Synthesis and antifungal activities of novel 1,3-beta-D-glucan synthase inhibitors. Part 2.
Highly potent 1,3-beta-D-glucan synthase inhibitors, 7b, 10a, 10b and 12, have been identified by the chemical modification of the ornithine residue of a fungicidal macrocyclic lipopeptidolactone, RO-09-3655 (1), isolated from the cultured broth of Deuteromycotinia spp. These compounds showed stronger antifungal activity against systemic candidiasis as well as pulmonary aspergillosis in mice, and less hepatotoxicity as compared with 1.
Masubuchi
K
K
Department of Chemistry, Nippon Roche Research Center, Kamakura, Kanagawra, Japan.
Okada
T
T
Kohchi
M
M
Murata
T
T
Tsukazaki
M
M
Kondoh
O
O
Yamazaki
T
T
Satoh
Y
Y
Ono
Y
Y
Tsukaguchi
T
T
Kobayashi
K
K
Ono
N
N
Inoue
T
T
Horii
I
I
Shimma
N
N
D000818:Animals; D000935:Antifungal Agents / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity; D001229:Aspergillosis, Allergic Bronchopulmonary / Q000150:complications / Q000188:drug therapy; D001232:Aspergillus fumigatus / Q000187:drug effects; D002175:Candida / Q000187:drug effects; D002177:Candidiasis / Q000150:complications / Q000188:drug therapy; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology / Q000633:toxicity; D005964:Glucosyltransferases / Q000037:antagonists & inhibitors*; D016867:Immunocompromised Host / Q000187:drug effects; D002479:Inclusion Bodies / Q000187:drug effects; D007275:Injections, Intravenous; D008565:Membrane Proteins; D051379:Mice; D008826:Microbial Sensitivity Tests; D003904:Mitosporic Fungi / Q000737:chemistry; D010456:Peptides, Cyclic / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity; D029702:Schizosaccharomyces pombe Proteins; D013997:Time Factors
D000935:Antifungal Agents; D004791:Enzyme Inhibitors; D008565:Membrane Proteins; D010456:Peptides, Cyclic; D029702:Schizosaccharomyces pombe Proteins; C444839:lipopeptidolactone; D005964:Glucosyltransferases; C020570:1,3-beta-glucan synthase