Hetacillin: A Chemical and Biological Comparison with Ampicillin

Smith, J. T.; Hamilton‐Miller, J. M. T.

doi:10.1159/000220703

Cited by 19 publications

(4 citation statements)

References 7 publications

(14 reference statements)

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“…Hetacillin is a β-lactam antibiotic that was used to treat bacterial infections (Hardcastle Jr et al 1966 ; Smith and Hamilton-Miller 1970 ). It was later withdrawn as it offered a lesser therapeutic value than the ampicillin derivatives.…”

Section: Resultsmentioning

confidence: 99%

Identification of a repurposed drug as an inhibitor of Spike protein of human coronavirus SARS-CoV-2 by computational methods

et al. 2020

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Severe acute respiratory syndrome coronavirus (SARS-CoV-2) is an emerging new viral pathogen that causes severe respiratory disease. SARS-CoV-2 is responsible for the outbreak of COVID-19 pandemic worldwide. As there are no confirmed antiviral drugs or vaccines currently available for the treatment of COVID-19, discovering potent inhibitors or vaccines are urgently required for the benefit of humanity. The glycosylated Spike protein (S-protein) directly interacts with human angiotensin-converting enzyme 2 (ACE2) receptor through the receptor-binding domain (RBD) of S-protein. As the S-protein is exposed to the surface and is essential for entry into the host, the S-protein can be considered as a first-line therapeutic target for antiviral therapy and vaccine development. In silico screening, docking, and molecular dynamics simulation studies were performed to identify repurposing drugs using DrugBank and PubChem library against the RBD of S-protein. The study identified a laxative drug, Bisoxatin (DB09219), which is used for the treatment of constipation and preparation of the colon for surgical procedures. It binds nicely at the S-protein-ACE2 interface by making substantial p-p interactions with Tyr505 in the 'Site 1' hook region of RBD and hydrophilic interactions with Glu406, Ser494, and Thr500. Bisoxatin consistently binds to the protein throughout the 100 ns simulation. Taken together, we propose that the discovered molecule, Bisoxatin may be a promising repurposable drug molecule to develop new chemical libraries for inhibiting SARS-CoV-2 entry into the host.

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Section: Resultsmentioning

confidence: 99%

Identification of a repurposed drug as an inhibitor of Spike protein of human coronavirus SARS-CoV-2 by computational methods

et al. 2020

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“…Concentrations of 10 and 1 ,g of hetacillin/ml with j-lactamase did not inhibit, whereas similar concentrations of ampicillin did. (2,5,6) because they used methods which were too slow to show inhibition of growth occurring within the hydrolysis time of the antibiotic.…”

Section: Resultsmentioning

confidence: 99%

“…It is unstable under conditions of acidity and temperature suitable for antibiotic action, breaking down to ampicillin and acetone (2,5,6). The half-life of hetacillin at 37 C at pH 7.0 has been estimated at 15 to 30 min (2,6).…”

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confidence: 99%

Independent Antibiotic Actions of Hetacillin and Ampicillin Revealed by Fast Methods

