Novel Macrolide Actin-inhibitors Isolated from Sea Sponges

Several marine toxins with macrolide structure have been found to act on actin. One of these toxins is mycalolide B isolated from the genus Mycale. This compound belongs to macrolide antibiotics and consists of tris-oxazole with strong cytotoxic activity ($IC_{50}$: 10-50 nM for growth of L1210 murine leukemia cells). This compound was found to be an actin-depolymerizing agent with the mode of action distinct from that of the known actin inhibitor, cytochalasin D. Tolytoxin, a macrolide isolated from cyano-bacteria with similar chemical structure to mycalolide B, seems to have similar effect. Another macrolide compound, aplyronine A, showed the effects similar to those of mycalolide B. Although bistheonellide A, a dimeric macrolide, did not show a severing effect, it de polymerized F-actin and sequestered G-actin by forming 1 : 2 complex with G-actins. Swinholide A has a structure and effects similar to those of bistheonel-lide A. In conclusion, mycalolide B, tolytoxin, aplyronine A, bistheonellide A and swinholide A are the members of "actin de polymerizing macrolide" the mechanism of which is different from that of cytochalasin D.halasin D.