Unprecedented sesquiterpene-polycyclic polyprenylated acylphloroglucinol adduct against acute myeloid leukemia via inhibiting mitochondrial complex Ⅴ  

作　　者：Zhengyi Shi Jie Yin Yang Xiao Zhangrong Hou Fei Song Jianping Wang Qingyi Tong Changxing Qi Yonghui Zhang 

机构地区：[1]Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation,School of Pharmacy,Tongji Medical College,Huazhong University of Science andTechnology,Wuhan430030,China

出　　处：《Chinese Chemical Letters》2024年第10期305-308,共4页中国化学快报（英文版）

基　　金：supported financially by the National Natural Science Foundation for Distinguished Young Scholars(No.81725021);the National Natural Science Foundation of China(Nos.82003633 and 82104043);the National Natural Science Foundation of Hubei Province(No.2023AFB791)。

摘　　要：Monosescinol A(1),the first example of sesquiterpene–polycyclic polyprenylated acylphloroglucinol(PPAP)adduct,which represented a new subclass of PPAP-type natural products,along with two new congeners with normal spiro 6/6/5 tricyclic architecture,were isolated from Hypericum longistylum.Monosescinol A possessed an unprecedented 6/5/5/6/6 pentacyclic carbon skeleton that might be assembled from the 6/6/5 carbon skeleton,via the splitting decomposition of C-3/C-14,and the attack from the C-3 in the PPAP core to C-28 in sesquiterpene section.In addition,we have firstly confirmed that 24R configuration was existed in sec–Bu containing PPAPs by single crystal diffraction data analysis of monosescinol B(2),that might provide an enlightenment in the configurational determination of sec–Bu containing PPAPs.Significantly,further pharmacological research has found that compound 1 exhibited remarkable pharmacological effects against acute myeloid leukemia(AML)cell lines,with direct inhibition of mitochondrial complex V and an increase in mitochondrial membrane potential,and led to an induction of oxidative stress,endogenous inflammation,and apoptosis of AML cells.

关 键 词：PPAP adduct Single-crystal X-ray diffraction Keto-enol tautomerism Plausiblebiosynthetic pathway Cytotoxic activity 

分 类 号：O629.61[理学—有机化学] R733.71[理学—化学]