ChemInform Abstract: HYDROLYSIS OF 3‐CHLORO‐3‐CEPHEMS. INTRAMOLECULAR NUCLEOPHILIC ATTACK IN CEFACLOR

Indelicato, Joseph M.; Dinner, A.; Peters, Lynn R.; Wilham, William L.

doi:10.1002/chin.197742395

Cited by 3 publications

(3 citation statements)

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“…The more reactive cephalosporins have R2 groups with comparatively unstable bonds to the core. The leaving of these groups causes intramolecular electron shifts that destabilize the beta-lactam ring and favor acylation of the nucleophilic sites of the molecular targets [20]. As a result of its acetoxy leaving group, the lactam ring of cephaloglycin is nine times more reactive than that of cephalexin.…”

Section: Reactivity: Acylation Of Target Proteinsmentioning

confidence: 99%

Nephrotoxicity of beta-lactam antibiotics: mechanisms and strategies for prevention

Tune

1997

Pediatr Nephrol

124

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The nephrotoxic beta-lactam antibiotics cause acute proximal tubular necrosis. Significant renal toxicity, which has been rare with the penicillins and uncommon with the cephalosporins, is a greater risk with the penems. Mechanisms of injury include: (1) transport into the tubular cell, mainly through the antiluminal organic anion secretory carrier; (2) acylation of target proteins, causing respiratory toxicity by inactivation of mitochondrial anionic substrate carriers; and (3) lipid peroxidation. The most nephrotoxic beta-lactams available for study are cephaloridine, cephaloglycin, and imipenem; panipenem, which is comparably nephrotoxic, is currently available only in Japan. Cephaloridine has several unique properties, probably all caused by its pyridinium side-group: (1) its secretory transport into the tubular cell is followed by minimal cell to luminal fluid movement, resulting in extreme intracellular sequestration; (2) it is the only beta-lactam shown to cause significant oxidative injury; (3) it has a limited ability to attack the mitochondrial carriers for pyruvate and the short-chain fatty anions. Cephaloglycin and imipenem undergo less intracellular trapping than cephaloridine, but have sufficient tubular cell uptake, reactivity, and generalized toxicity to mitochondrial substrate carriers to be severely nephrotoxic. Cephaloridine and cephaloglycin are no longer used clinically. Imipenem and panipenem are marketed in combination with nephroprotective renal transport inhibitors. Strategies for avoiding renal toxicity with new cephalosporins and penems are discussed.

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Section: Reactivity: Acylation Of Target Proteinsmentioning

confidence: 99%

Nephrotoxicity of beta-lactam antibiotics: mechanisms and strategies for prevention

Tune

1997

Pediatr Nephrol

124

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“…This resonance form is one of those advanced to account for the facile SNI displacement of the 3'-acetoxy group. Whether the effects derive from the loss of the 3'-substituent, or only from its inductive effect on the p-Iactam ring, the reactivity (rate of hydrolysis) of the p-Iactam ring has been shown to correlate with the 0'1 values of 3-methylene substituents (INDELICATO et al 1974); and the rate ofring opening has been shown to be directly proportional to the intrinsic activity of cephalosporins against gramnegative bacteria (INDELICATO et al 1977).…”

Section: D) Effects Of 3'-substituents On In Vitro Activitymentioning

confidence: 99%

β-Lactam Antibiotics: Structure-Activity Relationships

Hoover¹

1983

Antibiotics

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“…Cephalosporins can decompose inter-or intramolecularly (Scheme 9) (Cohen et a1 1973;Bundgaard 1976aBundgaard , b, 1977Yawana & Tsuji 1976;Dinner 1977;Indelicato et a1 1977;Tsuji et a1 1981).…”

Section: Fl-lactam Antibioticsmentioning

confidence: 99%

Effect of Detergents and Other Amphiphiles on the Stability of Pharmaceutical Drugs

Oliveira¹,

Chaimovich

1993

Journal of Pharmacy and Pharmacology

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ChemInform Abstract: HYDROLYSIS OF 3‐CHLORO‐3‐CEPHEMS. INTRAMOLECULAR NUCLEOPHILIC ATTACK IN CEFACLOR

Cited by 3 publications

References 1 publication

Nephrotoxicity of beta-lactam antibiotics: mechanisms and strategies for prevention

Nephrotoxicity of beta-lactam antibiotics: mechanisms and strategies for prevention

β-Lactam Antibiotics: Structure-Activity Relationships

Effect of Detergents and Other Amphiphiles on the Stability of Pharmaceutical Drugs

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