ABSTRACT
10 kinds of annonaceous acetogenins were selected for antitumor activity testing against human lung cancer cell line A549/Taxol and the structure activity relationship was analyzed.MTT assay was used to detect the inhibitory activities of 10 kinds of annonaceous acetogenins and positive drugs against A549/Taxol cells, respectively uvariamicin-Ⅲ(1), uvariamicin-Ⅱ(2), annosquacin D(3), desacetyluvaricin(4), annosquatin A(5), squamostatin D(6), bullatacin(7), squamocin(8), motrilin(9), annosquatin B(10), verapamil and cisplatin. Annonaceous acetogenins showed significant inhibitory activities against A549/Taxol cells, and were more potent than the positive drug verapamil and cisplatin.The more carbon atoms between the tetrahydrofuran ring and the lactone ring of annonaceous acetogenins exhibited more potency.Besides,ACGs with two substituted hydroxyl showed more potency than the compounds with three substituted hydroxyl in the bis-adjacent-THF ACGs. Furthermore, ACGs with three substituted hydroxyl showed more potency than the compounds with four substituted hydroxyl among the no bis-adjacent-THF ACGs.
ABSTRACT
Objective: To investigate the activity of mono-tetrahydrofuran (THF) annonaceous acetogenins (ACGs) against mitochondrial complex I of rats. Methods: The inhibitory activity of mono-THF ACGs with six different chemical structures against mitochondrial complex I of rats was investigated to clarify the carbon number and substituted hydroxyl number between THF ring and lactone ring as well as the effect of the core configuration in THF ring on mitochondrial complex I of rats. Results: The results show that mono-THF ACGs can inhibit the mitochondrial complex I of rats. With analysis of the results from the structure-activity relationship between antitumoral activity and their chemical structure of mono-THF ACGs, the less the carbon number between the two rings is, the better their inhibitory activities are; The number of substituted hydroxyl groups is not the decisive factor for influencing its activity in mono-THF ACGs. Conclusion: The inhibitory activity of compound's configurations with th/t/er is better than that of the compound's configurations with th/t/th in mono-THF ACGs.