Description
Benznidazole is the second of the drugs approved for treatment of Chagas' disease. Like
nifurtimox, it is effective against the circulating form of Trypanosoma cruzi during the acute phase
of the disease, but also like nifurtimox, it is ineffective during the chronic stage of the disease.
Description
Benznidazole is an orally bioavailable antiprotozoal agent. It is a 2-nitroimidazole prodrug that becomes active when the nitro group is reduced within the parasite. It inhibits the growth of the parasites
T. cruzi,
T. vaginalis,
G. lamblia, and
E. histolytica (IC
50s = 8.1, 18.62, 22.58, and 4.27 μM, respectively). It also inhibits clonogenic growth of human C33A cervical and KNS42 glioblastoma cancer cells under hypoxic, but not normoxic, conditions when used at a concentration of 100 μM. Benznidazole (100 mg/kg per day) decreases
T. cruzi blood parasitemia to below detectable levels in a mouse model of chronic stable Chagas disease. Formulations containing benznidazole have been used in the treatment of Chagas disease caused by
T. cruzi.
Uses
Benznidazole (BNZ) is traditionally used to treat Chagas disease caused by Trypanosoma cruzi. The drugs used for the treatment of this disease, Nifurtimox and Benznidazole, are toxic and present sever
e side effects.
Uses
N-Benzyl-2-nitro-1
H-imidazole-1-acetamide (Benznidazole) may be used as reference drug for the extraction of guaianolide from the aerial parts of
Tanacetum parthenium and to evaluate its
in vitro antiprotozoal activity.
Definition
ChEBI: A monocarboxylic acid amide obtained by formal condensation of the carboxy group of (2-nitroimidazol-1-yl)acetic acid with the aromatic amino group of benzylamine. Used for treatment of Chagas disease.
Antimicrobial activity
It exhibits antiprotozoal activity, particularly against Trypanosoma cruzi.
General Description
N-Benzyl-2-nitro-1
H-imidazole-1-acetamide (Benznidazole) is a nitro-heterocyclic compound. It is widely employed drug for the treatment of Chagas disease. It exhibits three polymorphic forms..
Pharmaceutical Applications
A synthetic 2-nitroimidazole, formulated for oral administration. Solubility in water 400 mg/L.
Mechanism of action
Studies suggest that benznidazole does not catalyze the formation of ROS and, therefore, has a
mechanism of action different from that of nifurtimox. It has been proposed that benznidazole
undergoes an one-electron transfer to the nitro group, which in turn dismutates to give back the
nitroimidazole and a nitrosoimidazole. The latter product may then undergo an electrophilic
addition to trypanothione, which leads to depletion of trypanothione, an essential enzyme system
in the Trypanosoma cruzi.
Pharmacokinetics
Oral bioavailability :High
Cmax 100 mg oral ：2.2–2.8 mg/L after 3–4 h
Plasma half-life：10.5–13.6 h
Volume of distribution：c. 0.56 L/kg
Plasma protein binding： c. 44%
The 2-nitro group undergoes reduction to the amine and hydrolysis to the hydroxy derivative.
Clinical Use
N-Benzyl-2-nitroimidazole-1-acetamide (Radanil, Rochagan)is a nitroimidazole derivative that is used for the treatment ofChagas disease. It is not available in the United States but isused extensively in South America. The effectiveness of benznidazoleis similar to that of nifurtimox. Therapy forAmerican trypanosomiasis with oral benznidazole requiresseveral weeks and is frequently accompanied by adverse effectssuch as peripheral neuropathy, bone marrow depression,and allergic-type reactions.
Clinical Use
Benznidazole is used in treatment of South American trypanosomiasis (Chagas disease).
Side effects
Adverse effects are more common in the elderly and include nausea, vomiting, abdominal pain, peripheral neuropathy and severe skin reactions.
References
[1] SHILPI KHARE. Antitrypanosomal Treatment with Benznidazole Is Superior to Posaconazole Regimens in Mouse Models of Chagas Disease.[J]. Antimicrobial Agents and Chemotherapy, 2015: 6385-6394. DOI:
10.1128/aac.00689-15[2] ANDREA TROCHINE. Benznidazole biotransformation and multiple targets in Trypanosoma cruzi revealed by metabolomics.[J]. PLoS Neglected Tropical Diseases, 2014, 8 5: e2844. DOI:
10.1371/journal.pntd.0002844[3] JULIANA COGO . Trypanocidal activity of guaianolide obtained from Tanacetum parthenium (L.) Schultz-Bip. and its combinational effect with benznidazole[J]. Phytomedicine, 2012, 20 1: Pages 59-66. DOI:
10.1016/j.phymed.2012.09.011[4] EMANUEL HERNáNDEZ-NúEZ. Design, Synthesis and Biological Evaluation of 2-(2-Amino-5(6)-nitro-1H-benzimidazol-1-yl)-N-arylacetamides as Antiprotozoal Agents.[J]. Molecules, 2017. DOI:
10.3390/molecules22040579[5] QUHUAN LI Z Y Q Lin. Hypoxia-activated cytotoxicity of benznidazole against clonogenic tumor cells[J]. Cancer Biology & Therapy, 2016, 17 1: 1266-1273. DOI:
10.1080/15384047.2016.1250988
