Water-soluble pradimicin derivatives, synthesis and antifungal evaluation of N,N-dimethyl pradimicins.
Three N,N-dimethyl pradimicins were synthesized by reductive alkylation of pradimicins A, E and FA-2 and evaluated for antifungal activity, water solubility and acute toxicity in mice. They showed in vitro antifungal activity superior to pradimicin A. N,N-Dimethylpradimicins E and FA-2 showed great improvement in water solubility and animal tolerance. N,N-Dimethylpradimicin FA-2 was effective in 3 experimental in vivo fungal infection models.
Oki
T
T
Bristol-Myers Research Institute, Ltd., Tokyo Research Center, Japan.
Kakushima
M
M
Nishio
M
M
Kamei
H
H
Hirano
M
M
Sawada
Y
Y
Konishi
M
M
D000478:Alkylation; 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; D002175:Candida / Q000187:drug effects; D004195:Disease Models, Animal; D004361:Drug Tolerance; D005658:Fungi / Q000187:drug effects; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D015394:Molecular Structure; D009181:Mycoses / Q000188:drug therapy; D010084:Oxidation-Reduction; D012995:Solubility; D000095643:Pradimicins and Benanomicins
D018943:Anthracyclines; D000903:Antibiotics, Antineoplastic; D000935:Antifungal Agents; C056806:benanomicin B; D000095643:Pradimicins and Benanomicins; C058036:pradimicin A; C066654:N,N-dimethylpradimicin E; C066653:N,N-dimethylpradimicin C; C067714:N,N-dimethylpradimicin FA-2; C066544:pradimicin FA 2