP, LS180, and MKN45 cancer cells. Structural modifications were performed at the C-3 position and A-ring.

Methods: The in vitro 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.

Results: Compounds 5, B2, C2, C4, C7, C8, C9, C10, and C11 exhibited good anti-proliferative activities in LNCaP, LS180, and MKN45 cells in vitro. 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.

Conclusion: Compound C9 is a potential candidate with potent anti-proliferative activity.

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Graphical Abstract

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