SOME BIOLOGICAL PROPERTIES OF CEPHALOSPORIN P<sub>1</sub>

Ritchie, A. C.; Smith, N.; Florey, H. W.

doi:10.1111/j.1476-5381.1951.tb00653.x

Cited by 15 publications

(10 citation statements)

References 12 publications

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“…7 Early work demonstrated that 1 has an antibacterial spectrum that predominantly encompasses Gram-positive organisms, with particularly potent activity against SA. 8, 9 This is the first time that 1 and 2 were isolated from H. irregularis . The NMR data of 2 were not completely assigned in the previous work.…”

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confidence: 90%

Three new fusidic acid derivatives and their antibacterial activity

Zhang¹,

Wang²,

Zhang³

et al. 2015

Bioorganic & Medicinal Chemistry Letters

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Two steroid acids, cephalosporin P1 and isocephalosporin P1, were isolated from Hapsidospora irregularis FERM BP-2511. These compounds are structurally related to fusidic acid. Their NMR data were completely assigned on the basis of the 2D NMR spectra. Incubation of these two compounds with Microbaterium oxydans CGMCC 1788 in Luria-Bertani broth yielded the same set of three new 3-dehydrogenated products, 3-keto-isocephalosporin P1, 3-keto-cephalosporin P1 and 6-deacetyl-3-keto-cephalosporin P1. The final pH of the bacterial culture was 9.0. Incubation of 3-keto-isocephalosporin P1 or 3-keto-cephalosporin P1 in Tris-HCl buffer (pH 9.0) revealed that these two compounds can convert to each other by shifting the acetyl group between C-6 and C-7. The acetyl group at C-6 or C-7 can also be removed by hydrolysis to yield the minor product 6-deacetyl-3-keto-cephalosporin P1. These fusidic acid derivatives were tested for the antibacterial activity against the Gram-positive pathogen Staphylococcus aureus. 3-Keto-cephalosporin P1 showed the highest activity among the five compounds, with a minimal inhibition concentration (MIC) of 4 μg/mL, which is more potent than the substrate cephalosporin P1. Both cephalosporin P1 and 3-keto-cephalosporin P1 were active against methicillin-resistant S. aureus, with the same MIC of 8 μg/mL.

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confidence: 90%

Three new fusidic acid derivatives and their antibacterial activity

Zhang¹,

Wang²,

Zhang³

et al. 2015

Bioorganic & Medicinal Chemistry Letters

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“…Cephalosporin P suffers from the defect that resistance to it is rapidly acquired, especially in a dense bacterial population: the results of a test of bactericidal action with a large inoculum show that this change can make considerable progress overnight. Ritchie et al (1951) did not observe increased resistance in vivo, although therapeutic effect was poor: this point perhaps deserves to be further explored. Micrococcin P suffers from the same defect to perhaps an even greater degree, and has the further disadvantage of very low solubility, which would render administration difficult.…”

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confidence: 84%

Leprosy: A Changing Situation in Eastern Nigeria

Davey¹,

Ross²,

Nicholson³

1956

BMJ

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“…It is instructive that LEO's first real successful hit came when they examined the antibiotic potential of a genus of molds not tested previously, although related compounds, helvolic acid and cephalosporin P1 produced by other genera of molds were discovered much earlier, in 1943 and 1951 (Ritchie et al, 1951;Chain et al, 1953;Burton et al, 1956). Searching for new antibiotics among taxonomic groups of poorly characterized microorganisms remains one of the strategies for screenings programs today, with the discovery of teixobactin as one of many examples (Peláez, 2006;Aminov, 2010Aminov, , 2017Lewis, 2013Lewis, , 2015Genilloud, 2014;Ling et al, 2015).…”

Section: The Case For Serendipity: Discovery Of Fusidic Acid In 1960mentioning

confidence: 99%

The Diverse Search for Synthetic, Semisynthetic and Natural Product Antibiotics From the 1940s and Up to 1960 Exemplified by a Small Pharmaceutical Player

Leisner

2020

Front. Microbiol.

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The 1940s and 1950s witnessed a diverse search for not just natural product antibiotics but also for synthetic and semisynthetic compounds. This review revisits this epoch, using the research by a Danish pharmaceutical company, LEO Pharma, as an example. LEO adopted a strategy searching for synthetic antibiotics toward specific bacterial pathogens, in particular Mycobacterium tuberculosis, leading to the discovery of a new derivative of a known drug. Work on penicillin during and after WWII lead to the development of associated salts/esters and a search for new natural product antibiotics. This led initially to no new, marketable compounds, but concluded with the serendipitous discovery of fusidic acid, an antibiotic used to treat infections by Staphylococcus aureus, in 1960. The discovery process included contemporary approaches such as open innovation; targeting specific pathogens and/or specific organs in the patient; examining the effects of antimicrobial compounds on bacterial virulence as well as on antibioticresistant variants, and searching for antibiotic producers among microorganisms not previously well explored. These activities were promoted by the collaboration with a renowned Danish clinical microbiologist, K. A. Jensen, as well as company expertise in fermentation technologies, chemical synthesis and purification of bioactive compounds from organic materials.

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SOME BIOLOGICAL PROPERTIES OF CEPHALOSPORIN P₁

Cited by 15 publications

References 12 publications

Three new fusidic acid derivatives and their antibacterial activity

Three new fusidic acid derivatives and their antibacterial activity

Leprosy: A Changing Situation in Eastern Nigeria

The Diverse Search for Synthetic, Semisynthetic and Natural Product Antibiotics From the 1940s and Up to 1960 Exemplified by a Small Pharmaceutical Player

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SOME BIOLOGICAL PROPERTIES OF CEPHALOSPORIN P1

Cited by 15 publications

References 12 publications

Three new fusidic acid derivatives and their antibacterial activity

Three new fusidic acid derivatives and their antibacterial activity

Leprosy: A Changing Situation in Eastern Nigeria

The Diverse Search for Synthetic, Semisynthetic and Natural Product Antibiotics From the 1940s and Up to 1960 Exemplified by a Small Pharmaceutical Player

Contact Info

Product

Resources

About

SOME BIOLOGICAL PROPERTIES OF CEPHALOSPORIN P₁