pyrazinamide

Pyrazinamide is a pyrazine that is used therapeutically as an antitubercular agent.Target: AntibacterialPyrazinamide is a prodrug that stops the growth of Mycobacterium tuberculosis. Pyrazinoic acid was thought to inhibit the enzyme fatty acid synthase (FAS) I, which is required by the bacterium to synthesise fatty acids although this has been discounted. It was also suggested that the accumulation of pyrazinoic acid disrupts membrane potential and interferes with energy production, necessary for survival of M. tuberculosis at an acidic site of infection. Pyrazinoic acid binds to the ribosomal protein S1 (RpsA) and inhibits trans-translation. This may explain the ability of the drug to kill dormant mycobacteria [1-4].

Signaling Pathways >> Autophagy >> Autophagy

Signaling Pathways >> Anti-infection >> Bacterial

Research Areas >> Infection

[1]. Zhang, Y. and D. Mitchison, The curious characteristics of pyrazinamide: a review. Int J Tuberc Lung Dis, 2003. 7(1): p. 6-21.

[2]. Zimhony, O., et al., Pyrazinamide inhibits the eukaryotic-like fatty acid synthetase I (FASI) of Mycobacterium tuberculosis. Nat Med, 2000. 6(9): p. 1043-7.

[3]. Boshoff, H.I., V. Mizrahi, and C.E. Barry, 3rd, Effects of pyrazinamide on fatty acid synthesis by whole mycobacterial cells and purified fatty acid synthase I. J Bacteriol, 2002. 184(8): p. 2167-72.

[4]. Shi, W., et al., Pyrazinamide inhibits trans-translation in Mycobacterium tuberculosis. Science, 2011. 333(6049): p. 1630-2.

Puromycin 2HCl | Geneticin | Tunicamycin | Hygromycin B | Salinomycin | Avibactam sodium | Neomycin sulfate | Vaborbactam | Methicillin SodiuM | Rifampicin | Metronidazole | Carbenicillin disodium | Ceftazidime | Eravacycline dihydrochloride | cefotaxime sodium

DATA ITEMS CITED :

16

MOLECULAR FORMULA :

C5-H5-N3-O

MOLECULAR WEIGHT :

123.13

WISWESSER LINE NOTATION :

T6N DNJ BVZ

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Human - woman

DOSE/DURATION :

10 mg/kg

TOXIC EFFECTS :

Vascular - BP elevation not characterized in autonomic section

TYPE OF TEST :

LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

3 gm/kg

TOXIC EFFECTS :

Behavioral - excitement Behavioral - ataxia

TYPE OF TEST :

LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

3 gm/kg

TOXIC EFFECTS :

Behavioral - excitement Behavioral - ataxia

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intraperitoneal

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

1680 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Subcutaneous

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

2973 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Mammal - dog

DOSE/DURATION :

90 gm/kg/90D-I

TOXIC EFFECTS :

Liver - hepatitis (hepatocellular necrosis), zonal

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

328 gm/kg/78W-C

TOXIC EFFECTS :

Tumorigenic - equivocal tumorigenic agent by RTECS criteria Blood - lymphoma, including Hodgkin's disease

TYPE OF TEST :

TD - Toxic dose (other than lowest)

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

756 gm/kg/30W-C

TOXIC EFFECTS :

Tumorigenic - equivocal tumorigenic agent by RTECS criteria Lungs, Thorax, or Respiration - tumors

TYPE OF TEST :

Mutation test systems - not otherwise specified

TYPE OF TEST :

Cytogenetic analysis

MUTATION DATA

TEST SYSTEM :

Rodent - mouse

DOSE/DURATION :

500 mg/kg

REFERENCE :

MUREAV Mutation Research. (Elsevier Science Pub. B.V., POB 211, 1000 AE Amsterdam, Netherlands) V.1- 1964- Volume(issue)/page/year: 321,1,1994 *** NIOSH STANDARDS DEVELOPMENT AND SURVEILLANCE DATA *** NIOSH OCCUPATIONAL EXPOSURE SURVEY DATA : NOES - National Occupational Exposure Survey (1983) NOES Hazard Code - X6080 No. of Facilities: 7 (estimated) No. of Industries: 1 No. of Occupations: 2 No. of Employees: 307 (estimated) No. of Female Employees: 251 (estimated)