Structure of Benznidazole
CAS No.: 22994-85-0
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The BI-3802 was designed by Boehringer Ingelheim and could be obtained free of charge through the Boehringer Ingelheim open innovation portal opnMe.com, associated with its negative control.
Benznidazole is an antiparasitic medication used in the treatment of Chagas disease.
Synonyms: Ro 71051; Ro 07-1051; Rochagan.
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Novel quinoline derivatives with broad-spectrum antiprotozoal activities
Carla B. Hartman ; Phelelisiwe S. Dube ; Lesetja J. Legoabe ; Natascha Van Pelt ; An Matheeussen ; Guy Caljon , et al.
Abstract: Several quinoline derivatives incorporating arylnitro and aminochalcone moieties were synthesized and evaluated in vitro against a broad panel of trypanosomatid protozoan parasites responsible for sleeping sickness (Trypanosoma brucei rhodesiense), nagana (Trypanosoma brucei brucei), Chagas disease (Trypanosoma cruzi), and leishmaniasis (Leishmania infantum). Several of the compounds demonstrated significant antiprotozoal activity. Specifically, compounds 2c, 2d, and 4i displayed submicromolar activity against T. b. rhodesiense with half-maximal effective concentration (EC50) values of 0.68, 0.8, and 0.19 µM, respectively, and with a high selectivity relative to human lung fibroblasts and mouse primary macrophages (∼100-fold). Compounds 2d and 4i also showed considerable activity against T. b. brucei with EC50 values of 1.4 and 0.4 µM, respectively.
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Keywords: anti‐infectives ; arylnitro ; chalcones ; protozoal ; quinoline
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CAS No. : | 22994-85-0 |
Formula : | C12H12N4O3 |
M.W : | 260.25 |
SMILES Code : | O=C(NCC1=CC=CC=C1)CN2C=CN=C2[N+]([O-])=O |
Synonyms : |
Ro 71051; Ro 07-1051; Rochagan.
|
MDL No. : | MFCD00243089 |
InChI Key : | CULUWZNBISUWAS-UHFFFAOYSA-N |
Pubchem ID : | 31593 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
In Vitro:
Concentration | Treated Time | Description | References |
Vero cells | 2000-50 μM | 48 h | To determine the cytotoxicity of Benznidazole | PMC8480776 |
RAW 264.7 macrophages | 15 µM | 30 min | To study the effect of Bzl on macrophage polarization, results showed Bzl inhibits M1 markers (NOx, IL-6, TNF-α, IL-17A) and increases M2 markers (Arginase I, MR, TGF-β, VEGF-A, PPAR-γ, PPAR-α). | PMC8675942 |
neonatal mouse primary cardiomyocytes | 15 µM | 30 min | To study the anti-inflammatory effect of Bzl on LPS-stimulated cardiomyocytes, results showed Bzl inhibits NF-κB pathway by increasing SOCS3 expression and reduces NOx release. | PMC8675942 |
cardiomyocytes | 15 µM | 30 min | To study the anti-inflammatory mechanisms of Benznidazole, it was found to inhibit the NF-κB pathway via the IL-10/STAT3/SOCS3 axis, reducing the expression of inflammatory mediators. | PMC6558013 |
Bloodstream trypomastigotes (BT) | 8.82 µM | 24 h | Assess the direct trypanocidal effect of Benznidazole on bloodstream trypomastigotes, demonstrating significant activity of Bz MT. | PMC9452897 |
Heart cells (HCs) | 5.4 µM | 72 h | Evaluate the trypanocidal effect of Benznidazole on intracellular T. cruzi, showing that Bz MT partially restored the cytoskeleton structure of infected cells after 72 h of treatment. | PMC9452897 |
Vero-C76 cells | 0.51 µM | 5 days | Evaluate the in vitro activity of Benznidazole against Trypanosoma cruzi, showing inhibitory effects on intracellular amastigotes. | PMC9294734 |
LN-18 glioma cells | 100 μM | 24 h | To evaluate the inhibitory effect of Benznidazole on clonogenic potential under hypoxic conditions. Results showed that Benznidazole significantly inhibited the clonogenic potential of LN-18 cells under severe hypoxia (approximately 0% O2). | PMC5199162 |
