Antibacterial substances related to pantothenic acid

Madinaveitia, J.; Martin, Anandi; Rose, F. L.; Swain, G.

doi:10.1042/bj0390085

Cited by 16 publications

(10 citation statements)

References 6 publications

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“…With the aim of preparing pantothenic acid analogues more active than pantoyltaurine in vivo , Madinaveitia et al . (1945) synthesized a number of compounds, among which was pantoylhydrazide ( 26 ).…”

Section: Pantothenic Acid Analogues As Antibacterial and Antifungal Amentioning

confidence: 99%

“…With the aim of preparing pantothenic acid analogues more active than pantoyltaurine in vivo, Madinaveitia et al (1945) synthesized a number of compounds, among which was pantoylhydrazide (26). This analogue demonstrated inhibitory activity somewhat greater than pantoyltaurine against Lactobacillus casei in vitro, and the activity was antagonized specifically by pantothenate.…”

Section: Pantoylhydrazide and Related Compoundsmentioning

confidence: 99%

“…Pantoylhydrazide also inhibited growth of Streptococcus pyogenes in vitro, but failed to show antibacterial activity in rats infected with Streptococcus pyogenes when administered subcutaneously in four doses of 1 g kg À1 body weight over a 12-h period after infection. The simple pantothenic acid analogue pantamide (27), and compounds 28 and 29, were also shown by Madinaveitia et al (1945) to possess antibacterial activity against Lactobacillus casei in vitro. The activity of the two former compounds was antagonized by pantothenate, while the antibacterial activity of the latter appeared to be independent of the concentration of pantothenate present in the medium.…”

Section: Pantoylhydrazide and Related Compoundsmentioning

confidence: 99%

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Coenzyme A biosynthesis: an antimicrobial drug target

Spry¹,

Kirk²,

Saliba³

2008

FEMS Microbiol Rev

245

260

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Pantothenic acid, a precursor of coenzyme A (CoA), is essential for the growth of pathogenic microorganisms. Since the structure of pantothenic acid was determined, many analogues of this essential metabolite have been prepared. Several have been demonstrated to exert an antimicrobial effect against a range of microorganisms by inhibiting the utilization of pantothenic acid, validating pantothenic acid utilization as a potential novel antimicrobial drug target. This review commences with an overview of the mechanisms by which various microorganisms acquire the pantothenic acid they require for growth, and the universal CoA biosynthesis pathway by which pantothenic acid is converted into CoA. A detailed survey of studies that have investigated the inhibitory activity of analogues of pantothenic acid and other precursors of CoA follows. The potential of inhibitors of both pantothenic acid utilization and biosynthesis as novel antibacterial, antifungal and antimalarial agents is discussed, focusing on inhibitors and substrates of pantothenate kinase, the enzyme catalysing the rate-limiting step of CoA biosynthesis in many organisms. The best strategies are considered for identifying inhibitors of pantothenic acid utilization and biosynthesis that are potent and selective inhibitors of microbial growth and that may be suitable for use as chemotherapeutic agents in humans.

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Section: Pantothenic Acid Analogues As Antibacterial and Antifungal Amentioning

confidence: 99%

Section: Pantoylhydrazide and Related Compoundsmentioning

confidence: 99%

Section: Pantoylhydrazide and Related Compoundsmentioning

confidence: 99%

See 1 more Smart Citation

Coenzyme A biosynthesis: an antimicrobial drug target

Spry¹,

Kirk²,

Saliba³

2008

FEMS Microbiol Rev

245

260

View full text Add to dashboard Cite

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“…In the past 60 years, there have been numerous reports on the synthesis of pantothenic acid analogs with inhibitory activity against a range of pantothenic acid-requiring microorganisms (3,10,17,19). For the majority of analogs, the inhibitory activity was antagonized by pantothenic acid, consistent with their inhibitory effect being due to their interference with pantothenic acid utilization (10,17). A selection of these compounds was tested against avian malaria parasites in vivo and demonstrated potent antiplasmodial activity (2).…”

mentioning

confidence: 92%

“…One nutrient for which the parasite has an absolute requirement is pantothenic acid (vitamin B 5 ; see Table 1 for its structure) (5,13), the precursor of the essential enzyme cofactor coenzyme A. In the past 60 years, there have been numerous reports on the synthesis of pantothenic acid analogs with inhibitory activity against a range of pantothenic acid-requiring microorganisms (3,10,17,19). For the majority of analogs, the inhibitory activity was antagonized by pantothenic acid, consistent with their inhibitory effect being due to their interference with pantothenic acid utilization (10,17).…”

mentioning

confidence: 99%

A Class of Pantothenic Acid Analogs Inhibits Plasmodium falciparum Pantothenate Kinase and Represses the Proliferation of Malaria Parasites

Spry¹,

Chai

Kirk³

et al. 2005

Antimicrob Agents Chemother

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The growth and proliferation of the human malaria parasite Plasmodium falciparum are dependent on the parasite's ability to obtain essential nutrients. One nutrient for which the parasite has an absolute requirement is the water-soluble vitamin pantothenic acid (vitamin B 5 ). In this study, a series of pantothenic acid analogs which retain the 2,4-dihydroxy-3,3-dimethylbutyramide core of pantothenic acid but deviate in structure from one another and from pantothenic acid in the nature of the substituent attached to the amide nitrogen were synthesized using an efficient single-step synthetic route. Eight of 10 analogs tested inhibited the proliferation of intraerythrocytic P. falciparum parasites in vitro, doing so with 50% inhibitory concentrations between 15 and 200 M. The compounds were generally selective, inhibiting the proliferation of a human cell line (the Jurkat cell line) only at concentrations severalfold higher than those required for inhibition of parasite growth. It was demonstrated that compounds in this series inhibited the phosphorylation of pantothenic acid by pantothenate kinase, the first step in the parasite's biosynthesis of the essential enzyme cofactor coenzyme A, doing so competitively, with K i values in the nanomolar range.

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