Funabashi Y, Horiguchi T, Iinuma S, Tanida S, Harada S
Discovery Research Laboratories II, Takeda Chemical Industries, Ltd., Osaka, Japan.
J Antibiot (Tokyo). 1994 Nov;47(11):1202-18. doi: 10.7164/antibiotics.47.1202.
Fungal metabolites with an epi-oligothiadiketopiperazine structure, TAN-1496 A, C and E, were isolated from the culture broth of Microsphaeropsis sp. FL-16144. Their molecular formulas were determined to be C22H28N2O9S2, C22H28N2O9S3 and C22H28N2O9S4, respectively. Structures were determined by comparing the NMR data with those of known diketopiperazine antibiotics, sirodesmins. These metabolites inhibited the relaxation of supercoiled pBR322 DNA by calf thymus topoisomerase I but did not affect the decatenation of kinetoplast DNA by calf thymus topoisomerase II at concentration up to 500 microM. They strongly suppressed the growth of various murine and human tumor cells and induced apoptosis. Moreover, various derivatives were synthesized to investigate the relationship of their functional groups and biological activities.
从球座菌属（Microsphaeropsis sp.）FL-16144的培养液中分离出具有表-寡硫代二酮哌嗪结构的真菌代谢产物TAN-1496 A、C和E。它们的分子式分别确定为C22H28N2O9S2、C22H28N2O9S3和C22H28N2O9S4。通过将核磁共振数据与已知的二酮哌嗪抗生素西罗地辛的核磁共振数据进行比较来确定其结构。这些代谢产物在浓度高达500微摩尔时可抑制小牛胸腺拓扑异构酶I介导的超螺旋pBR322 DNA的松弛，但不影响小牛胸腺拓扑异构酶II介导的动质体DNA的解连环。它们强烈抑制各种鼠类和人类肿瘤细胞的生长并诱导细胞凋亡。此外，还合成了各种衍生物以研究其官能团与生物活性之间的关系。
