Antifungal activities of pradimicin derivatives modified at C4'-amino group.
In order to explore potent derivatives of pradimicins (PRMs), modification of their C4'-amino group was carried out. 4'-N-Cyano (1,2), 4'-deamino-4'-nitroguanidino (4), 4'-deamino-4'-ureido (7-9) and 4'-deamino-4'-thioureido (10) derivatives were synthesized by trimethylsilylation of PRMs A and C, followed by condensation with appropriate reagents. 4'-Deamino-4'-guanidino (5) and 4'-deamino-4'-amidino (6) derivatives were synthesized by catalytic hydrogenation of 4 and 2, respectively. 4'-N-Nitroso derivative 3 was prepared by treatment of PRM A with nitrous acid. Among these compounds, the 4'-N-cyano derivative of PRM C (2) exhibited in vitro and in vivo antifungal activities comparable to the parent compounds together with good water-solubility.
Kamachi
H
H
Bristol-Myers Squibb Research Institute, Bristol-Myers Squibb K.K., Tokyo, Japan.
Okuyama
S
S
Hirano
M
M
Masuyoshi
S
S
Konishi
M
M
Oki
T
T
D000818:Animals; D018943:Anthracyclines; D000903:Antibiotics, Antineoplastic / Q000737:chemistry / Q000494:pharmacology*; D000935:Antifungal Agents / Q000737:chemistry / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D008826:Microbial Sensitivity Tests; D003904:Mitosporic Fungi / Q000187:drug effects*; D012995:Solubility; D013329:Structure-Activity Relationship; D000095643:Pradimicins and Benanomicins
D018943:Anthracyclines; D000903:Antibiotics, Antineoplastic; D000935:Antifungal Agents; C056806:benanomicin B; D000095643:Pradimicins and Benanomicins; C058036:pradimicin A