KNS42 glioma cells | 100 μM | 24 h | To evaluate the inhibitory effect of Benznidazole on clonogenic potential under hypoxic conditions. Results showed that Benznidazole significantly inhibited the clonogenic potential of KNS42 cells under severe hypoxia (approximately 0% O2). | PMC5199162 |
C33A cervical cancer cells | 100 μM | 24 h | To evaluate the inhibitory effect of Benznidazole on clonogenic potential under hypoxic conditions. Results showed that Benznidazole significantly inhibited the clonogenic potential of C33A cells under severe hypoxia (approximately 0% O2). | PMC5199162 |
HCT116 colon cancer cells | 100 μM | 24 h | To evaluate the inhibitory effect of Benznidazole on clonogenic potential under hypoxic conditions. Results showed that Benznidazole significantly inhibited the clonogenic potential of HCT116 cells under severe hypoxia (approximately 0% O2). | PMC5199162 |
MDA-MB-231 breast cancer cells | 500 μM | 24 h | To evaluate the inhibitory effect of Benznidazole on clonogenic potential under hypoxic conditions. Results showed that Benznidazole significantly inhibited the clonogenic potential of MDA-MB-231 cells under severe hypoxia (approximately 0% O2). | PMC5199162 |
SK-N-ER neuroblastoma cells | 500 μM | 24 h | To evaluate the inhibitory effect of Benznidazole on clonogenic potential under hypoxic conditions. Results showed that Benznidazole significantly inhibited the clonogenic potential of SK-N-ER cells under severe hypoxia (approximately 0% O2). | PMC5199162 |
T. cruzi Y strain bloodstream trypomastigotes | ≤8 μM | 24 h | Evaluate the activity of Benznidazole against T. cruzi Y strain bloodstream trypomastigotes, all quinolines except DB2171 and DB2192 were more effective than Bz | PMC5786769 |
L929 cells | 0.1 to 2.05 μM | 96 h | Evaluate the activity of Benznidazole against T. cruzi Tulahuen strain, all quinolines were more potent than Bz | PMC5786769 |
Trypanosoma cruzi bloodstream trypomastigotes | 50-0.1 μM | 24 h | To evaluate the trypanocidal activity of Benznidazole against T. cruzi bloodstream trypomastigotes | PMC8480776 |
Trypanosoma cruzi amastigotes | 50-0.1 μM | 72 h | To evaluate the trypanocidal activity of Benznidazole against T. cruzi amastigotes | PMC8480776 |
Trypanosoma cruzi epimastigotes | 50-0.5 μM | 48 h | To evaluate the trypanocidal activity of Benznidazole against T. cruzi epimastigotes | PMC8480776 |
In Vivo:
Administration | Dosage | Frequency | Description | References |
Mice | Acute Chagas disease model | 200 mg/Kg | To evaluate the inhibitory effect of Benznidazole on inflammatory responses in vivo, it was found to reduce parasite load and inflammatory reaction in heart tissue. | PMC6558013 | ||
BALB/cJ mice | Acute Trypanosoma cruzi infection model | Oral | 100 mg/kg | Once daily for 20 days | Evaluate the in vivo efficacy of Benznidazole alone or in combination with Miltefosine against Trypanosoma cruzi infection, showing significant reduction in parasitemia and mortality. | PMC9294734 |
Mice | Chronic Chagas cardiomyopathy model | Gavage | 25 mg/kg | Daily administration for 30 days | To evaluate the therapeutic effects of Benznidazole in a mouse model of chronic Chagas cardiomyopathy. Results showed that Bz treatment partially reversed ECG abnormalities and controlled parasite load. | PMC8351877 |
BALB/c mice | T. cruzi Arequipa strain infection model | Intraperitoneal injection | 20 mg/kg | Once daily for 5 consecutive days | To evaluate the therapeutic effect of Benznidazole in acute and chronic Chagas disease | PMC8480776 |
Mice | Acute infection model with T. cruzi Ninoa strain | Intragastric administration | 100 mg/kg body weight | Single dose, monitored for 8 hours | Evaluation of Gliquidone monotherapy on clearance of T. cruzi infection in mice, reducing infection by 40-60% | PMC11768481 |
Clinical Trial:
NCT Number | Conditions | Phases | Recruitment | Completion Date | Locations |
