New class of semisynthetic penicillins and cephalosporins derived from D-2-(1,4-cyclohexadienyl)glycine

Dolfini, J. E.; Applegate, H. E.; Bach, Georges; Basch, Harold; Bernstein, Jack; Schwartz, Joseph A.; Weisenborn, Frank L.

doi:10.1021/jm00284a008

Cited by 41 publications

(15 citation statements)

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“…More recently other aminopenicillins have been in troduced. One such compound epicillin, in which the benzene ring of ampicillin has been replaced by a cyclohexadienyl ring, was first described in 1971 [6] and was re ported to have an antibacterial spectrum very similar to that of ampicillin but to be more active than ampicillin against Pseudo monas aeruginosa [2,7]. Amoxycillin, which differs from ampicillin in having a p-hydroxy group in the benzene ring, was also described in 1971 [14] as a compound showing similar activity to ampicillin but which had much improved oral absorption [5] and was more active in vivo [1].…”

Section: Introductionmentioning

confidence: 99%

Comparative Activities of Ampicillin, Epicillin and Amoxycillin in vitro and in vivo

Basker¹,

Gwynn²,

White³

1979

Chemotherapy

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The antibacterial activities of three aminopenicillins ampicillin, epicillin and amoxycillin were compared in vitro and in vivo. The minimum inhibitory concentrations (MIC) of the three penicillins were very similar and the compounds were active against non-β-lactamase-producing strains of Escherichia coli, Salmonella and Shigella species, Proteus mirabilis, Haemophilus influenzae and Neissería gonorrhoeae. Streptococci including Streptococcus faecalis, and non-β-lactamase-producing staphylococci were also sensitive to the compounds but Pseudomonas aeruginosa, Klebsiella aerogenes, Enterobacter and indole-positive Proteus species were resistant. At concentrations close to MIC value epicillin and ampicillin showed similar bactericidal activity against E. coli and against S. typhi and both compounds caused a slower rate of kill than was seen with amoxycillin. Microscopical observation of the cells exposed to ampicillin and epicillin for 1 h showed the presence of filamentous forms which lysed slowly, whereas cells exposed to amoxycillin for the same period lysed rapidly. Epicillin was similar to or slightly less active than ampicillin against experimental mouse infections, and against the majority of infections both compounds were significantly less effective than amoxycillin by the oral and subcutaneous routes of administration.

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Section: Introductionmentioning

confidence: 99%

Comparative Activities of Ampicillin, Epicillin and Amoxycillin in vitro and in vivo

Basker¹,

Gwynn²,

White³

1979

Chemotherapy

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“…The broad spectrum of antibacterial activity demonstrated by these antibiotics and their resistailce to degradation by penicillinases have made them particularly well accepted. A new member of this group, cephradine, is [7-D(-)-2-amino-2-(1, 4-cyclohexadien-1-yl)acetamido]-3-methyl-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid hydrite (1). Previous studies (H. H. Gadebusch et al, Progr.…”

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confidence: 99%

Comparison of the Chemotherapeutic and Pharmacodynamic Activities of Cephradine, Cephalothin, and Cephaloridine in Mice

Miraglia

Renz

Gadebusch

1973

Antimicrob Agents Chemother

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Cephradine, a new semisynthetic cephalosporin derivative, is 7[D(-)-2-amino-2-(1 ,4-cyclohexadien-1-yl)acetamido]-3-methyl-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid hydrate. The compound has a broad spectrum of antimicrobial activity in vitro. When given subcutaneously to mice, cephradine was appreciably more effective than cephalothin against infections induced by penicillinase-producing Staphylococcus, Escherichia coli, Klebsiella pneumoniae, or Enterobacter cloacae strains. Cephradine and cephaloridine possessed equivalent activity in treating infections caused by these same three gram-negative bacteria. The mean total bioactivity of cephradine in the serum of mice peaked within 30 min (59 ug/ml) after parenteral administration and was approximately threefold that of cephalothin (20 pg/ml), but less than that of cephaloridine (83 ug/ml). Nearly all of the administered cephradine (84%) and cephaloridine (70%) were excreted in the urine as the parent compounds. In contrast, only 47% (total bioactivity) of administered cephalothin was recovered, an amount that represented only 15 to 20% of the parent substance.

