카테콜 치환체를 가진 세파로스포린계 항생제 LB10522의 작용기전

• 영문명: Action Mechanism of LB10522, a New Catechol-Substituted Cephalosporin
• 발행기관: 대한약학회
• 저자명: 김무용(Mu Yong Kim) 오정인(Jeong In Oh) 백경숙(Kyung Sook Paek) 김인철(In Chull Kim) 곽진환(Jin Hwan Kwak)
• 간행물 정보: 『약학회지』제40권 제1호 (1996년), 102~111쪽, 전체 10쪽
• 주제분류: 의약학 > 기타의약학
• 파일형태: PDF
• 발행일자: 1996.02.28

영문 초록

LB10522 is a new parenteral broad spectrum cephalosporin with a catechol moiety at C-7 position of beta-lactam ring. This compound can utilize tonB-dependent iron transport system in addition to porin proteins to enter bacteria] periplasmic space and access to penicillin-binding proteins (PBPs) which are the lethal targets of beta-lactam antibiotics. The chelating activity of LB10522 to metal iron was measured by spectrophotometrically scanning the absorbance from 200 to 900nm. When FeCl3 was added, optical density was increased between 450 and 800nm. LB10522 was more active against gram-negative strains in iron-depleted media than in iron-replete media. This is due to the increased expression of iron transport channels in iron-depleted condition. LB10522 showed a similar activity against E. coli DC2 (permeability mutant) and E. coli DCO (wild type strain) in both iron-depleted and iron-replete media, indicating a minimal permeaility barrier for LB10522 uptake. LB10522 had high affinities to PBP 3 and PBP 1A, 1B of E. coli. By blocking these proteins, LB10522 caused inhibition of cell division and the eventual death of cells. This result was correlated well with the morphological changes in E. coli exposed to LB10522. Although the in vitro MIC of LB10522 against P. aeruginosa 1912E mutant (tonB) was 8-times higher than that of the P. aeruginosa 1912E parent strain, LB10522 showed a similar in vivo protection efficacy against both strains in the mouse systemic infection model. This result suggested that tonB mutant, which requires a high level of iron for normal growth, might have a difficulty in surviving in their host with an iron-limited environment.

키워드

Cephalosporin Catechol PBP(Penicillin Binding Protein) tonB LB10522.