Recent Advances in the Development of Triose Phosphate Isomerase Inhibitors as Antiprotozoal Agents

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AudienciaPúblico en generales_ES
CoberturaMéxicoes_ES
Fecha de ingreso2026-09-15T00:30:13Z
Fecha de publicación2022-01-01
ResumenBackground: Parasitic diseases caused by protozoa, such as Chagas disease, leishmaniasis, malaria, African trypanosomiasis, amoebiasis, trichomoniasis, and giardiasis, are considered serious public health problems in developing countries. Drug resistance among parasites justifies the search for new therapeutic drugs, and the identification of new targets becomes a valuable approach. In this scenario, the glycolysis pathway, which converts glucose into pyruvate, plays an important role in the protozoa energy supply, and it is therefore considered a promising target. In this pathway, triose phosphate isomerase (TIM) plays an essential role in efficient energy production. Furthermore, protozoa TIM shows structural differences with human enzyme counterparts, suggesting the possibility of obtaining selective inhibitors. Therefore, TIM is considered a valid approach to develop new antiprotozoal agents, inhibiting the glycolysis in the parasite. Objective: In this review, we discuss the drug design strategies, structure-activity relationship, and binding modes of outstanding TIM inhibitors against Trypanosoma cruzi, Trypanosoma brucei, Plasmodium falciparum, Giardia lamblia, Leishmania mexicana, Trichomonas vaginalis, and Entamoeba histolytica. Results: TIM inhibitors have mainly shown aromatic systems and symmetrical structure, where the size and type of heteroatom are important for enzyme inhibition. This inhibition is mainly based on the interaction with i) the interfacial region of TIM inducing changes on the quaternary and tertiary structure or ii) with the TIM catalytic region, the main pathways that disable the catalytic activity of the enzyme. Conclusion: Benzothiazole, benzoxazole, benzimidazole, and sulfhydryl derivatives stand out as TIM inhibitors. In silico and in vitro studies have demonstrated that the inhibitors bind mainly at the TIM dimer interface. In this review, the development of new TIM inhibitors as antiprotozoal drugs is demonstrated as an important pharmaceutical strategy that may lead to new therapies for these ancient parasitic diseases.es_ES
Doihttps://doi.org/10.2174/0929867328666210913090928es_ES
URIhttps://riuat.uat.edu.mx/handle/123456789/2165
Idiomaeses_ES
EditorialBentham Science Publishers Ltd.es_ES
RelaciónCurrent Medicinal Chemistryes_ES
URL relacionadohttps://doi.org/10.2174/0929867328666210913090928es_ES
DerechosAcceso abierto (Metadatos de producción científica)es_ES
Licenciahttp://purl.org/coar/access_right/c_abf2es_ES
FuenteCurrent Medicinal Chemistry
TítuloRecent Advances in the Development of Triose Phosphate Isomerase Inhibitors as Antiprotozoal Agentses_ES
TipoArtículoes_ES
ArbitradoHa sido Arbitradoes_ES
AutorVázquez-Jiménez, Lenci K.
AutorMoreno-Herrera, Antonio
AutorJuárez-Saldivar, Alfredo
AutorGonzález-González, Alonzo
AutorOrtiz-Pérez, Eyra
AutorPaz-González, Alma D.
AutorPalos, Isidro
AutorRamírez-Moreno, Esther
AutorRivera, Gildardo
AutorVázquez-Jiménez, Lenci K.es_ES
AutorMoreno-Herrera, Antonioes_ES
AutorJuárez-Saldivar, Alfredoes_ES
AutorGonzález-González, Alonzoes_ES
AutorOrtiz-Pérez, Eyraes_ES
AutorPaz-González, Alma D.es_ES
AutorPalos, Isidroes_ES
AutorRamírez-Moreno, Estheres_ES
AutorRivera, Gildardoes_ES
InstituciónUniversidad Autónoma de Tamaulipas
InstituciónUniversidad Autónoma de Tamaulipases_ES
Número14es_ES
Rango de páginas2504-2529es_ES
URL relacionadahttps://doi.org/10.2174/0929867328666210913090928
Tipo de artículoIndexado
Tipo de artículoIndexadoes_ES
Volumen29es_ES

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