Structure-activity relationship studies on niphimycin, a guanidylpolyol macrolide antibiotic. Part 1: The role of the N-methyl-N''-alkylguanidinium moiety.
Several N-methyl-N''-alkylguanidinium derivatives were synthesized and used as simplified analogues of niphimycin (NM), a guanidylpolyol macrolide, in structure-activity relationship studies. The C16-alkylated derivative exerted fungicidal activity by directly damaging the fungal plasma membrane and inducing oxidative stress in a manner similar to niphimycin. These results indicate that the N-methyl-N''-alkylguanidinium moiety is required for antifungal activity by NM.
Usuki
Yoshinosuke
Y
Department of Material Science, Graduate School of Science, Osaka City University, 3-3-138 Sugimoto, Sumiyoshi-ku, Osaka 558-8585, Japan. usuki@sci.osaka-cu.ac.jp
Matsumoto
Keiji
K
Inoue
Takatsugu
T
Yoshioka
Koichi
K
Iio
Hideo
H
Tanaka
Toshio
T
D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology*; D000935:Antifungal Agents / Q000737:chemistry / Q000494:pharmacology*; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D005658:Fungi / Q000187:drug effects / Q000254:growth & development; D006094:Gram-Positive Bacteria / Q000187:drug effects / Q000254:growth & development; D006146:Guanidines / Q000737:chemistry / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D018384:Oxidative Stress / Q000187:drug effects; D010713:Phosphatidylcholines / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000254:growth & development; D013329:Structure-Activity Relationship
D000900:Anti-Bacterial Agents; D000935:Antifungal Agents; D006146:Guanidines; D010713:Phosphatidylcholines; D017382:Reactive Oxygen Species; C010492:niphimycin