Faine

Harper

1973

Antimicrob Agents Chemother

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Fast methods for measuring inhibition of growth of Escherichia coli or Staphylococcus aureus by hetacillin or ampicillin showed that the rate of inhibition was a function of the antibiotic concentration. When ampicillin concentrations were measured rapidly, hetacillin was shown to have a half-life of 20 min at 37 C and pH 6.7. Hetacillin was much less susceptible to penicillinase (f8-lactamase) than was ampicillin. An inhibitory effect of hetacillin was shown in the presence of 1l-lactamase, which destroyed ampicillin activity very rapidly.Hetacillin is an acetone-condensation derivative of ampicillin (1, 6). It is unstable under conditions of acidity and temperature suitable for antibiotic action, breaking down to ampicillin and acetone (2, 5, 6). The half-life of hetacillin at 37 C at pH 7.0 has been estimated at 15 to 30 min (2, 6). In none of the previous studies could the authors demonstrate an independent antibiotic action of hetacillin which could not possibly be attributed to ampicillin.In this study, very rapid, instrumented methods were used to investigate the general problem of how to measure antibiotic activity of an unstable compound whose half-life is not much longer than the replication time of the test bacteria and whose breakdown product has an antibacterial action similar to that of the parent antibiotic. To measure bacterial growth and inhibition, a culture was prepared in its logarithmic growth phase by incubating 0.1 ml of an overnight meat infusion broth culture in 50 ml of the same medium at 37 C for 1.5 hr. A volume of 0.25 ml of antibiotic solution at 10 times the final concentration to be used and 0.1 ml of either 0.05 M phosphate buffer (pH 6.7) or a 1:10 dilution of ,-lactamase (2.5 units) were incubated for 5 min in a 1-cm spectrophotometer cuvette. Then 2.25 ml of the log-phase culture was added, containing between 2 x 106 and 4 x 106 bacteria/ml (viable count, corresponding to an optical density of 0.064 for E. coli 014 and 0.060 for S. aureus S1). The cuvette was incubated at 37 C in a water-jacketed holder in a Unicam SP600 series 2 spectrophotometer, and the optical density at 540 nm was recorded on a Watanabe X-YT/XT recorder (model WX431) fitted with a roll chart moving at 2 mm/min. In some experiments, the output from the spectrophotometer was amplified 10 times with a Keithley model 604 differential amplifier before recording. A similar control culture without antibiotic was incubated simultaneously, and recordings of optical density were made alternately from the test and the control for periods of approximately 1 or 2 min throughout a total time of 10 min to 4 hr in different experiments. MATERIALS AND METHODSAmpicillin was measured by adapting the penicillinase iodometric titration method (4) from the micromethod modification of Novick (3). Penicillinase (,-lactamase) reacts with ampicillin to produce penicilloic acid, which decolorizes starch-iodine reagent at a rate corresponding to its concentration. Starchiodide reagent was prepared from a solution of 0.08 M I, in 3.2...

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“…Ampicillin, a semi-synthetic: antibiotic active against many Gram-positive and Gramnegative bacteria, is widely prescribed in veterinary medicine for treating pneumonia and septicaemia. In relation to plasma and serum concentrations the pharmacokinetics of ampicillin and of its derivatives are well understood (Smith & Hamilton-Miller, 1970;Tan et al, 1974;Ziv et al, 1977). Ampicillin is also given orally in neonatal diarrhoea therapy in the calf (Jones, 1974;Rolinson & Stevens, 1961).…”

Section: Introductionmentioning

confidence: 99%

Ampicillin Inactivation in the Caecum of Axenic, Gnotoxenic and Conventional Lambs: Interaction with Resistant or Sensitive Escherichia coli

Coste¹,

Gouet²,

Escoula³

1984

Microbiology

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The fate of orally administered ampicillin was studied in axenic lambs, in gnotoxenic lambs given a complex microflora and a mixture of ampicillin resistant and/or sensitive strains of Escherichia coli, and in conventional lambs. In axenic lambs or animals with a sensitive microflora, antibiotic concentrations of 500-1600 micrograms ml-1 were detected in the intestine, and most of the ampicillin passed through the small intestine and entered the large intestine, within 12-15 h of administration. These antibiotic concentrations were sufficient to decrease the numbers of ampicillin-sensitive E. coli from 10(8)-10(9) bacteria ml-1 to about 10(5)-10(6) bacteria ml-1 by 8 h after ampicillin administration. Second and third doses of antibiotic had no further effect on the bacterial count. Administration of ampicillin to animals hosting ampicillin-resistant E. coli resulted in a significant inactivation of the antibiotic in the intestine. As might be expected there was little reduction in the numbers of these organisms. These results are similar to those observed in conventional lambs hosting resistant E. coli as the dominant colibacillary flora.

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Hetacillin: A Chemical and Biological Comparison with Ampicillin

Cited by 19 publications

References 7 publications

Identification of a repurposed drug as an inhibitor of Spike protein of human coronavirus SARS-CoV-2 by computational methods

Identification of a repurposed drug as an inhibitor of Spike protein of human coronavirus SARS-CoV-2 by computational methods

Independent Antibiotic Actions of Hetacillin and Ampicillin Revealed by Fast Methods

Ampicillin Inactivation in the Caecum of Axenic, Gnotoxenic and Conventional Lambs: Interaction with Resistant or Sensitive Escherichia coli

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