Microbial modification of pradimicins at C-11 leading to 11-O-demethyl- and 11-O-L-xylosylpradimicins A and FA-1.
In a screen of pradimicin-nonproducing mutants derived from Actinomadura verrucosospora subsp. neohibisca R103-3, we found a strain capable of producing 11-hydroxyl analogs of pradimicins A and FA-1, designated pradimicins H and FH, respectively. Feeding of pradimicins H and FH to growing cultures of an actinomycete strain AA3798 produced 11-O-L-xylosylpradimicins H and FH, respectively. These 11-O-L-xylosylpradimicins had a broad spectrum of antifungal activity and demonstrated in vivo efficacies against Candida albicans in mice.
Furumai
T
T
Bristol-Myers Squibb Research Institute, Tokyo, Japan.
Yamamoto
H
H
Narita
Y
Y
Hasegawa
T
T
Aburaki
S
S
Kakushima
M
M
Oki
T
T
D000190:Actinomyces / Q000737:chemistry*; D000818:Animals; D018943:Anthracyclines; D000903:Antibiotics, Antineoplastic / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D000935:Antifungal Agents / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D002177:Candidiasis / Q000188:drug therapy; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D008826:Microbial Sensitivity Tests; D013329:Structure-Activity Relationship; D000095643:Pradimicins and Benanomicins
D018943:Anthracyclines; D000903:Antibiotics, Antineoplastic; D000935:Antifungal Agents; C084376:11-O-xylosylpradimicin FH; C084375:11-O-xylosylpradimicin H; C084374:pradimicin FH; D000095643:Pradimicins and Benanomicins; C084373:pradimicin H