title: Synthesis, antimycobacterial and cytotoxic activity of α,β-unsaturated amides and 2,4-disubstituted oxazoline derivatives.
abstract: The synthesis of six α,β,-unsaturated amides and six 2,4-disubstituted oxazolines derivatives and their evaluation against two Mycobacterium tuberculosis strains (sensitive H37Rv and a resistant clinical isolate) is reported. 2,4-Disubstituted oxazolines (S)-3b,d,e were the most active in the sensitive strain with a MIC of 14.2, 13.6 and 10.8μM, respectively, and the compounds (S)-3d,f were the most active against resistant strain with a MIC of 6.8 and 7.4μM. The ex-vivo evaluation of hepatotoxicity on precision-cut rat liver slices was also tested for the α,β-unsaturated amides (S)-2b and (S)-2d,f and for the oxazolines (S)-3b and (S)-3d,f at different concentrations (5, 15 and 30μg/mL). The results indicate that these compounds possess promising antimycobacterial activity and at the same time are not hepatotoxic. These findings open the possibility for development of new drugs against tuberculosis.
authors.affiliation: Universidad Autónoma de Nuevo León, Facultad de Ciencias Químicas, Pedro de Alba s/n, Ciudad Universitaria, 66400 San Nicolás de los Garza, Nuevo León, Mexico.
authors.forename: Francisco G
authors.initials: FG
authors.lastname: Avalos-Alanís
authors.affiliation: Universidad Autónoma de Nuevo León, Facultad de Ciencias Químicas, Pedro de Alba s/n, Ciudad Universitaria, 66400 San Nicolás de los Garza, Nuevo León, Mexico. Electronic address: eugenio.hernandezfr@uanl.edu.mx.
authors.forename: Eugenio
authors.initials: E
authors.lastname: Hernández-Fernández
authors.affiliation: Centro de Investigación Biomédica del Noreste, Instituto Mexicano del Seguro Social, Monterrey, Nuevo León, Mexico. Electronic address: pilarcarranza@cibinmty.net.
authors.forename: Pilar
authors.initials: P
authors.lastname: Carranza-Rosales
authors.affiliation: Universidad Autónoma de Nuevo León, Facultad de Ciencias Químicas, Pedro de Alba s/n, Ciudad Universitaria, 66400 San Nicolás de los Garza, Nuevo León, Mexico.
authors.forename: Susana
authors.initials: S
authors.lastname: López-Cortina
authors.affiliation: Universidad Autónoma de Nuevo León, Facultad de Ciencias Químicas, Pedro de Alba s/n, Ciudad Universitaria, 66400 San Nicolás de los Garza, Nuevo León, Mexico.
authors.forename: Jorge
authors.initials: J
authors.lastname: Hernández-Fernández
authors.affiliation: Centro de Investigaciones Químicas-IICBA, Universidad Autónoma del Estado de Morelos, Av. Universidad 1001, 62209 Cuernavaca, Morelos, Mexico.
authors.forename: Mario
authors.initials: M
authors.lastname: Ordóñez
authors.affiliation: Unidad Médica de Alta Especialidad 34, Instituto Mexicano del Seguro Social, 64730 Monterrey, Nuevo León, Mexico.
authors.forename: Nancy E
authors.initials: NE
authors.lastname: Guzmán-Delgado
authors.affiliation: Laboratorio Estatal de Salud Pública, Secretaría de Salud, 67180 Guadalupe, Nuevo León, Mexico.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Morales-Vargas
authors.affiliation: Laboratorio Estatal de Salud Pública, Secretaría de Salud, 67180 Guadalupe, Nuevo León, Mexico.
authors.forename: Víctor M
authors.initials: VM
authors.lastname: Velázquez-Moreno
authors.affiliation: Centro de Investigación Biomédica del Noreste, Instituto Mexicano del Seguro Social, Monterrey, Nuevo León, Mexico.
authors.forename: María G
authors.initials: MG
authors.lastname: Santiago-Mauricio
mesh_terms: D000577:Amides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D000818:Animals; D000995:Antitubercular Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008826:Microbial Sensitivity Tests; D008853:Microscopy; D009169:Mycobacterium tuberculosis / Q000187:drug effects; D010080:Oxazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D051381:Rats; D013329:Structure-Activity Relationship
chemical_list: D000577:Amides; D000995:Antitubercular Agents; D010080:Oxazoles
keywords: Antimycobacterial activity; Hepatotoxic activity; Organic synthesis; Unsaturated amides; α,β-2,4-Disubstituted oxazolines