TAN-1323-C AND TAN-1323-D, NEW CONCANAMYCIN-GROUP ANTIBIOTICS - DETECTION OF THE ANGIOSTATIC ACTIVITY WITH A WIDE-RANGE OF MACROLIDE ANTIBIOTICS

We detected potent angiostatic activity in a MeOH extract from the myc elia of microbial strain S-45628 in the chick chorioallantoic membrane (CAM) assay. The producer was taxonomically characterized as Streptom yces purpurascens. Active principles designated TAN-1323 A similar to 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 test ed in the CAM assay, components B and D gave huge avascular zones at t he extremely low doses of 10 similar to 100 ng/disk, although componen ts A and C showed far weaker activity due to their preferential tissue -damaging effect on the CAM. The discovery that these 18-membered macr olide antibiotics are angiostatic substances prompted us to examine ot her types of macrolide antibiotics, leading to the discovery that 16-m embered macrolide antibiotics such as bafilomycin C1, tylosin and leuc omycin also show angiostatic activity on the CAM. Thus, angiostatic po tential is widely distributed among macrolide antibiotics. The mechani sm of action of these macrolide antibiotics is also discussed.