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“…Dogs given Cephradine for Injection intravenously for 4 weeks at total daily doses of 80, 240, or 800 mg of cephradine/kg showed no significant signs of toxicity and no gross or micro- scopic changes that could be attributed to the compound. In a similar study, rhesus monkeys were given intravenous doses of cephradine or cephaloridine for 2 weeks at total daily doses of 60, 180, or 600 mg/kg.…”

Section: Resultsmentioning

confidence: 95%

“…Especially to be desired were broadening of the antimicrobial spectrum, more efficient absorption after oral administration, and greater resistance to metabolic degradation. (4). The antimicrobial activities in vitro of cephradine, and its chemotherapeutic efficacy in animals after oral administration, have been described recently (H. Gadebusch et al, Progr.…”

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confidence: 98%

Toxicological, Pathological, and Teratological Studies in Animals with Cephradine

Hassert¹,

Debaecke²,

Kulesza³

et al. 1973

Antimicrob Agents Chemother

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Cephradine, a semisynthetic cephalosporin antibiotic, has a low order of oral and parenteral toxicity in animals. The oral LD,0 in mice and rats ranged from 5 to >8 g/kg, and the intraperitoneal LD50 values in mice and rats were 0.7 to 1.5 g/kg and 4.0 g/kg, respectively. The intravenous LD50 in mice ranged from 3.0 to 3.8 g/kg. In anesthetized dogs, intravenous doses of cephradine (40 and 120 mg/kg, given 45 min apart) had no effect on either the renal or cardiovascular systems. Single intramuscular injections (0.25 ml or 0.5 ml of a solution containing 125 to 235 mg of cephradine/ml) elicited no signs of either pain or local irritation in dogs, and only transient signs of slight-to-moderate irritation were observed in rabbits. In subacute toxicity studies, cephradine was administered for 4 weeks to rats (daily intraperitoneal doses of 160, 480, or 1,600 mg/kg) and dogs (daily intravenous doses of 80, 240, or 800 mg/kg); in addition, over a 2-week period, monkeys were given daily intravenous doses of 60, 180, or 600 mg/kg. No clinical, biochemical, gross, or micropathological changes due to cephradine were observed in these animals; especially notable was the absence of any signs of nephrotoxicity. In chronic toxicity studies, daily doses of cephradine were administered orally to rats (100 to 1,000 mg/kg), dogs (50 to 500 mg/kg), and monkeys (50 to 500 mg/kg) for 26, 26, and 13 weeks, respectively. Significant responses were observed only in rats, in which grossly enlarged, but histologically normal, ceca developed, a common finding in rodents dosed with antibiotics; in addition, there were increases in the relative and absolute weights of the adrenal glands. None of these effects was observed in rats that were necropsied 3 weeks after termination of dosage. In reproduction studies in mice and rats given either daily oral doses (100 or 300 mg/lkg) or daily intraperitoneal doses (rats only; 80 or 320 mg/kg) of cephradine, no drug-related teratogenic changes in the offspring were observed.

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New class of semisynthetic penicillins and cephalosporins derived from D-2-(1,4-cyclohexadienyl)glycine

Cited by 41 publications

References 0 publications

Comparative Activities of Ampicillin, Epicillin and Amoxycillin <i>in vitro</i> and <i>in vivo</i>

Comparative Activities of Ampicillin, Epicillin and Amoxycillin <i>in vitro</i> and <i>in vivo</i>

Comparison of the Chemotherapeutic and Pharmacodynamic Activities of Cephradine, Cephalothin, and Cephaloridine in Mice

Toxicological, Pathological, and Teratological Studies in Animals with Cephradine

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