岩白菜素: 一种通用易得的生物活性修饰前体

doi:10.5246/jcps.2023.05.029

摘要/Abstract

摘要：

岩白菜素是中药岩白菜的主要生物活性成分和许多植物家族的重要成分或次级代谢产物, 岩白菜素及其衍生物因其独特的生物活性和药理性质引起了人们的极大兴趣。在过去的几十年中, 大量岩白菜素衍生物合成出来并考察其生物活性, 取得了许多积极的结果。这些研究有助于从岩白菜素衍生物中发现和鉴定新的候选药物治疗剂, 了解它们的分子靶点和药理作用机制。本工作总结了岩白菜素半合成衍生物的零散信息及在生物活性修饰方面的最新进展。

关键词: 岩白菜素, 岩白菜素衍生物, 天然活性成分, 多功能前体, 结构修饰

Abstract:

Bergenin, as a major bioactive ingredient of traditional Chinese medicine bergenia, can be found to be a significant component or a secondary metabolite in many families. Bergenin and its derivatives have aroused great interest because their unique bioactivities and pharmacological properties have been gradually disclosed over the past decades. A great number of bergenin derivatives have been synthesized, and their biological activities have been surveyed to achieve many satisfactory results in recent several years. These studies are beneficial in discovering and identifying novel candidates from bergenin derivatives as potential therapeutic drugs and help us understand their molecular targets and mechanisms of pharmacological action. This present work compiled scattered information on semisynthetic derivatives of bergenin and highlighted their recent advances in bioactive modifications.

Key words: Bergenin, Bergenin derivatives, Natural active ingredients, Versatile precursors, Structural modifications

Supporting:

蔡粟茜, 张可锋, 蔡小华. 岩白菜素: 一种通用易得的生物活性修饰前体[J]. 中国药学(英文版), 2023, 32(5): 333-350.

Suqian Cai, Kefeng Zhang, Xiaohua Cai. Bergenin: a versatile and readily available precursor for bioactive modifications[J]. Journal of Chinese Pharmaceutical Sciences, 2023, 32(5): 333-350.

图/表 19

Scheme 1. Chemical structure and characteristics of bergenin.

Scheme 2. Synthesis of tri-O-methylnorbergenin via the pathway of aryl-α-C-glucosidation.

Scheme 3. Synthesis of bergenin via the cross-coupling of saccharide-based alkenyl boronic acids with aryl halides.

Scheme 4. Bergenin derivatives for anti-inflammatory activities.

Table 1. Bergenin derivatives as inflammatory mediators NO and TNF-α.

Scheme 5. Bergenin derivatives for their cytotoxicity against Artemia salina.

Scheme 6. Substituted compounds at the eighth position with anti-platelet aggregation activity.

Scheme 7. Bergenin-triazole hybrids and their potentials against A-549 and HeLa cell lines.

Table 2. IC50 values for compounds against DU-145, A549, HCT 116, HepG2, and HeLa cell lines.

Scheme 8. Bergenin derivatives for their cytotoxicity against Hela cell lines.

Scheme 9. Bergenin derivatives and their immunosuppressive activities.

Scheme 10. Bergenin derivatives for their anti-inflammatory and anti-narcotic effects.

Scheme 11. Cytotoxic activity of bergenin derivatives against DU-145 and BGC-823 cells.

Scheme 12. Antioxidative activities for esterification derivatives of bergenin.

Scheme 13. Esterification derivatives of bergenin for antitumor activities against PC-3, A549, SGC-7901, MCF-7, and HepG2 cell lines.

Table 3. Antiproliferative activity of compounds against PC-3, SGC-7901, A549, MCF-7, and HepG2 cell lines in vitro.

Scheme 14. Antitrypanosomal activity of semisynthetic bergenin derivatives.

Scheme 15. The activity of bergenin derivatives containing nitrogen moieties against K562 and HL60 cell lines.

Scheme 16. The activity of aza-bergenin derivative against A549 cell line.

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