NCT02625974 | Chagas Disease | Phase 3 | Active, not recruiting | August 9, 2021 | Argentina ... More >> La Plata, Buenos Aires, Argentina, 1900 Buenos Aires, Ciudad Auton. De Buenos Aires, Argentina, 1281 Buenos Aires, Ciudad Auton. De Buenos Aires, Argentina, C1270AAN Buenos Aires, Ciudad Auton. De Buenos Aires, Argentina, C1425AGP Buenos Aires, Ciudad Auton. De Buenos Aires, Argentina, C1425EFD San Salvador de Jujuy, Jujuy, Argentina, 4600 Posadas, Misiones, Argentina Rosario, Santa Fe, Argentina, 2000 Corrientes, Argentina, W3400CBI Formosa, Argentina, P3600HZL La Rioja, Argentina Mendoza, Argentina, 5500 Mendoza, Argentina, 5535 Salta, Argentina, 4400 Salta, Argentina, A4400ESE San Juan, Argentina, 5400 Santiago del Estero, Argentina, 4202 Tucuman, Argentina, 4000 Bolivia Cochabamba, Bolivia Punata, Bolivia Tarija, Bolivia Colombia Barranquilla, Atlántico, Colombia Yopal, Casanare, Colombia, 0 Santa Marta, Magdalena, Colombia, 0 Floridablanca, Santander, Colombia Less << |
NCT01377480 | Chagas Disease | Phase 2 | Completed | - | - |
NCT01377480 | - | Completed | - | - | |
NCT01755377 | Chagas Disease | COMPLETED | 2025-06-16 | International Health Departmen... More >>t, Hospital Clinic, Barcelona, Barcelona, Catalu?a, 08036, Spain Less << | |
NCT02369978 | Chagas Disease | Phase 2 Phase 3 | Recruiting | February 2019 | Colombia ... More >> Fundación Oftalmológica de Santander - Clínica Ardila Lulle (FOSCAL) Recruiting Bucaramanga, Santander, Colombia Contact: Gustavo A Parra, MD guparra@unab.edu.co Contact: Skarlet M Vásquez, RN, MSc svasquez196@unab.edu.co Less << |
NCT01489228 | Chronic Chagas Disease, Indete... More >>rminate Less << | Phase 2 | Unknown | December 2013 | Bolivia ... More >> Plataforma de Atención Integral a los Pacientes con Enfermidad de Chagas Recruiting Cochabamba, Bolivia Contact: Faustino Torrico, PhD Contact: Cristina Alonso, MD Principal Investigator: Faustino Torrico, PhD Plataforma de Atención Integral a los Pacientes con Enfermidad de Chagas Recruiting Tarija, Bolivia Contact: Lourdes Ortiz, MSc Sub-Investigator: Lourdes Ortiz, MSc Less << |
NCT01678599 | Chagas Disease | PHASE4 | COMPLETED | 2025-04-13 | Medicin Sans Frontièrs (MSF), ... More >>Aiquile, Bolivia Less << |
NCT01162967 | Chagas Disease | Phase 2 | Completed | - | Spain ... More >> International Health Unit Metropolitana Nord Santa Coloma, Barcelona, Spain Infectious Disease Department Vall d'Hebron Hospital Barcelona, Spain International Health Unit Drassanes Barcelona, Spain Less << |
NCT03378661 | Chagas Disease | Phase 2 | Active, not recruiting | July 27, 2018 | Bolivia ... More >> Plataforma de Atención Integral de Pacientes con Enfermedad de Chagas. Sucre, Chuquisaca, Bolivia Plataforma de Atención Integral de Pacientes con Enfermedad de Chagas. Cochabamba, Bolivia Plataforma de Atención Integral de Pacientes con Enfermedad de Chagas. Tarija, Bolivia Less << |
NCT01549236 | Chagas' Disease | Phase 4 | Completed | - | Argentina ... More >> Hospital General de Niños Ricardo Gutierrez Buenos Aires, Argentina, C1425 Hospital de Niños "Doctor Héctor Quintana" Jujuy, Argentina, CP4600 Hospital Público Materno Infantil Salta, Argentina, CP3400 Less << |
NCT00123916 | Chagas Disease ... More >> Trypanosomiasis Heart Disease Less << | Phase 3 | Unknown | July 2013 | - |
NCT01755403 | Chagas Disease | PHASE4 | COMPLETED | 2025-11-13 | International Health Departmen... More >>t, Hospital Clinic, Barcelona, Barcelona, Catalu?a, 08036, Spain Less << |
