Effect of Trichomonacide 6-Nitro-1H-benzimidazole Derivative Compounds on Expression Level of Metabolic Genes in Trichomonas vaginalis

Author:

Gutiérrez-Cardona Jocelyn Yamin1,Calderón-Jaimes Ernesto1,Ortega-Cuellar Daniel2ORCID,Sánchez-Carrillo Adrián1,Castillo-Rodríguez Rosa Angélica3ORCID,Canseco-Ávila Luis Miguel4ORCID,Rocha-Ramírez Luz María5ORCID,Martínez-Rosas Víctor6ORCID,Gómez-Manzo Saúl6ORCID,Hernández-Ochoa Beatriz1

Affiliation:

1. Laboratorio de Inmunoquímica, Hospital Infantil de México Federico Gómez, Secretaría de Salud, Mexico City 06720, Mexico

2. Laboratorio de Nutrición Experimental, Instituto Nacional de Pediatría, Secretaría de Salud, Mexico City 04530, Mexico

3. Centro de Investigacion en Ciencia Aplicada y Tecnología Avanzada (CICATA) Unidad Morelos, Instituto Politécnico Nacional, Boulevard de la Tecnología, 1036 Z-1, P 2/2, Atlacholoaya 62790, Mexico

4. Facultad de Ciencias Químicas, Campus IV, Universidad Autónoma de Chiapas, Tapachula City 30580, Mexico

5. Unidad de Investigación en Enfermedades Infecciosas, Hospital Infantil de México Federico Gómez, Dr. Márquez No. 162, Colonia Doctores, Mexico City 06720, Mexico

6. Laboratorio de Bioquímica Genética, Instituto Nacional de Pediatría, Secretaría de Salud, Mexico City 04530, Mexico

Abstract

The parasite Trichomonas vaginalis is the etiologic agent of trichomoniasis, the most common non-viral sexually transmitted disease worldwide. This infection often remains asymptomatic and is related to several health complications. The traditional treatment for trichomoniasis is the use of drugs of the 5-nitroimidazole family, such as metronidazole; however, scientific reports indicate an increasing number of drug-resistant strains. Benzimidazole derivatives could offer an alternative in the search for new anti-trichomonas drugs. In this sense, two attractive candidates are the compounds O2N-BZM7 and O2N-BZM9 (1H-benzimidazole derivatives), since, through in vitro tests, they have shown a higher trichomonacide activity. In this study, we determined the effect on the expression level of metabolic genes in T. vaginalis. The results show that genes involved in redox balance (NADHOX, G6PD::6PGL) are overexpressed, as well as the gene that participates in the first reaction of glycolysis (CK); on the other hand, structural genes such as ACT and TUB are decreased in expression in trophozoites treated with the compound O2N-BZM9, which would probably affect its morphology, motility and virulence. These results align with the trichomonacidal activity of the compounds, with benzimidazole O2N-BZM9 being the most potent, with an IC50 value of 4.8 μM. These results are promising for potential future therapeutic applications.

Funder

Hospital Infantil de Mexico Federico Gómez, Mexico City, Mexico

E022 Program, National Institute of Pediatrics, Mexico City, Mexico (Recursos Fiscales para la Investigación).

Publisher

MDPI AG

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