| Stereochemistry | RACEMIC |
| Molecular Formula | C10H13N3O5S |
| Molecular Weight | 287.292 |
| Optical Activity | ( + / - ) |
| Defined Stereocenters | 0 / 1 |
| E/Z Centers | 1 |
| Charge | 0 |
SHOW SMILES / InChI
SMILES
CC1CS(=O)(=O)CCN1\N=C\C2=CC=C(O2)[N+]([O-])=O
InChI
InChIKey=ARFHIAQFJWUCFH-IZZDOVSWSA-N
InChI=1S/C10H13N3O5S/c1-8-7-19(16,17)5-4-12(8)11-6-9-2-3-10(18-9)13(14)15/h2-3,6,8H,4-5,7H2,1H3/b11-6+
Nifurtimox is a nitrofuran derivative used as a primary agent in the treatment of American trypanosomiasis (Chagas' disease) caused by Trypanosoma cruzi, especially in the acute, early stage of the disease. The efficacy of nifurtimox in the treatment of chronic Chagas' disease varies from one country to another, possibly due to variation in the sensitivity of different strains of the organism. Nifurtimox has also been used to treat African trypanosomiasis (sleeping sickness) and is active in the second stage of the disease (central nervous system involvement). When nifurtimox is given on its own, about half of all patients will relapse, but the combination of melarsoprol with nifurtimox appears to be efficacious. Nifurtimox forms a nitro-anion radical metabolite that reacts with nucleic acids of the parasite causing significant break down of DNA. Nifurtimox undergoes reduction and creates oxygen radicals such as superoxide. These radicals are toxic to T. cruzi. Mammalian cells are protected by the presence of catalase, glutathione, peroxidases, and superoxide dismutase. Accumulation of hydrogen peroxide to cytotoxic levels results in parasite death. Side effects occur following chronic administration, particularly in elderly people. Major toxicities include immediate hypersensitivities such as anaphylaxis and delayed hypersensitivity reaction involving icterus and dermatitis. Central nervous system disturbances and peripheral neuropathy may also occur.
CNS Activity
Originator
Approval Year
Doses
AEs
Overview
| CYP3A4 | CYP2C9 | CYP2D6 | hERG |
|---|---|---|---|
OverviewOther
Drug as perpetrator
Drug as victim
Tox targets
PubMed
Patents
Sample Use Guides
For acute and chronic infections: Oral, 8 to 10 mg per kg of body weight per day in three or four divided doses after meals, for ninety to one hundred twenty days.
Route of Administration:
Oral
Neural tumor cell lines (U-87, U373, CHLA-02-ATRT and PFSK-1), medulloblastoma cell lines (Daoy and D283) and TC-71, 143B, MG-63, MMH-ES, RD-ES, SK-ES-1 and SK-N-MC cell lines were used for activity evaluation. The viability of cells exposed to nifurtimox and BSO was determined using a modified methyl tetrazolium (MTT; Sigma) assay. 0.5–1.0 × 10^4 cells/well of exponentially growing cells were plated in 96-well plates. 24 hours later, nifurtimox or BSO was added to each well at concentrations up to 200mkM. After 72, 96, or 120 hours of continuous drug exposure, 15 μL of 5 mg/ml MTT was added to each well and the plates were incubated for 4 hours at 37 °C. Medium was replaced with 150 μL of DMSO and the optical density (OD) was measured at 550 nm using a microplate spectrophotometer (Anthos Analytical, Durham, NC). Cell numbers were estimated from OD measurements in individual wells. Relative cell viability was calculated by subtracting the background OD of media alone and then dividing by the OD of control wells.
ACTIVE MOIETY
