Structure activity relationship of annonaceous acetogenins against multidrug resistant human lung cancer cell line A549/Taxol in vitro

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.