Synthesis and antifungal activities of novel 1,3-beta-D-glucan synthase inhibitors. Part 1.
Highly potent 1,3-beta-D-glucan synthase inhibitors 10, 11 and 13 have been identified by the chemical modification of the fungicidal macrocyclic lipopeptidolactone, RO-09-3655 (1), isolated from the cultured broth of Deuteromycotinia spp. D-Ornithine derivative (10) showed improved antifungal activity in the systemic candidiasis model in mice and reduced hepatotoxicity in vitro, as compared with 1.
Masubuchi
K
K
Department of Chemistry, Nippon Roche Research Center, Kanagawa, Japan.
Okada
T
T
Kohchi
M
M
Sakaitani
M
M
Mizuguchi
E
E
Shirai
H
H
Aoki
M
M
Watanabe
T
T
Kondoh
O
O
Yamazaki
T
T
Satoh
Y
Y
Kobayashi
K
K
Inoue
T
T
Horii
I
I
Shimma
N
N
D000818:Animals; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D000935:Antifungal Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D002176:Candida albicans / Q000187:drug effects; D002177:Candidiasis / Q000150:complications / Q000188:drug therapy; D020650:Combinatorial Chemistry Techniques; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D005964:Glucosyltransferases / Q000037:antagonists & inhibitors*; D002479:Inclusion Bodies / Q000187:drug effects / Q000382:microbiology; D020128:Inhibitory Concentration 50; D007783:Lactones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D008099:Liver / Q000187:drug effects / Q000382:microbiology / Q000473:pathology; D008565:Membrane Proteins; D051379:Mice; D008826:Microbial Sensitivity Tests; D010455:Peptides; D029702:Schizosaccharomyces pombe Proteins; D013329:Structure-Activity Relationship; D015996:Survival Rate; D013810:Therapeutic Equivalency
D000900:Anti-Bacterial Agents; D000935:Antifungal Agents; D004791:Enzyme Inhibitors; D007783:Lactones; D008565:Membrane Proteins; D010455:Peptides; D029702:Schizosaccharomyces pombe Proteins; D005964:Glucosyltransferases; C020570:1,3-beta-glucan synthase