一种具有双重作用模式的新型头孢菌素。
A new cephalosporin with a dual mode of action.
作者信息
O'Callaghan C H, Sykes R B, Staniforth S E
出版信息
Antimicrob Agents Chemother. 1976 Aug;10(2):245-8. doi: 10.1128/AAC.10.2.245.
Abstract
A cephalosporin, (6R,7R)-7-[(2R)-2-hydroxy-2-phenylacetamido]-3-(pyrid-2-yl-N-oxide) thiomethylceph-3-em-4-carboxylic acid (MCO), that could lead to a novel approach to the problem of beta-lactamase destruction is described. The compound is slightly more resistant to some beta-lactamases than is cephalothin, but it is still hydrolyzed by many to a varying degree. Hydrolysis of the beta-lactam bond of a cephalosporin releases the 3-substituent, which in MCO is itself an antibacterial agent, 2-mercaptopyridine-N-oxide. Thus, MCO has a dual mode of action, and bacteria that do not produce an effective amount of a beta-lactamase are inhibited by the intact cephalosporin, whereas those that do hydrolyze it are inhibited by the released antibacterial compound.
摘要
一种头孢菌素，即(6R,7R)-7-[(2R)-2-羟基-2-苯乙酰氨基]-3-(吡啶-2-基-N-氧化物)硫代甲基头孢-3-烯-4-羧酸（MCO），它为解决β-内酰胺酶破坏问题提供了一种新方法。该化合物对某些β-内酰胺酶的耐药性略高于头孢噻吩，但仍会被许多β-内酰胺酶不同程度地水解。头孢菌素β-内酰胺键的水解会释放3-取代基，在MCO中该取代基本身就是一种抗菌剂，即2-巯基吡啶-N-氧化物。因此，MCO具有双重作用模式，不产生有效量β-内酰胺酶的细菌会被完整的头孢菌素抑制，而那些水解该头孢菌素的细菌则会被释放出的抗菌化合物抑制。
相似文献
1
A new cephalosporin with a dual mode of action.一种具有双重作用模式的新型头孢菌素。
Antimicrob Agents Chemother. 1976 Aug;10(2):245-8. doi: 10.1128/AAC.10.2.245.
2
The comparative beta-lactamase resistance and inhibitory activity of 1-oxa cephalosporin, cefoxitin and cefotaxime.1-氧杂头孢菌素、头孢西丁和头孢噻肟的β-内酰胺酶耐药性及抑制活性比较
J Antibiot (Tokyo). 1979 Sep;32(9):909-14. doi: 10.7164/antibiotics.32.909.
3
Comparative in vitro activity and beta-lactamase stability of moxalactam and other selected cephalosporin antibiotics.羟羧氧酰胺菌素及其他选定头孢菌素抗生素的体外活性及β-内酰胺酶稳定性比较
Arzneimittelforschung. 1981;31(8):1290-5.
4
In vitro antibacterial activity and beta-lactamase stability of SCE-129, a new cephalosporin.新型头孢菌素SCE - 129的体外抗菌活性及β - 内酰胺酶稳定性
Antimicrob Agents Chemother. 1979 May;15(5):646-50. doi: 10.1128/AAC.15.5.646.
5
In vitro activity and beta-lactamase stability of cefazaflur compared with those of beta-lactamase-stable cephalosporins.头孢扎氟的体外活性及β-内酰胺酶稳定性与β-内酰胺酶稳定型头孢菌素的比较。
Antimicrob Agents Chemother. 1979 Mar;15(3):444-6. doi: 10.1128/AAC.15.3.444.
6
Antibacterial activity of ceftizoxime (FK 749), a new cephalosporin, against cephalosporin-resistant bacteria, and its stability to beta-lactamase.新型头孢菌素头孢唑肟（FK 749）对耐头孢菌素细菌的抗菌活性及其对β-内酰胺酶的稳定性。
Antimicrob Agents Chemother. 1979 Nov;16(5):549-53. doi: 10.1128/AAC.16.5.549.
7
In vitro activity and beta-lactamase stability of BL-S786 compared with those of other cephalosporins.BL-S786与其他头孢菌素相比的体外活性及β-内酰胺酶稳定性。
Antimicrob Agents Chemother. 1978 Jul;14(1):1-5. doi: 10.1128/AAC.14.1.1.
8
In vitro activity and beta-lactamase stability of U-63196E, a novel cephalosporin.新型头孢菌素U-63196E的体外活性及β-内酰胺酶稳定性
Antimicrob Agents Chemother. 1983 Sep;24(3):375-82. doi: 10.1128/AAC.24.3.375.
9
Cefuroxime, a new cephalosporin antibiotic: activity in vitro.头孢呋辛，一种新型头孢菌素抗生素：体外活性
Antimicrob Agents Chemother. 1976 Mar;9(3):511-9. doi: 10.1128/AAC.9.3.511.
10
Semisynthetic beta-lactam antibiotics. III. Cephalosporin derivatives in the furyl series. Chemical and microbiological properties.
J Antibiot (Tokyo). 1980 Oct;33(10):1177-82. doi: 10.7164/antibiotics.33.1177.
引用本文的文献
1
Tackling the outer membrane: facilitating compound entry into Gram-negative bacterial pathogens.攻克外膜：促进化合物进入革兰氏阴性菌病原体。
NPJ Antimicrob Resist. 2023 Dec 20;1(1):17. doi: 10.1038/s44259-023-00016-1.
