Pyrazinoic acid
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| Names | |||
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| Preferred IUPAC name
Pyrazine-2-carboxylic acid | |||
| Identifiers | |||
3D model (JSmol) |
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| ChEBI | |||
| ChEMBL | |||
| ChemSpider | |||
| ECHA InfoCard | 100.002.471 | ||
| MeSH | Pyrazinoic+acid | ||
PubChem CID |
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| UNII | |||
CompTox Dashboard (EPA) |
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| Properties | |||
| C5H4N2O2 | |||
| Molar mass | 124.10 g/mol | ||
| Appearance | white to off white crystalline powder | ||
| Density | 1.403g/cm3 | ||
| Melting point | 222 to 225 °C (432 to 437 °F; 495 to 498 K) | ||
| Boiling point | 313.1 °C (595.6 °F; 586.2 K) at 760 mmHg | ||
| soluble in cold water | |||
| Acidity (pKa) | 2.9 | ||
| Hazards | |||
| Flash point | 143.1 °C (289.6 °F; 416.2 K) | ||
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
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Pyrazinoic acid (POA) is a pyrazinamide (PZA) metabolite. Mycobacterium tuberculosis pyrazinamidase converts pyrazinamide into this compound, the active form of pyrazinamide.[1] The cognate anion is called pyrazinoate.[2]
It inhibits panD, the aspartate 1-decarboxylase.[3] It also inhibits Rv2783 (gpsI), a polyribonucleotide nucleotidyltransferase and guanosine pentaphosphate synthetase.[1]
Role in tuberculosis treatment
[edit]One way M. tuberculosis becomes resistant to PZA is by disabling the pyrazinamidase by through mutations.[1] Using another chemical precursor to POA could bypass this problem.[2] (POA cannot be directly used because it is not lipophilic enough to cross the bacterial cell membrane at physiological pH, being mostly ionized.)[2]
One group of proposed alternative prodrugs is the esters of POA (pyrazinoate esters). It has been shown in vitro that their MICs are lower than PZA, meaning they are more potent antibiotics. Moreover, they cross the bacterial membrane more easily, due to their higher lipophilicity.[2]
References
[edit]- 1 2 3 Njire, Moses; Wang, Na; Wang, Bangxing; Tan, Yaoju; Cai, Xingshan; Liu, Yanwen; Mugweru, Julius; Guo, Jintao; Hameed, H. M. Adnan; Tan, Shouyong; Liu, Jianxiong; Yew, Wing Wai; Nuermberger, Eric; Lamichhane, Gyanu; Liu, Jinsong; Zhang, Tianyu (1 July 2017). "Pyrazinoic acid inhibits a bifunctional enzyme in Mycobacterium tuberculosis". Antimicrobial Agents and Chemotherapy. 61 (7). doi:10.1128/AAC.00070-17. PMC 5487608. PMID 28438933.
- 1 2 3 4 Fernandes, João Paulo-dos Santos; Pavan, Fernando Rogerio; Leite, Clarice Queico Fujimura; Felli, Veni Maria Andres (2014). "Synthesis and evaluation of a pyrazinoic acid prodrug in Mycobacterium tuberculosis". Saudi Pharmaceutical Journal. 22 (4): 376–380. doi:10.1016/j.jsps.2013.12.005. PMC 4142361. PMID 25161383.
- ↑ Sun, Qingan; Li, Xiaojun; Perez, Lisa M.; Shi, Wanliang; Zhang, Ying; Sacchettini, James C. (17 January 2020). "The molecular basis of pyrazinamide activity on Mycobacterium tuberculosis PanD". Nature Communications. 11 (1). doi:10.1038/s41467-019-14238-3. PMC 6969166.
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