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Details

Stereochemistry ACHIRAL
Molecular Formula C12H12N4O3
Molecular Weight 260.2487
Optical Activity UNSPECIFIED
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of BENZNIDAZOLE

SMILES

[O-][N+](=O)C1=NC=CN1CC(=O)NCC2=CC=CC=C2

InChI

InChIKey=CULUWZNBISUWAS-UHFFFAOYSA-N
InChI=1S/C12H12N4O3/c17-11(14-8-10-4-2-1-3-5-10)9-15-7-6-13-12(15)16(18)19/h1-7H,8-9H2,(H,14,17)

HIDE SMILES / InChI

Molecular Formula C12H12N4O3
Molecular Weight 260.2487
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Description

Benznidazole is an antiparasitic medication used in first-line treatment of Chagas disease. Benznidazole is a nitroimidazole antiparasitic with good activity against acute infection with Trypanosoma cruzi, commonly referred to as Chagas disease. Like other nitroimidazoles, benznidazole's main mechanism of action is to generate radical species which can damage the parasite's DNA or cellular machinery. Under anaerobic conditions, the nitro group of nitroimidazoles is believed to be reduced by the pyruvate:ferredoxin oxidoreductase complex to create a reactive nitro radical species. The nitro radical can then either engage in other redox reactions directly or spontaneously give rise to a nitrite ion and imidazole radical instead. In mammals, the principal mediators of electron transport are NAD+/NADH and NADP+/NADPH, which have a more positive reduction potential and so will not reduce nitroimidazoles to the radical form. This limits the spectrum of activity of nitroimidazoles so that host cells and DNA are not also damaged. This mechanism has been well-established for 5-nitroimidazoles such as metronidazole, but it is unclear if the same mechanism can be expanded to 2-nitroimidazoles (including benznidazole). In the presence of oxygen, by contrast, any radical nitro compounds produced will be rapidly oxidized by molecular oxygen, yielding the original nitroimidazole compound and a superoxide anion in a process known as "futile cycling". In these cases, the generation of superoxide is believed to give rise to other reactive oxygen species. The degree of toxicity or mutagenicity produced by these oxygen radicals depends on cells' ability to detoxify superoxide radicals and other reactive oxygen species. In mammals, these radicals can be converted safely to hydrogen peroxide, meaning benznidazole has very limited direct toxicity to human cells. In Trypanosoma species, however, there is a reduced capacity to detoxify these radicals, which results in damage to the parasite's cellular machinery. Benznidazole has a significant activity during the acute phase of Chagas disease, with a therapeutical success rate up to 80%. Its curative capabilities during the chronic phase are, however, limited. Some studies have found parasitologic cure (a complete elimination of T. cruzi from the body) in pediatric and young patients during the early stage of the chronic phase, but overall failure rate in chronically infected individuals is typically above 80%. However, some studies indicate treatment with benznidazole during the chronic phase, even if incapable of producing parasitologic cure, because it reduces electrocardiographic changes and a delays worsening of the clinical condition of the patient. Side effects tend to be common and occur more frequently with increased age. The most common adverse reactions associated with benznidazole are allergic dermatitis and peripheral neuropathy. It is reported that up to 30% of people will experience dermatitis when starting treatment. Benznidazole may cause photosensitization of the skin, resulting in rashes. Rashes usually appear within the first 2 weeks of treatment and resolve over time. In rare instances, skin hypersensitivity can result in exfoliative skin eruptions, edema, and fever. Peripheral neuropathy may occur later on in the treatment course and is dose-dependent. Other adverse reactions include anorexia, weight loss, nausea, vomiting, insomnia, and dyslexia, and bone marrow suppression. Gastrointestinal symptoms usually occur during the initial stages of treatment and resolves over time. Bone marrow suppression has been linked to the cumulative dose exposure.