2
Microneedles as a potential platform for improving antibiotic delivery to bacterial infections.微针作为改善抗生素向细菌感染部位递送的潜在平台。
Heliyon. 2024 Aug 29;10(17):e37173. doi: 10.1016/j.heliyon.2024.e37173. eCollection 2024 Sep 15.
3
An engineered prodrug selectively suppresses β-lactam resistant bacteria in a mixed microbial setting.一种工程前药在混合微生物环境中选择性抑制β-内酰胺耐药菌。
bioRxiv. 2024 Aug 3:2024.08.02.606422. doi: 10.1101/2024.08.02.606422.
4
The Odd Couple(s): An Overview of Beta-Lactam Antibiotics Bearing More Than One Pharmacophoric Group.《Odd Couple(s): 多药效团β-内酰胺类抗生素概述》
Int J Mol Sci. 2021 Jan 9;22(2):617. doi: 10.3390/ijms22020617.
5
A Cephalosporin Prochelator Inhibits New Delhi Metallo-β-lactamase 1 without Removing Zinc.头孢菌素螯合剂在不除去锌的情况下抑制新德里金属β-内酰胺酶 1。
ACS Infect Dis. 2020 May 8;6(5):1264-1272. doi: 10.1021/acsinfecdis.0c00083. Epub 2020 Apr 29.
6
Dual-Pharmacophore Pyrithione-Containing Cephalosporins Kill Both Replicating and Nonreplicating .含双药效团的吡啶硫酮头孢菌素对复制型和非复制型均有杀灭作用。
ACS Infect Dis. 2019 Aug 9;5(8):1433-1445. doi: 10.1021/acsinfecdis.9b00112. Epub 2019 Jun 11.
7
Exploitation of Antibiotic Resistance as a Novel Drug Target: Development of a β-Lactamase-Activated Antibacterial Prodrug.利用抗生素耐药性作为新型药物靶点：β-内酰胺酶激活型抗菌前药的开发。
J Med Chem. 2019 May 9;62(9):4411-4425. doi: 10.1021/acs.jmedchem.8b01923. Epub 2019 May 1.
8
Copper Influences the Antibacterial Outcomes of a β-Lactamase-Activated Prochelator against Drug-Resistant Bacteria.铜影响β-内酰胺酶激活的前螯合剂对耐药细菌的抗菌效果。
ACS Infect Dis. 2018 Jun 8;4(6):1019-1029. doi: 10.1021/acsinfecdis.8b00037. Epub 2018 Mar 26.
9
Antibiotic Hybrids: the Next Generation of Agents and Adjuvants against Gram-Negative Pathogens?抗生素杂合体：下一代针对革兰氏阴性病原体的药物和佐剂？
Clin Microbiol Rev. 2018 Mar 14;31(2). doi: 10.1128/CMR.00077-17. Print 2018 Apr.
10
Stimulus-Responsive Prochelators for Manipulating Cellular Metals.刺激响应型螯合剂用于操控细胞金属。
Acc Chem Res. 2016 Nov 15;49(11):2468-2477. doi: 10.1021/acs.accounts.6b00380. Epub 2016 Oct 17.
本文引用的文献
1
Toxicology of hydroxypyridinethione.羟基吡啶硫酮的毒理学
Toxicol Appl Pharmacol. 1960 Mar;2:156-70. doi: 10.1016/0041-008x(60)90045-4.
2
Products of aminolysis and enzymic hydrolysis of the cephalosporins.头孢菌素的氨解产物和酶解产物。
Biochem J. 1970 Feb;116(3):371-84. doi: 10.1042/bj1160371.
3
Biological properties of three 3-heterocyclic-thiomethyl cephalosporin antibiotics.三种3-杂环硫甲基头孢菌素抗生素的生物学特性
Antimicrob Agents Chemother. 1972 Mar;1(3):221-34. doi: 10.1128/AAC.1.3.221.
4
The beta-lactamases of gram-negative bacteria and their possible physiological role.革兰氏阴性菌的β-内酰胺酶及其可能的生理作用。
Adv Microb Physiol. 1973;9:31-88. doi: 10.1016/s0065-2911(08)60376-8.
5
Correlation between hydrolysis of the -lactam bond of the cephalosporin nucleus and expulsion of the 3-substituent.头孢菌素核β-内酰胺键的水解与3-取代基的脱去之间的相关性。
J Bacteriol. 1972 Jun;110(3):988-91. doi: 10.1128/jb.110.3.988-991.1972.
6
Novel method for detection of beta-lactamases by using a chromogenic cephalosporin substrate.一种使用显色头孢菌素底物检测β-内酰胺酶的新方法。
Antimicrob Agents Chemother. 1972 Apr;1(4):283-8. doi: 10.1128/AAC.1.4.283.
7
Cefuroxime - a new cephalosporin antibiotic.头孢呋辛——一种新型头孢菌素类抗生素。
J Antibiot (Tokyo). 1976 Jan;29(1):29-37. doi: 10.7164/antibiotics.29.29.
8
Laboratory tests of antifungal drugs.抗真菌药物的实验室检测
J Clin Pathol. 1975 Oct;28(10):767-74. doi: 10.1136/jcp.28.10.767.
Zotero 插件