Pipemidic Acid (syn: piperamic acid) is a pyridopyrimidine antibiotic similar in structure and mechanism to quinolone antibiotics. It is a quinolone derivative, specifically a derivative of piromidic acid. It was introduced in 1979 and and the addition of the piperazinyl side chain at position 7 improved its activity against Gram-negative bacteria and broadened the spectrum to include Psedomonas spp. Its potency is generally greater than piromidic acid and nalidixic acid. The compound can be used to study DNA damage and mutagenic activity, and human blastogenesis and gamma-interferon production.
Pipemidic Acid is slightly soluble in aqueous solution.
| Mechanism of Action | Pipemidic Acid targets bacterial DNA gyrase, an enzyme which reduces DNA strain during replication. Because DNA gyrase is required during DNA replication, subsequent DNA synthesis and ultimately cell division is inhibited. It is bactericidal via inhibition of DNA synthesis. The piperazine ring has also been shown to increase the ability of quinolones to penetrate the bacterial cell wall, thus enhancing its activity. |
| Spectrum | Pipemidic Acid is a broad-spectrum antibiotic covering a wide range of susceptible bacteria. It is active against Gram-negative bacteria (including Pseudoonas aeruginosa) and some Gram-positive bacteria. |
| Impurity Profile | Impurity A| 8-ethyl-2-hydroxy-5-oxo-5,8-dihydropyrido[2,3-d]pyrimidine-6-carboxylic acid|||| Impurity B| 8-ethyl-2-methoxy-5-oxo-5,8-dihydropyrido[2,3-d]pyrimidine-6-carboxylic acid|||| Impurity C| 2-ethoxy-8-ethyl-5-oxo-5,8-dihydropyrido[2,3-d]pyrimidine-6-carboxylic acid|||| Impurity D| ethyl 2-chloro-8-ethyl-5-oxo-5,8-dihydropyrido[2,3-d]pyrimidine-6-carboxylate|||| Impurity E| ethyl 8-ethyl-5-oxo-2-(piperazin-1-yl)-5,8-dihydropyrido[2,3-d]pyrimidine-6-carboxylate|||| Impurity F| 2-(4-acetylpiperazin-1-yl)-8-ethyl-5-oxo-5,8-dihydropyrido[2,3-d]pyrimidine-6-carboxylic acid (acetylpipemidic acid)|||| |
| Microbiology Applications | Pipemidic Acid is commonly used in clinical in vitro microbiological antimicrobial susceptibility tests (panels, discs, and MIC strips) against Gram-positive and Gram-negative microbial isolates. Medical microbiologists use AST results to recommend antibiotic treatment options. Representative MIC values include:
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| Eukaryotic Cell Culture Applications | Pipemidic Acid induced inhibition of lymphocyte DNA synthesis. |
| Molecular Formula | C14H17N5O3 |
| Solubility | Acids and Bases: Soluble Alcohols: Very slightly soluble Water: Very slightly soluble |
| References |
De Simone C et al (1986) Influence of ofloxacin, norfloxacin, nalidixic acid, pyromidic acid and Pipemidic Acid on human gamma-interferon production and blastogenesis. J. Antimicrob. Chemother. 17(6):811-814 PMID 3090010 Katae H and Minami A (1975) Pipemidic Acid, a new antibacterial agent active against Pseudomonas aeruginosa: In vitro properties. Antimicrob. Agents Chemother. 8 (32):132-138 Maura A and Pino A (1988) Evaluation of the DNA-damaging and mutagenic activity of oxolinic and Pipemidic Acids by the granuloma pouch assay. Mutagenesis. 3(5):397-401 PMID 3070273 |
| MIC | Bacillus subtilis| 3.13|| Bacteroides bivius| 25|| Bacteroides distasonis| 100|| Bacteroides fragilis| 200|| Bacteroides gracilis| 6.25|| Bacteroides intermedius| 25|| Bacteroides oralis | 12.5|| Bacteroides oris| 25|| Bacteroides ovatus| 200|| Bacteroides thetaiotaomicron| 200|| Bacteroides uniformis| 100|| Bacteroides ureolyticus| 6.25|| Bacteroides vulgatus| 100|| Bifidobacterium adolescentis| ≤0.025|| Capnocytophaga ochracea | ≤0.025|| Clostridium difficile| >200|| Clostridium perfringens| 25|| Clostridium septicum| 12.5|| Enterobacter aerogenes| 1.56|| Enterobacter cloacae| 1.56|| Escherichia coli| 0.78 - 1.56|| Eubacterium lentum| 50|| Fusobacterium mortiferum| 100|| Fusobacterium varium| 200|| Klebsiella pneumoniae| 1.56|| Peptostreptococcus anaerobius| 50|| Peptostreptococcus asaccharolyticus| 50|| Peptostreptococcus magnus| 100|| Peptostreptococcus prevotii| 50|| Proteus mirabilis| 6.25|| Proteus morganii| 1.56|| Proteus rettgeri| 1.56|| Proteus spp.| 1.57 - 2.25|| Proteus vulgaris| 1.56|| Pseudomonas aeruginosa| 3.13 - 50|| Salmonella Enteritidis| 1.56|| Salmonella Paratyphi| 0.78|| Salmonella schottmulleri| 0.78|| Salmonella typhimurium| 1.56|| Serratia marcescens| 1.56 - 3.13|| Staphylococcus asaccharolyticus| 25|| Staphylococcus aureus| 6.25 - 50|| Streptococcus intermedius| 200|| Streptococcus pyogenes| 61 - >100|| Veillonella parvula | 25|| |