CNS Activity

Originator

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Rochagan
PubMed

PubMed

TitleDatePubMed
Trypanocidal activity of 4 isopropyl salicylaldehyde and 4-isopropyl salicylic acid on Trypanosoma cruzi.
2001 Jan-Mar
[Implementation and evaluation of a locally sustainable system of prenatal diagnosis to detect cases of congenital Chagas disease in endemic areas of Paraguay].
2005
[Treatment of Chagas disease with benznidazole and thioctic acid].
2005
Benznidazole vs benznidazole in multilamellar liposomes: how different they interact with blood components?
2005 Apr
Trypanocidal activity of N-isopropyl oxamate on cultured epimastigotes and murine trypanosomiasis using different Trypanosoma cruzi strains.
2005 Apr
Molecular diagnosis and typing of Trypanosoma cruzi populations and lineages in cerebral Chagas disease in a patient with AIDS.
2005 Dec
The trypanocidal effect of sesquiterpene lactones helenalin and mexicanin on cultured epimastigotes.
2005 Feb
Chagas disease in bone marrow transplantation: an approach to preemptive therapy.
2005 Jul
Amino acid metabolic routes in Trypanosoma cruzi: possible therapeutic targets against Chagas' disease.
2005 Mar
Response to chemotherapy with benznidazole of clones isolated from the 21SF strain of Trypanosoma cruzi (biodeme Type II, Trypanosoma cruzi II).
2005 Mar-Apr
Benznidazole-induced genotoxicity in diploid cells of Aspergillus nidulans.
2005 May
Trypanosoma cruzi: chemotherapeutic effects of clomipramine in mice infected with an isolate obtained from an endemic area.
2005 Oct
[Clinical predictors of chronic chagasic myocarditis progression].
2005 Sep
Transmission of T. cruzi infection via liver transplantation to a nonreactive recipient for Chagas' disease.
2005 Sep
Diterpenoid alkaloid derivatives as potential chemotherapeutic agents in American trypanosomiasis.
2006
Treatment of experimental chronic chagas disease with trifluralin.
2006 Apr
Deletion of copies of the gene encoding old yellow enzyme (TcOYE), a NAD(P)H flavin oxidoreductase, associates with in vitro-induced benznidazole resistance in Trypanosoma cruzi.
2006 Apr
Toxic side effects of drugs used to treat Chagas' disease (American trypanosomiasis).
2006 Aug
Improving anti-trypanosomal activity of 3-aminoquinoxaline-2-carbonitrile N1,N4-dioxide derivatives by complexation with vanadium.
2006 Aug 15
Synthesis and leishmanicidal activities of 1-(4-X-phenyl)-N'-[(4-Y-phenyl)methylene]-1H-pyrazole-4-carbohydrazides.
2006 Jan
Development of parenteral formulations and evaluation of the biological activity of the trypanocide drug benznidazole.
2006 Jan 13
Development of resazurin microtiter assay for drug sensibility testing of Trypanosoma cruzi epimastigotes.
2006 Jul
The thymus is a common target organ in infectious diseases.
2006 Jun
2H-benzimidazole 1,3-dioxide derivatives: a new family of water-soluble anti-trypanosomatid agents.
2006 Jun 1
Long-term cardiac outcomes of treating chronic Chagas disease with benznidazole versus no treatment: a nonrandomized trial.
2006 May 16
Summaries for patients. Long-term outcomes of treating nonacute Chagas disease with benznidazole.
2006 May 16
Increased expression of iron-containing superoxide dismutase-A (TcFeSOD-A) enzyme in Trypanosoma cruzi population with in vitro-induced resistance to benznidazole.
2006 Nov
In vitro antiprotozoal activity of the lipophilic extracts of different parts of Turkish Pistacia vera L.
2006 Nov
Benznidazole treatment during early-indeterminate Chagas' disease shifted the cytokine expression by innate and adaptive immunity cells toward a type 1-modulated immune profile.
2006 Nov
Trypanosoma cruzi: alteration in the lymphoid compartments following interruption of infection by early acute benznidazole therapy in mice.
2006 Nov
Activity of neolignans isolated from Piper regnellii (MIQ.) C. DC. var. pallescens (C. DC.) YUNCK against Trypanosoma cruzi.
2006 Oct
Polymerase chain reaction detection and serologic follow-up after treatment with benznidazole in Bolivian children infected with a natural mixture of Trypanosoma cruzi I and II.
2006 Sep
Noncommunicable diseases and injuries in Latin America and the Caribbean: time for action.
2006 Sep
Detection of parasitemia profiles by blood culture after treatment of human chronic Trypanosoma cruzi infection.
2006 Sep
Novel potential drug against T. cruzi and its interaction with surfactant micelles.
2007
In vitro and in vivo trypanocidal activity of the ethyl esters of N-allyl and N-propyl oxamates using different Trypanosoma cruzi strains.
2007 Apr
The Anti-Trypanosoma cruzi activity of posaconazole in a murine model of acute Chagas' disease is less dependent on gamma interferon than that of benznidazole.
2007 Apr
Mode of action of natural and synthetic drugs against Trypanosoma cruzi and their interaction with the mammalian host.
2007 Apr
Synthesis, in vitro evaluation, and SAR studies of a potential antichagasic 1H-pyrazolo[3,4-b]pyridine series.
2007 Jan 1
Effects of canthin-6-one alkaloids from Zanthoxylum chiloperone on Trypanosoma cruzi-infected mice.
2007 Jan 19
Trypanocide treatment among adults with chronic Chagas disease living in Santa Fe city (Argentina), over a mean follow-up of 21 years: parasitological, serological and clinical evolution.
2007 Jan-Feb
DNA damage and nitric oxide synthesis in experimentally infected Balb/c mice with Trypanosoma cruzi.
2007 Jul
Chagas' disease reactivation with skin symptoms in a patient with kidney transplant.
2007 Jun
Usefulness of PCR strategies for early diagnosis of Chagas' disease reactivation and treatment follow-up in heart transplantation.
2007 Jun
Treatment with benznidazole or thioridazine in the chronic phase of experimental Chagas disease improves cardiopathy.
2007 Jun
Liver transplantation from deceased donors serologically positive for Chagas disease.
2007 Mar
In vitro and in vivo activity of lignan lactones derivatives against Trypanosoma cruzi.
2007 Mar
Allopurinol is effective to modify the evolution of Trypanosoma cruzi infection in mice.
2007 Oct
Synthesis, Cruzain docking, and in vitro studies of aryl-4-oxothiazolylhydrazones against Trypanosoma cruzi.
2007 Sep
Trypanosoma cruzi: characterisation of the gene encoding tyrosine aminotransferase in benznidazole-resistant and susceptible populations.
2008 Jan
Patents

