Synthesis of novel 25-hydroxyprotopanaxadiol derivatives by methylation and methoxycarbonylation using dimethyl carbonate as a environment-friendly reagent and their anti-tumor evaluation

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• 作者：Junhui Guo ; Zhe Xu ; Yafei Liu ; Xude Wang ; Yuqing Zhao ; ^{zyq4885@126.com" class="auth_mail" title="E-mail the corresponding author}
• 关键词：25-Hydroxyprotopanaxadiol ; Dimethyl carbonate ; Derivatives ; Anti-tumor activity
• 刊名：Bioorganic & Medicinal Chemistry Letters
• 出版年：2016
• 出版时间：1 October 2016
• 年：2016
• 卷：26
• 期：19
• 页码：4763-4768
• 全文大小：730 K

文摘

A previous study involving 25-hydroxyprotopanaxadiol (25-OH-PPD) illustrated that the anti-cancer activity increased by 1–3 times after C-3/C-12-OH was substituted by short-chain fatty acids. In addition, 25-OCH₃-PPD was also one of our research interests; the unique difference in structure between 25-OH-PPD and 25-OCH₃-PPD is that in C-25, the latter activity was 2–5 times higher than that of 25-OH-PPD. These data serves as the scientific basis of our continuing research. To further confirm the effect of short chain acylated and methylated products on the activity and to identify more potent, higher selectivity compounds, we modified 25-OH-PPD with a green environment-friendly and non-toxic chemical dimethyl carbonate (DMC), which plays the role of both solvent and reagent. This experiment yielded 14 derivatives. Their in vitro anti-tumor activities were tested on two different human tumor cell lines (HeLa and DU145) and one normal cell line (IOSE144) by standard MTT assay. The results showed that compounds 3, 5, 6, 10, 11, 12, and 13 exhibited higher cytotoxic activity on two cell lines, with IC₅₀ values within the range of 1.1–12 μM. Compounds 12 and 13 exhibited the highest potent activity, with IC₅₀ values of 1.1 and 1.2 μM, respectively, on HeLa cells. Antitumor activity significantly increased after the hydroxyl groups are substituted by methyl. The results of the present study may provide useful data for evaluating the structure–activity relationships of other dammarane-type sapogenins and developing new antitumor agents.