{{chembox | Verifiedfields = changed | Watchedfields = changed | verifiedrevid = 464376650 | ImageFileL1_Ref = {{chemboximage|correct|??}} | ImageFileL1 = Pyrazinoic acid.png | ImageSizeL1 = 120px | ImageAltL1 = Skeletal formula of pyrazinoic acid | ImageFileR1 = Pyrazinoic acid 3D spacefill.png | ImageSizeR1 = 130 | ImageAltR1 = Space-filling model of the pyrazinoic acid molecule | PIN = Pyrazine-2-carboxylic acid | OtherNames = |Section1={{Chembox Identifiers | InChI = 1/C5H4N2O2/c8-5(9)4-3-6-1-2-7-4/h1-3H,(H,8,9) | InChIKey = NIPZZXUFJPQHNH-UHFFFAOYAS | ChEMBL_Ref = {{ebicite|correct|EBI}} | ChEMBL = 613 | StdInChI_Ref = {{stdinchicite|correct|chemspider}} | StdInChI = 1S/C5H4N2O2/c8-5(9)4-3-6-1-2-7-4/h1-3H,(H,8,9) | StdInChIKey_Ref = {{stdinchicite|correct|chemspider}} | StdInChIKey = NIPZZXUFJPQHNH-UHFFFAOYSA-N | CASNo_Ref = {{cascite|correct|CAS}} | CASNo = 98-97-5 | UNII_Ref = {{fdacite|correct|FDA}} | UNII = 2WB23298SP | ChEBI_Ref = {{ebicite|changed|EBI}} | ChEBI = 71311 | PubChem = 1047 | ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} | ChemSpiderID = 1018 | SMILES = O=C(O)c1nccnc1 | MeSHName = Pyrazinoic+acid }} |Section2={{Chembox Properties | Formula =C<sub>5</sub>H<sub>4</sub>N<sub>2</sub>O<sub>2</sub> | MolarMass =124.10 g/mol | Appearance =white to off white crystalline powder | Density = 1.403g/cm<sup>3</sup> | MeltingPtC = 222 to 225 | MeltingPt_notes = | BoilingPtC = 313.1 | BoilingPt_notes = at 760 mmHg | Solubility =soluble in cold water | pKa = 2.9 }} |Section3={{Chembox Hazards | MainHazards = | FlashPtC = 143.1 | AutoignitionPtC = }} }}
'''Pyrazinoic acid''' (POA) is a pyrazinamide (PZA) metabolite. ''Mycobacterium tuberculosis'' pyrazinamidase converts pyrazinamide into this compound, the active form of pyrazinamide.<ref name="Njire et al 2017">{{cite journal |last1=Njire |first1=Moses |last2=Wang |first2=Na |last3=Wang |first3=Bangxing |last4=Tan |first4=Yaoju |last5=Cai |first5=Xingshan |last6=Liu |first6=Yanwen |last7=Mugweru |first7=Julius |last8=Guo |first8=Jintao |last9=Hameed |first9=H. M. Adnan |last10=Tan |first10=Shouyong |last11=Liu |first11=Jianxiong |last12=Yew |first12=Wing Wai |last13=Nuermberger |first13=Eric |last14=Lamichhane |first14=Gyanu |last15=Liu |first15=Jinsong |last16=Zhang |first16=Tianyu |title=Pyrazinoic acid inhibits a bifunctional enzyme in ''Mycobacterium tuberculosis'' |journal=Antimicrobial Agents and Chemotherapy |date=1 July 2017 |volume=61 |issue=7 |doi=10.1128/AAC.00070-17 |pmid=28438933 |pmc=5487608 |doi-access=free }}</ref> The cognate anion is called '''pyrazinoate'''.<ref name=Fernandes/>
It inhibits ''panD'', the aspartate 1-decarboxylase.<ref>{{cite journal |last1=Sun |first1=Qingan |last2=Li |first2=Xiaojun |last3=Perez |first3=Lisa M. |last4=Shi |first4=Wanliang |last5=Zhang |first5=Ying |last6=Sacchettini |first6=James C. |title=The molecular basis of pyrazinamide activity on Mycobacterium tuberculosis PanD |journal=Nature Communications |date=17 January 2020 |volume=11 |issue=1 |doi=10.1038/s41467-019-14238-3}}</ref> It also inhibits ''Rv2783'' (''gpsI''), a polyribonucleotide nucleotidyltransferase and guanosine pentaphosphate synthetase.<ref name="Njire et al 2017"/>
==Role in tuberculosis treatment== One way ''M. tuberculosis'' becomes resistant to PZA is by disabling the pyrazinamidase by through mutations.<ref name="Njire et al 2017"/> Using another chemical precursor to POA could bypass this problem.<ref name=Fernandes/> (POA cannot be directly used because it is not lipophilic enough to cross the bacterial cell membrane at physiological pH, being mostly ionized.)<ref name=Fernandes/>
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.<ref name=Fernandes>{{cite journal |last1=Fernandes |first1=João Paulo-dos Santos |last2=Pavan |first2=Fernando Rogerio |last3=Leite |first3=Clarice Queico Fujimura |last4=Felli |first4=Veni Maria Andres |title=Synthesis and evaluation of a pyrazinoic acid prodrug in Mycobacterium tuberculosis |journal=Saudi Pharmaceutical Journal |date=2014 |volume=22 |issue=4 |pages=376–380 |doi=10.1016/j.jsps.2013.12.005 |pmid=25161383 |pmc=4142361 }}</ref>
==References== {{reflist}}
Category:Pyrazines Category:Aromatic acids
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