Patents

Sample Use Guides

In Vivo Use Guide
Adults and children 12 years of age and over—Dose is based on body weight. The usual dose is 5 to 7 milligrams (mg) per kilogram (kg) (2.2 to 3.1 mg per pound) of body weight per day. Treatment should continue for thirty to sixty days.
Route of Administration: Oral
In Vitro Use Guide
RAW 264.7 cells (murine macrophages, ATCC number CRL-2922) were cultured at a density of 250,000 cells/cm2, in RPMI 1640 medium supplemented with 5% fetal bovine serum, in a humidified atmosphere with 5% CO2 at 37 _C. RAWcells were infected with T. cruzi trypomastigotes (Y strain) at a 3:1 ratio (trypomastigote: RAW cell). Trypomastigotes were allowed to infect cells for 24 h, after which the supernatant was removed and the medium was replaced with fresh medium with the respective treatments. After 48 h of treatment, cells were harvested by scraping, and DNA was isolated using the Wizard Genomic DNA Purification Kit (Promega, USA), following the manufacturer's instructions. BNZ (Benznidazole) showed a concentration-dependent effect, decreasing the parasite load by 40, 60 and 90% at 1, 2 or 10 mkM, respectively.
Substance Class Chemical
Created
by admin
on Mon Oct 21 21:27:33 UTC 2019
Edited
by admin
on Mon Oct 21 21:27:33 UTC 2019
Record UNII
YC42NRJ1ZD
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
BENZNIDAZOLE
INN   MART.   MI   USAN   WHO-DD   WHO-IP  
USAN   INN  
Official Name English
BENZNIDAZOLE [INN]
Common Name English
BENZONIDAZOL
Common Name English
ROCHAGAN
Brand Name English
RO-7-1051
Code English
NSC-299972
Code English
BENZNIDAZOLE [WHO-IP]
Common Name English
BENZNIDAZOLE [USAN]
Common Name English
BENZNIDAZOLE [MART.]
Common Name English
IMIDAZOLE-1-ACETAMIDE, N-BENZYL-2-NITRO-
Systematic Name English
RO 07-1051
Code English
1H-IMIDAZOLE-1-ACETAMIDE, 2-NITRO-N-(PHENYLMETHYL)-
Systematic Name English
BENZNIDAZOLUM [WHO-IP LATIN]
Common Name English
BENZNIDAZOLE [WHO-DD]
Common Name English
BENZNIDAZOLE [MI]
Common Name English
RO-07-1051
Code English
N-BENZYL-2-NITROIMIDAZOLE-1-ACETAMIDE
Systematic Name English
RADANIL
Brand Name English
Classification Tree Code System Code
WHO-ESSENTIAL MEDICINES LIST 6.5.5.2
Created by admin on Mon Oct 21 21:27:33 UTC 2019 , Edited by admin on Mon Oct 21 21:27:33 UTC 2019
NCI_THESAURUS C277
Created by admin on Mon Oct 21 21:27:33 UTC 2019 , Edited by admin on Mon Oct 21 21:27:33 UTC 2019
FDA ORPHAN DRUG 425214
Created by admin on Mon Oct 21 21:27:33 UTC 2019 , Edited by admin on Mon Oct 21 21:27:33 UTC 2019
WHO-ATC P01CA02
Created by admin on Mon Oct 21 21:27:33 UTC 2019 , Edited by admin on Mon Oct 21 21:27:33 UTC 2019
