New antifungal antibiotics pradimicins FA-1 and FA-2: D-serine analogs of pradimicins A and C.
Pradimicin FA-1 was produced via directed biosynthesis with substitution of D-serine for D-alanine in the 15-position of pradimicin A. This substitution was achieved by the addition of D-serine to the culture medium of Actinomadura hibisca P157-2. Likewise, pradimicin FA-2 was co-produced along with pradimicin FA-1 when the pradimicins A and C producing strain, A. hibisca A2493 was grown in D-serine-supplemented medium. The new pradimicin analogs share a common core structure of 5,6-dihydrobenzo[a]naphthacenequinone substituted by D-serine at C-15, but differ in the disaccharide moiety at C-5. Pradimicin FA-1 has an N-methylamino sugar and D-xylose. Pradimicin FA-2 is the des-N-methyl analog of pradimicin FA-1. The in vitro and in vivo antifungal activity of the analogs was comparable to that of pradimicin A.
Sawada
Y
Y
Bristol-Myers Research Institute, Ltd., Tokyo Research Center, Japan.
Hatori
M
M
Yamamoto
H
H
Nishio
M
M
Miyaki
T
T
Oki
T
T
D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D018943:Anthracyclines; D000903:Antibiotics, Antineoplastic / Q000096:biosynthesis* / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D000935:Antifungal Agents / Q000096:biosynthesis* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D002177:Candidiasis / Q000188:drug therapy; D002851:Chromatography, High Pressure Liquid; D002855:Chromatography, Thin Layer; D005285:Fermentation; D005658:Fungi / Q000187:drug effects*; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D008813:Mice, Inbred ICR; D015394:Molecular Structure; D009618:Nocardiaceae / Q000378:metabolism*; D000095643:Pradimicins and Benanomicins
D000596:Amino Acids; D018943:Anthracyclines; D000903:Antibiotics, Antineoplastic; D000935:Antifungal Agents; C056806:benanomicin B; D000095643:Pradimicins and Benanomicins; C058036:pradimicin A; C066543:pradimicin FA 1; C066544:pradimicin FA 2