Ishii T, Hida T, Iinuma S, Muroi M, Nozaki Y
Discovery Research Division, Takeda Chemical Industries, Ltd., Osaka, Japan.
J Antibiot (Tokyo). 1995 Jan;48(1):12-20. doi: 10.7164/antibiotics.48.12.
We detected potent angiostatic activity in a MeOH extract from the mycelia of microbial strain S-45628 in the chick chorioallantoic membrane (CAM) assay. The producer was taxonomically characterized as Streptomyces purpurascens. Active principles designated TAN-1323 A-D were isolated and determined to be 18-membered macrolide antibiotics; components C and D are new members of this group, while components A and B are identical to concanamycins C and A, respectively. When tested in the CAM assay, components B and D gave huge avascular zones at the extremely low doses of 10-100 ng/disk, although components A and C showed far weaker activity due to their preferential tissue-damaging effect on the CAM. The discovery that these 18-membered macrolide antibiotics are angiostatic substances prompted us to examine other types of macrolide antibiotics, leading to the discovery that 16-membered macrolide antibiotics such as bafilomycin C1, tylosin and leucomycin also show angiostatic activity on the CAM. Thus, angiostatic potential is widely distributed among macrolide antibiotics. The mechanism of action of these macrolide antibiotics is also discussed.
在鸡胚绒毛尿囊膜（CAM）试验中，我们检测到微生物菌株S-45628菌丝体的甲醇提取物具有强大的血管生成抑制活性。该产生菌在分类学上被鉴定为紫色链霉菌。分离出了命名为TAN-1323 A-D的活性成分，并确定它们为18元大环内酯类抗生素；成分C和D是该类别的新成员，而成分A和B分别与伴刀豆球蛋白C和A相同。在CAM试验中进行测试时，成分B和D在极低剂量10-100 ng/圆片时产生了巨大的无血管区，尽管成分A和C由于对CAM有优先的组织损伤作用而显示出弱得多的活性。这些18元大环内酯类抗生素是血管生成抑制物质这一发现促使我们研究其他类型的大环内酯类抗生素，从而发现诸如巴弗洛霉素C1、泰乐菌素和柱晶白霉素等16元大环内酯类抗生素在CAM上也显示出血管生成抑制活性。因此，血管生成抑制潜力在大环内酯类抗生素中广泛分布。还讨论了这些大环内酯类抗生素的作用机制。