NCT03672487 | Chagas Disease | Phase 3 | Not yet recruiting | May 31, 2023 | United States, California ... More >> University of California at San Diego Not yet recruiting San Diego, California, United States, 92093 Contact: Edmund Capparelli, PharmD 858-246-0009 ecapparelli@ucsd.edu Principal Investigator: Edmund Capparelli, PharmD Sub-Investigator: Jeremiah Momper, PhD United States, Louisiana Tulane School of Public Health and Tropical Medicine Not yet recruiting New Orleans, Louisiana, United States, 70112 Contact: Pierre Buekens, MD, PhD 504-988-8803 pbuekens@tulane.edu Principal Investigator: Pierre Buekens, MD, PhD Sub-Investigator: Eric Dumonteil, PhD Sub-Investigator: Claudia Herrera, PhD Sub-Investigator: Jeffrey Shaffer, PhD Argentina Institute for Clinical Effectiveness and Health Policy Not yet recruiting Buenos Aires, Argentina Contact: Fernando Althabe, MD, MSc falthabe@gmail.com Principal Investigator: Fernando Althabe, MD, MSc Sub-Investigator: Maria Luisa Cafferata, MD Sub-Investigator: Eduardo Bergel, MSc, PhD Sub-Investigator: Mabel Berrueta, MD Sub-Investigator: Jose Belizan, MD, PhD Sub-Investigator: Sergio Sosa-Estani, MD, PhD Sub-Investigator: Alejandro Schijman, DSc Less << |
NCT01547533 | - | Completed | - | Argentina ... More >> Parasitology and Chagas Service, Buenos Aires Children´s Hospital Ricardo Gutierrez Buenos Aires, Argentina, 1425 Less << | |
NCT03739541 | Healthy Male Subjects | Phase 1 | Completed | - | United Kingdom ... More >> Covance Leeds, United Kingdom, LS2 9LH Less << |
NCT03191162 | Chagas Disease|Trypanosoma Cru... More >>zi Infection Less << | PHASE2 | COMPLETED | 2021-03-16 | Instituto Nacional de Parasito... More >>logía Dr. Mario Fatala Chaben (ANLIS), Buenos Aires, Argentina|Instituto de Cardiología de Corrientes Juana Francisca Cabral, Corrientes, Argentina|Centro de Pesquisas René Rachou - Funda??o Oswaldo Cruz. (FIOCRUZ), Belo Horizonte, Brazil|Hospital Universitário Clemente de Faria, Montes Claros, Brazil|Fundación Cardioinfantil - Instituto de Cardiología, Bogotá, Colombia|Centro Atencion y Diagnóstico de Enfermedades Infecciosas, Bucaramanga, Colombia|Infectious Disease Department Vall d'Hebron Hospital, Barcelona, Spain Less << |
NCT00699387 | Chagas Disease | COMPLETED | 2025-05-11 | Parasitology Division, Childre... More >>n's Hospital "R Gutierrez" of Buenos Aires, Buenos Aires, 1425, Argentina Less << | |
NCT02386358 | Chagas Disease | Phase 3 | Completed | - | Argentina ... More >> Instituto Nacional de Parasitología Dr Mario Fatala Chaben Ciudad Autónoma de Buenos Aires, Buenos Aires, Argentina, 1063 Less << |
NCT04024163 | Chagas Disease | PHASE3 | ACTIVE_NOT_RECRUITING | 2028-03-30 | Hospital de Ninos "Dr. Ricardo... More >> Gutierrez", Ciudad Autónoma de Buenos Aires, Argentina|Hospital "Luis Carlos Lagomaggiore", Mendoza, Argentina|Hospital Pediatrico "Dr. Humberto Notti", Mendoza, Argentina|Hospital Público Descentralizado Dr. Guillermo Rawson, San Juan, Argentina|Centro de Enfermedad de Chagas y Patologías Regionales, Santiago Del Estero, Argentina|Antigua Hospital Viedma, Cochabamba, Bolivia|CEADES - Plataforma de Chagas Sucre, Sucre, Bolivia|Fundación Salud para el Trópico, Santa Marta, Colombia|Centro de Atención e Investigación Médica (CAIMED), Yopal, Colombia Less << |
Bio Calculators | ||||
Preparing Stock Solutions | ![]() |
1mg | 5mg | 10mg |
1 mM 5 mM 10 mM |
3.84mL 0.77mL 0.38mL |
19.21mL 3.84mL 1.92mL |
38.42mL 7.68mL 3.84mL |
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Dissolving Methods |
in order to ensure the reliability of the experimental results, the clarified stock solution can be properly preserved according to the storage conditions; The working fluid for in vivo experiment is recommended to be prepared now and used on the same day; The percentage shown in front of the following solvent refers to the volume ratio of the solvent in the final solution; If precipitation or precipitation occurs in the preparation process, it can be assisted by heating and/or ultrasound. Please choose the appropriate dissolution scheme according to your animal administration guide.For the following dissolution schemes, clear stock solution should be prepared according to in vitro experiments, and then cosolvent should be added in turn:
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