School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
Bioorg Chem. 2023 Apr;133:106389. doi: 10.1016/j.bioorg.2023.106389. Epub 2023 Jan 24.
Garcinol is a polyisoprenylated benzophenone isolated from Garcinia. It has been reported to have a variety of intriguing biological effects, including anticancer, anti-inflammatory, and antioxidant capabilities. The purpose of this research is to thoroughly evaluate garcinol and a series of its analogues in terms of synthesis, structural diversity, biosynthesis, and potential for preventing carcinoma cell proliferation. Garcinopicrobenzophenone and eugeniaphenone, which contain a unique cyclobutyl unit at C-5, were initially synthesized using the procedures utilized in the synthesis of garcinol. All the natural analogs of garcinol were produced at completion of the synthesis, and their structures and absolute configurations were clarified. Based on the synthesis, a possible biogenetic synthesis pathway towards cambogin, 13,14-didehydroxyisogarcinol via O-cyclization, and garcinopicrobenzophenone or eugeniaphenone via C-cyclization was proposed. The cytotoxicity of polyisoprenylated benzophenones produced in our group was tested, and the structure-activity relationship was summarized. The mechanism by which garcinol, cambogin, and 21' induce apoptosis was studied. Cambogin and 21' were shown to have a greater capacity to cause apoptosis in pancreatic cancer BXPC3 cells, and the suppression of BXPC3 cells by 21' might be attributed to the target of STAT3 signaling. Garcinol could cause pyroptosis and apoptosis in pancreatic cancer cells at the same time, which was the first time that garcinol was identified as a possible chemotherapeutic agent that could significantly promote pyroptosis in cancer cells.
藤黄酚是从藤黄中分离得到的一种多异戊烯基二苯甲酮。它已被报道具有多种有趣的生物学效应，包括抗癌、抗炎和抗氧化能力。本研究旨在全面评估藤黄酚及其一系列类似物在合成、结构多样性、生物合成以及预防癌细胞增殖方面的潜力。藤黄酚和 Eugeniphenone 最初是使用合成藤黄酚的方法合成的，它们在 C-5 位含有独特的环丁基单元。所有天然藤黄酚类似物在合成完成后都产生了，并对其结构和绝对构型进行了阐明。基于合成，提出了一个可能的生物合成途径，通过 O-环化生成 Cambogin 和 13,14-二去羟基异藤黄酚，通过 C-环化生成藤黄酚。测试了本课题组合成的多异戊烯基二苯甲酮的细胞毒性，并总结了结构-活性关系。研究了藤黄酚、Cambogin 和 21'诱导细胞凋亡的机制。Cambogin 和 21'在胰腺癌细胞 BXPC3 中具有更强的诱导细胞凋亡的能力，而 21'对 BXPC3 细胞的抑制作用可能归因于 STAT3 信号的靶标。藤黄酚可以同时在胰腺癌细胞中引起细胞焦亡和细胞凋亡，这是首次发现藤黄酚可能是一种能够显著促进癌细胞细胞焦亡的化疗药物。