Code System Code Type Description
EVMPD
SUB05753MIG
Created by admin on Mon Oct 21 21:27:33 UTC 2019 , Edited by admin on Mon Oct 21 21:27:33 UTC 2019
PRIMARY
LactMed
22994-85-0
Created by admin on Mon Oct 21 21:27:33 UTC 2019 , Edited by admin on Mon Oct 21 21:27:33 UTC 2019
PRIMARY
PUBCHEM
31593
Created by admin on Mon Oct 21 21:27:33 UTC 2019 , Edited by admin on Mon Oct 21 21:27:33 UTC 2019
PRIMARY
NCI_THESAURUS
C1013
Created by admin on Mon Oct 21 21:27:33 UTC 2019 , Edited by admin on Mon Oct 21 21:27:33 UTC 2019
PRIMARY
ChEMBL
CHEMBL110
Created by admin on Mon Oct 21 21:27:33 UTC 2019 , Edited by admin on Mon Oct 21 21:27:33 UTC 2019
PRIMARY
WHO INTERNATIONAL PHARMACOPEIA
BENZNIDAZOLE
Created by admin on Mon Oct 21 21:27:33 UTC 2019 , Edited by admin on Mon Oct 21 21:27:33 UTC 2019
PRIMARY Description: A yellowish powder; odourless or almost odourless. Solubility: Practically insoluble in water; sparingly soluble in acetone R; slightly soluble in methanol R; very slightly soluble in ethanol (~750 g/l) TS. Category: Antiprotozoal drug. Storage: Benznidazole should be kept in a well-closed container, protected from light. Requirement: Benznidazole contains not less than 98.5% and not more than the equivalent of 101.5% of C12H12N4O3, calculated with reference to the dried substance.
RXCUI
18994
Created by admin on Mon Oct 21 21:27:33 UTC 2019 , Edited by admin on Mon Oct 21 21:27:33 UTC 2019
PRIMARY RxNorm
EPA CompTox
22994-85-0
Created by admin on Mon Oct 21 21:27:33 UTC 2019 , Edited by admin on Mon Oct 21 21:27:33 UTC 2019
PRIMARY
INN
3541
Created by admin on Mon Oct 21 21:27:33 UTC 2019 , Edited by admin on Mon Oct 21 21:27:33 UTC 2019
PRIMARY
WIKIPEDIA
BENZNIDAZOLE
Created by admin on Mon Oct 21 21:27:33 UTC 2019 , Edited by admin on Mon Oct 21 21:27:33 UTC 2019
PRIMARY
CAS
22994-85-0
Created by admin on Mon Oct 21 21:27:33 UTC 2019 , Edited by admin on Mon Oct 21 21:27:33 UTC 2019
PRIMARY
MERCK INDEX
M2356
Created by admin on Mon Oct 21 21:27:33 UTC 2019 , Edited by admin on Mon Oct 21 21:27:33 UTC 2019
PRIMARY Merck Index
MESH
C009999
Created by admin on Mon Oct 21 21:27:33 UTC 2019 , Edited by admin on Mon Oct 21 21:27:33 UTC 2019
PRIMARY
Related Record Type Details
TRANSPORTER -> INHIBITOR
IC50
BINDER->LIGAND
BINDING
TARGET -> INHIBITOR
EXCRETED UNCHANGED
TRANSPORTER -> SUBSTRATE
Related Record Type Details
ACTIVE MOIETY
http://apps.who.int/phint/pdf/b/Jb.6.1.47.pdf
Name Property Type Amount Referenced Substance Defining Parameters References
CSF/PLASMA RATIO PHARMACOKINETIC
Tmax PHARMACOKINETIC
Biological Half-life PHARMACOKINETIC ELIMINATION
PHARMACOKINETIC