title: A new type of quinoxalinone derivatives affects viability, invasion, and intracellular growth of Toxoplasma gondii tachyzoites in vitro.
abstract: Quinoxalinone derivatives, identified as VAM2 compounds (7-nitroquinoxalin-2-ones), were evaluated against Toxoplasma gondii tachyzoites of the RH strain. The VAM2 compounds were previously synthesized based on the design obtained from an in silico prediction with the software TOMOCOMD-CARDD. From the ten VAM2 drugs tested, several showed a deleterious effect on tachyzoites. However, VAM2-2 showed the highest toxoplasmicidal activity generating a remarkable decrease in tachyzoite viability (in about 91 %) and a minimal alteration in the host cell. An evident inhibition of host cell invasion by tachyzoites previously treated with VAM2-2 was observed in a dose-dependent manner. In addition, remarkable alterations were observed in the pellicle parasite, such as swelling, roughness, and blebbing. Toxoplasma motility was inhibited, and subpellicular cytoskeleton integrity was altered, inducing a release of its components to the soluble fraction. VAM2-2 showed a clear and specific deleterious effect on tachyzoites viability, structural integrity, and invasive capabilities with limited effects in host cells morphology and viability. VAM2-2 minimum inhibitory concentration (MIC50) was determined as 3.3 μM ± 1.8. Effects of quinoxalinone derivatives on T. gondii provide the basis for a future therapeutical alternative in the treatment of toxoplasmosis.
authors.affiliation: Departamento de Microbiología y Parasitología, Facultad de Medicina, Universidad Nacional Autónoma de México, Coyoacán 04510, DF, México.|Departamento de Bioquímica, Centro de Investigación y de Estudios Avanzados del IPN (CINVESTAV), Avenida IPN No 2508 Delegación Gustavo A Madero, 07360, DF, México.
authors.forename: Norma
authors.initials: N
authors.lastname: Rivera Fernández
authors.affiliation: Departamento de Bioquímica, Centro de Investigación y de Estudios Avanzados del IPN (CINVESTAV), Avenida IPN No 2508 Delegación Gustavo A Madero, 07360, DF, México.
authors.forename: Mónica
authors.initials: M
authors.lastname: Mondragón Castelán
authors.affiliation: Unidad de Microscopía Electrónica (LANSE), CINVESTAV, DF, Mexico.
authors.forename: Sirenia
authors.initials: S
authors.lastname: González Pozos
authors.affiliation: Departamento de Bioquímica, Centro de Investigación y de Estudios Avanzados del IPN (CINVESTAV), Avenida IPN No 2508 Delegación Gustavo A Madero, 07360, DF, México.
authors.forename: Carlos J
authors.initials: CJ
authors.lastname: Ramírez Flores
authors.affiliation: Departamento de Genética y Biología Molecular, CINVESTAV, DF, Mexico.
authors.forename: Ricardo
authors.initials: R
authors.lastname: Mondragón González
authors.affiliation: Departamento de Bioquímica, Centro de Investigación y de Estudios Avanzados del IPN (CINVESTAV), Avenida IPN No 2508 Delegación Gustavo A Madero, 07360, DF, México.
authors.forename: Carmen T
authors.initials: CT
authors.lastname: Gómez de León
authors.affiliation: Departamento de Bioquímica, Centro de Investigación y de Estudios Avanzados del IPN (CINVESTAV), Avenida IPN No 2508 Delegación Gustavo A Madero, 07360, DF, México.
authors.forename: Kitzia N
authors.initials: KN
authors.lastname: Castro Elizalde
authors.affiliation: Edificio de Especialidades Médicas, Hospital de los Valles, Colegio de Ciencias de la Salud, Universidad de San Francisco de Quito, Av. Interoceánica Km 12 1/2 Cumbayá, Quito, Ecuador.
authors.forename: Yovani
authors.initials: Y
authors.lastname: Marrero Ponce
authors.affiliation: Instituto de Química Médica, CSIC, c/ Juan de la Cierva 3, 28006, Madrid, España.
authors.forename: Vicente J
authors.initials: VJ
authors.lastname: Arán
authors.affiliation: Instituto de Química Médica, CSIC, c/ Juan de la Cierva 3, 28006, Madrid, España.|Centro de Investigaciones en Hidratos de Carbono (CIHIDECAR-CONICET), Departamento de Química Orgánica, FCEN y LabMOr - INTECIN, FI, UBA, Paseo Colón 850, 5to. Piso, CP C1063ACV, Buenos Aires, Argentina.
authors.forename: Miriam A
authors.initials: MA
authors.lastname: Martins Alho
authors.affiliation: Departamento de Bioquímica, Centro de Investigación y de Estudios Avanzados del IPN (CINVESTAV), Avenida IPN No 2508 Delegación Gustavo A Madero, 07360, DF, México. rmflores@cinvestav.mx.
authors.forename: Ricardo
authors.initials: R
authors.lastname: Mondragón Flores
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D003599:Cytoskeleton; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D011810:Quinoxalines / Q000494:pharmacology*; D014122:Toxoplasma / Q000187:drug effects* / Q000502:physiology / Q000648:ultrastructure; D014123:Toxoplasmosis / Q000469:parasitology
chemical_list: D011810:Quinoxalines
keywords: Apicomplexan; In silico drug design; Pellicle; Quinoxalinone derivatives; TOMOCOMD-CARDD; Toxoplasma gondii