title: Two new ring-contracted congeners of rhizopodin illustrate significance of the ring moiety of macrolide toxins on the actin disassembly-mediated cytotoxicity.
abstract: Two new cytotoxic dilactones, bisisorhizopodin (1) and isorhizopodin (2), together with known divalent actin depolymerizer rhizopodin (3), were isolated from the culture broth of a myxobacterium Myxococcus stipitatus. Spectroscopic analyses established that 1 and 2 are doubly and singly acyl-migrated isomers of 3, respectively, and comparison of their cytotoxicity revealed gradual decrease in the activity as the size of the ring contracted. Because the side chains of macrolide toxins uniformly block the contact between the actin protomers, the present result demonstrates substantial contribution of structurally diverse rings to the affinity of macrolide toxins for its target protein.
authors.affiliation: Biotechnology Research Center and Department of Biotechnology, Toyama Prefectural University.
authors.forename: Naoya
authors.initials: N
authors.lastname: Oku
authors.forename: Ayaka
authors.initials: A
authors.lastname: Matsumoto
authors.forename: Takayuki
authors.initials: T
authors.lastname: Matsunaga
authors.forename: Yuhki
authors.initials: Y
authors.lastname: Asano
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Kasai
authors.forename: Shouhei
authors.initials: S
authors.lastname: Matoba
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Igarashi
mesh_terms: D000199:Actins / Q000378:metabolism*; D000818:Animals; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D007536:Isomerism; D018942:Macrolides / Q000737:chemistry* / Q000302:isolation & purification / Q000633:toxicity*; D051379:Mice; D015394:Molecular Structure; D016940:Myxococcus / Q000737:chemistry; D010080:Oxazoles / Q000737:chemistry* / Q000633:toxicity*
chemical_list: D000199:Actins; D018942:Macrolides; D010080:Oxazoles; C081739:rhizopodin