Potential Amoebicidal Activity of Hydrazone Derivatives: Synthesis, Characterization, Electrochemical Behavior, Theoretical Study and Evaluation of the Biological Activity

Molecules

Yanis Toledano-Maga༚¹  Juan Carlos Garc໚-Ramos⁶  Marisol Navarro-Olivarria²  Marcos Flores-Alamo⁵  Mayra Manzanera-Estrada⁴  Luis Ortiz-Frade⁴  Rodrigo Galindo-Murillo³  Lena Ruiz-Azuara⁶  Ruth Ma. Meléndrez-Luevano²  Blanca M. Cabrera-Vivas² 

[1]Departamento de Inmunología, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Avenida Universidad 3000, 04510 Mexico City, Mexico

[2] E-Mail:

[3]Departamento de Química Orgánica, Facultad de Ciencias Químicas, Benemérita Universidad Autónoma de Puebla, 72570 Puebla, Mexico

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[5]Department of Medicinal Chemistry, College of Pharmacy, University of Utah, 2000 East 30 South Skaggs 201, Salt Lake City, UT 84112, USA

[6] E-Mail:

[7]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

[8] E-Mails:

[9]Facultad de Química, Universidad Nacional Autónoma de México, Avenida Universidad 3000, 04510 Mexico City, Mexico

[10] E-Mail:

[11]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

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关键词: hydrazone;    amoebicidal activity;    ROS production;    electrochemistry;    DFT;    hydrogen bonds;    Entamoeba histolytica;   

DOI  :  10.3390/molecules20069929

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2015 by the authors; licensee MDPI, Basel, Switzerland.