Desarrollo de fármacos para tratar la teniasis y cisticercosis

Ponciano  García Gutiérrez

Ponciano García Gutiérrez Departamento de Química, Universidad Autónoma Metropolitana-Iztapalapa

Keywords: Taenia solium, drug design, glutathione transferases, enzyme inhibitor

Abstract

Taenia solium causes taeniasis in humans and cysticercosis in pigs and humans. Neurocysticercosis affects more than 20 million people worldwide and is the cause of more than 50 thousand deaths each year. Glutathione transferase enzymes in helminths such as Taenia solium represent the main cellular detoxification mechanism available, which is why they are considered targets for drug design. To date, three glutathione transferase enzymes have been identified in Taenia solium. Resistance to broad-spectrum anthelmintics has been reported, establishing the need to develop new treatments. Our work focuses on developing a specific high-affinity inhibitor for each of these enzymes, as part of the development of a drug to treat human taeniasis and human and porcine cysticercosis.

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References

Armstrong, R.N. Structure, catalytic mechanism, and evolution of the glutathione transferases. Chem. Res. Toxicol. 10(1), 2-18, 1997.

Bhattarai, R., Carabin, H., Proaño, J. V., Flores-Rivera, J., Corona, T., Flisser, A., León-Maldonado, L., & Budke, C. M. The monetary burden of cysticercosis in Mexico. PLoS Negl. Trop. Dis.13(7), e0007501, 2029.

Cárdenas, G., Carrillo-Mezo, R., Jung, H., Sciutto, E., Hernandez, J. L., Fleury, A. Subarachnoidal Neurocysticercosis non-responsive to cysticidal drugs: a case series. BMC Neurol. 10(16), 2010.

Frova, C. Glutathione transferases in the genomics era: new insights and perspectives. Biomol. Eng. 23(4), 149-169, 2006.

García-Gutiérrez, P., Zubillaga, R.A., Téllez- Plancarte, A., Flores-López, R., Camarillo- Cadena, M., Landa, A. Discovery of a new non-substrate inhibitor of the 26.5 kDa glutathione transferase from Taenia solium by virtual screening. J. Mol. Graph. Model. 100, 2020.

Miranda-Blancas R, Rodríguez-Lima O, García-Gutiérrez P, Flores-López R, Jiménez L, Zubillaga RA, Rudiño-Piñera E, Landa A. Biochemical characterization and gene structure analysis of the 24-kDa glutathione transferase sigma from Taenia solium. FEBS Open Bio. 14(5), 726- 739, 2024.

Overbosch, D., van de Nes, J.C., Groll, E., Diekmann, H.W., Polderman, A.M., Mattie, H. (1987) Penetration of praziquantel into cerebrospinal fluid and cysticerci in human cysticercosis. Eur. J. Clin. Pharmacol. 33(3), 287-292, 1987.

Roldan, A., Torres-Rivera, A., Landa, A. Structural and biochemical studies of a recombinant 25.5 kDa glutathione transferase of Taenia solium metacestode (rTs25GST1-1). Parasitol Res. 112(11), 3865– 3872, 2013.

Torres-Rivera, A., Landa, A. Cooperative kinetics of the recombinant glutathione transferase of Taenia solium and characterization of the enzyme. Arch. Biochem. Biophys. 477(2), 372–378, 2008.

Townsend, D.M., Tew, K.D., The role of glutathione-S-transferase in anti-cancer drug resistance, Oncogene. 22(47), 7369- 7375, 2003.