title: Potential amoebicidal activity of hydrazone derivatives: synthesis, characterization, electrochemical behavior, theoretical study and evaluation of the biological activity.
abstract: Four new hydrazones were synthesized by the condensation of the selected hydrazine and the appropriate nitrobenzaldehyde. A complete characterization was done employing 1H- and 13C-NMR, electrochemical techniques and theoretical studies. After the characterization and electrochemical analysis of each compound, amoebicidal activity was tested in vitro against the HM1:IMSS strain of Entamoeba histolytica. The results showed the influence of the nitrobenzene group and the hydrazone linkage on the amoebicidal activity. meta-Nitro substituted compound 2 presents a promising amoebicidal activity with an IC50 = 0.84 μM, which represents a 7-fold increase in cell growth inhibition potency with respect to metronidazole (IC50 = 6.3 μM). Compounds 1, 3, and 4 show decreased amoebicidal activity, with IC50 values of 7, 75 and 23 µM, respectively, as a function of the nitro group position on the aromatic ring. The observed differences in the biological activity could be explained not only by the redox potential of the molecules, but also by their capacity to participate in the formation of intra- and intermolecular hydrogen bonds. Redox potentials as well as the amoebicidal activity can be described with parameters obtained from the DFT analysis.
authors.affiliation: Departamento de Inmunología, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Avenida Universidad 3000, 04510 Mexico City, Mexico. yanistoledano@gmail.com.
authors.forename: Yanis
authors.initials: Y
authors.lastname: Toledano-Magaña
authors.affiliation: Laboratorio de Química Inorgánica Medicinal, Departamento de Química Inorgánica y Nuclear, Facultad de Química, Universidad Nacional Autónoma de México, Avenida Universidad 3000, 04510 Mexico City, Mexico. johnycarbonilo@gmail.com.
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: García-Ramos
authors.affiliation: Departamento de Química Orgánica, Facultad de Ciencias Químicas, Benemérita Universidad Autónoma de Puebla, 72570 Puebla, Mexico. marisol-navarro@hotmail.com.
authors.forename: Marisol
authors.initials: M
authors.lastname: Navarro-Olivarria
authors.affiliation: Facultad de Química, Universidad Nacional Autónoma de México, Avenida Universidad 3000, 04510 Mexico City, Mexico. mfa@unam.mx.
authors.forename: Marcos
authors.initials: M
authors.lastname: Flores-Alamo
authors.affiliation: Departamento de Electroquímica, Centro de Investigación y Desarrollo Tecnológico en Electroquímica, S.C., Parque Tecnológico Querétaro, Sanfandila, Pedro de Escobedo, C.P. 76703 Querétaro, México. aryamm@hotmail.com.
authors.forename: Mayra
authors.initials: M
authors.lastname: Manzanera-Estrada
authors.affiliation: Departamento de Electroquímica, Centro de Investigación y Desarrollo Tecnológico en Electroquímica, S.C., Parque Tecnológico Querétaro, Sanfandila, Pedro de Escobedo, C.P. 76703 Querétaro, México. lortiz@cideteq.mx.
authors.forename: Luis
authors.initials: L
authors.lastname: Ortiz-Frade
authors.affiliation: Department of Medicinal Chemistry, College of Pharmacy, University of Utah, 2000 East 30 South Skaggs 201, Salt Lake City, UT 84112, USA. rodrigogalindo@gmail.com.
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Galindo-Murillo
authors.affiliation: Laboratorio de Química Inorgánica Medicinal, Departamento de Química Inorgánica y Nuclear, Facultad de Química, Universidad Nacional Autónoma de México, Avenida Universidad 3000, 04510 Mexico City, Mexico. lenar701@gmail.com.
authors.forename: Lena
authors.initials: L
authors.lastname: Ruiz-Azuara
authors.affiliation: Departamento de Química Orgánica, Facultad de Ciencias Químicas, Benemérita Universidad Autónoma de Puebla, 72570 Puebla, Mexico. ruthmelendrez@gmail.com.
authors.forename: Ruth Ma
authors.initials: RM
authors.lastname: Meléndrez-Luevano
authors.affiliation: Departamento de Química Orgánica, Facultad de Ciencias Químicas, Benemérita Universidad Autónoma de Puebla, 72570 Puebla, Mexico. bmcabreravivas@yahoo.com.
authors.forename: Blanca M
authors.initials: BM
authors.lastname: Cabrera-Vivas
mesh_terms: D000563:Amebicides / Q000138:chemical synthesis / Q000494:pharmacology*; D001547:Benzaldehydes / Q000737:chemistry*; D055664:Electrochemical Techniques; D004748:Entamoeba histolytica / Q000187:drug effects*; D006834:Hydrazines / Q000737:chemistry*; D006835:Hydrazones / Q000138:chemical synthesis / Q000494:pharmacology*; D006860:Hydrogen Bonding; D020128:Inhibitory Concentration 50; D008795:Metronidazole / Q000494:pharmacology; D009578:Nitrobenzenes / Q000737:chemistry*; D010084:Oxidation-Reduction; D011789:Quantum Theory; D013329:Structure-Activity Relationship
chemical_list: D000563:Amebicides; D001547:Benzaldehydes; D006834:Hydrazines; D006835:Hydrazones; D009578:Nitrobenzenes; D008795:Metronidazole; C029424:hydrazine
keywords: DFT; Entamoeba histolytica; ROS production; amoebicidal activity; electrochemistry; hydrazone; hydrogen bonds