番荔枝内酯类化合物对肝细胞耗氧呼吸的抑制作用及其构效关系

番荔枝内酯类化合物 (ａｎｎｏｎａｃｅｏｕｓａｃｅｔｏｇｅｎｉｎｓ ,ＡＣＧ)是从番荔枝科植物中分离到的末端含γ 内酯环并有生物活性的天然产物 ,目前已经从 4 1个属15 0种番荔枝科植物中获得 30 0多个ＡＣＧ化合物[1～ 3 ] 。由于其有较大的应用前景 ,对ＡＣＧ化合物的分离鉴定及生物活性检测已成为天然产物研究中非常活跃的内容。ＡＣＧ的主要结构特征是一条碳原子数为 35或37的烷基链 ,末端含甲基取代的内酯环 (有时经重排为内缩酮 ) ,链上带有 0～ 3个四氢呋喃环(ｔｅｔｒａｈｙｄｒｏｆｕｒａｎ ,ＴＨＦ) ,和一定数目的含氧官能团(…

INHIBITION OF OXYGEN CONSUMPTION BY ANNONACEOUS ACETOGENINS IN LIVER CELL RESPIRATION AND THEIR STRUCTURE-ACTIVITY RELATIONSHIP

AIM: To study the inhibition of oxygen consumption by annonaceous acetogenins (ACG) and their structure-activity relationship (SAR). METHODS: The inhibition of oxygen consumption in chicken liver cell respiration by different structural ACG was studied by using oxygen electrode technique. RESULTS: Six ACG showed potent inhibitory effects like rotenone which was a classical inhibitor of mitochondrial complex I, and was more potent than complex IV inhibitor KCN. The IC50 values of six ACG for inhibiting oxygen consumption suggested that bistetrahydrofuran (THF) ACG was 7-11 times more active than non-THF ACG, and A1-type ACG was more potent than A2-type ACG. CONCLUSION: The terminal gamma-lactone was crucial for the inhibition of oxygen consumption. The distance between THF and gamma-lactone, the hydroxyl groups in the alkyl chain, were the important factors of SAR, but the 4-OH group possibly played some negative role in the exhibit of potent activity.