| RRC ID |
29383
|
| 著者 |
Paudel A, Kaneko K, Watanabe A, Matsunaga S, Kanai M, Hamamoto H, Sekimizu K.
|
| タイトル |
Structure-activity relationship study of novel iminothiadiazolo-pyrimidinone antimicrobial agents.
|
| ジャーナル |
J Antibiot (Tokyo)
|
| Abstract |
An iminothiadiazolo-pyrimidinone derivative, 0002-04-KK, harboring a furan moiety, acts as an antimicrobial agent with a minimum inhibitory concentration (MIC) against Staphylococcus aureus of 25 μg ml(-1). Several derivatives of 0002-04-KK were synthesized and among them 0026-59-KK, harboring a nitrofuran moiety, had the most potent antimicrobial activity with an MIC of 6 μg ml(-1). Both 0002-04-KK and 0026-59-KK inhibited the biosynthesis of DNA, RNA and proteins. Peptidoglycan biosynthesis was inhibited by 0026-59-KK, and slightly inhibited by 0002-04-KK. Derivative 0002-04-KK showed bactericidal activity in contrast to the bacteriostatic activity of 0002-04-KK. Derivative 0002-04-KK had less toxicity in silkworms (lethal dose fifty (LD50): >230 μg g(-1)) than 0002-04-KK (LD50: 100 μg g(-1)). The bactericidal activity against S. aureus was because of the nitrofuran moiety. These findings suggest that iminothiadiazolo-pyrimidinone compounds could be used as lead molecules to develop antimicrobial agents.
|
| 巻・号 |
66(11)
|
| ページ |
663-7
|
| 公開日 |
2013-11-1
|
| DOI |
10.1038/ja.2013.69
|
| PII |
ja201369
|
| PMID |
23820613
|
| MeSH |
Animals
Anti-Infective Agents / chemistry
Anti-Infective Agents / pharmacology*
Bacteria / drug effects*
Bacterial Proteins / biosynthesis
Bacterial Proteins / drug effects
Bombyx / drug effects
DNA, Bacterial / biosynthesis
DNA, Bacterial / drug effects
Fungi / drug effects*
Lethal Dose 50
Microbial Sensitivity Tests
Peptidoglycan / biosynthesis
Peptidoglycan / drug effects
Pyrimidinones / chemistry
Pyrimidinones / pharmacology*
Pyrimidinones / toxicity
RNA, Bacterial / biosynthesis
RNA, Bacterial / drug effects
Staphylococcus aureus / drug effects*
Structure-Activity Relationship
Toxicity Tests / methods
|
| IF |
2.668
|
| 引用数 |
11
|
|
WOS 分野
|
BIOTECHNOLOGY & APPLIED MICROBIOLOGY
PHARMACOLOGY & PHARMACY
MICROBIOLOGY
IMMUNOLOGY
|
| リソース情報 |
| カイコ |
|
| 一般微生物 |
JCM 2499
JCM 5671
JCM 5708
JCM 20037 |
