Production, isolation and structure determination of novel fluoroindolocarbazoles from Saccharothrix aerocolonigenes ATCC 39243.
Saccharothrix aerocolonigenes ATCC 39243 produces an indolocarbazole antitumor agent rebeccamycin under submerged fermentation conditions. Adding DL-6-fluorotryptophan to culture of S. aerocolonigenes ATCC 39243 induces the formation of two novel indolocarbazoles, fluoroindolocarbazoles A and B. Feeding DL-5-fluorotryptophan to culture of S. aerocolonigenes ATCC 39243 induces the production of a novel indolocarbazole, fluoroindolocarbazole C. These fluoroindolocarbazoles have been isolated from culture broth and purified to homogeneity by vacuum liquid chromatography and column chromatography. All three fluoroindolocarbazoles are more potent than rebeccamycin against P388 leukemia by ip route in murine model.
Lam
K S
KS
Bristol-Meyers Squibb Company, Pharmaceutical Research Institute, Wallingford, CT 06492, USA. Kin.Lam@bms.com
Schroeder
D R
DR
Veitch
J M
JM
Colson
K L
KL
Matson
J A
JA
Rose
W C
WC
Doyle
T W
TW
Forenza
S
S
D000192:Actinomycetales / Q000737:chemistry / Q000378:metabolism*; D000617:Aminoglycosides; D000818:Animals; D000900:Anti-Bacterial Agents / Q000096:biosynthesis / Q000302:isolation & purification / Q000494:pharmacology; D000903:Antibiotics, Antineoplastic / Q000096:biosynthesis / Q000737:chemistry* / Q000302:isolation & purification* / Q000494:pharmacology; D002227:Carbazoles; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D005260:Female; D007211:Indoles; D007942:Leukemia, Experimental / Q000188:drug therapy; D051379:Mice; D008807:Mice, Inbred BALB C; D008811:Mice, Inbred DBA; D015394:Molecular Structure; D010865:Pilot Projects
D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D000903:Antibiotics, Antineoplastic; D002227:Carbazoles; D007211:Indoles; C423642:fluoroindolocarbazole A; C423643:fluoroindolocarbazole B; C423644:fluoroindolocarbazole C; C053339:rebeccamycin