Indoxamycins A-F. Cytotoxic tricycklic polypropionates from a marine-derived actinomycete.
Six antitumor antibiotics of a new structure class, indoxamycins A-F (1-6), were isolated from a saline culture group of marine-derived actinomyces whose strains showed approximately 96% sequence homology of 16S rDNA with the family streptomycetaceae. The structures of these indoxamycins, which are unusual polyketides composed of six consecutive chiral centers, were assigned by combined spectral and chemical methods. In feeding experiments using a stable isotope label, indoxamycin A was assembled from propionate units initially forming the "aglycon" pentamethyl indeno furan. The discovery of these unprecedented compounds from marine-derived actinomycetes, a low gene homology genus, offers a significant opportunity for drug discovery.
Sato
Seizo
S
Central Research Laboratory, Nippon Suisan Kaisha, Ltd., 559-6 Kitano-machi Hachioji, Tokyo 192-0906, Japan. s-satou@nissui.co.jp
Iwata
Fumie
F
Mukai
Takako
T
Yamada
Shoichi
S
Takeo
Jiro
J
Abe
Akihisa
A
Kawahara
Hiroyuki
H
D039903:Actinobacteria / Q000737:chemistry*; D000903:Antibiotics, Antineoplastic / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D055808:Drug Discovery; D004354:Drug Screening Assays, Antitumor; D006575:Heterocyclic Compounds, 3-Ring / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D006801:Humans; D008386:Marine Biology; D008968:Molecular Conformation; D010316:Particle Size; D011422:Propionates / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D013237:Stereoisomerism
D000903:Antibiotics, Antineoplastic; D006575:Heterocyclic Compounds, 3-Ring; C545164:Indoxamycin A; C545165:Indoxamycin B; C545167:Indoxamycin C; C545168:Indoxamycin D; D011422:Propionates