Evaluación de compuestos nitro-tiazólicos en cepas de Giardia lamblia sensibles y resistentes a Nitazoxanida; expresión diferencial de genes, alteraciones estructurales y muerte celular.

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Title:	Evaluación de compuestos nitro-tiazólicos en cepas de Giardia lamblia sensibles y resistentes a Nitazoxanida; expresión diferencial de genes, alteraciones estructurales y muerte celular.
Alternate Title:	Evaluation of nitro-thiazole compounds in Giardia lamblia strains susceptible and resistant to nitazoxanide: differential gene expression, structural alterations, and cell death.
Authors:	Hernández-Ochoa, Beatriz¹, Navarrete-Vázquez, Gabriel², Morales-Luna, Laura³, Vázquez-Bautista, Montserrat^3,4, Hernández-Urzúa, Elizabeth⁵, González-Valdez, Abigail⁶, Enríquez-Flores, Sergio⁷, De la Mora De la Mora, Ignacio⁷, Arreguin-Espinosa, Roberto⁸, Vidal-Limon, Abraham⁹, Gómez-Manzo, Saúl³ saulmanzo@ciencias.unam.mx
Source:	Acta Pediatrica de Mexico. 2026 Supplement, Vol. 47, pS65-S66. 2p.
Subjects:	GIARDIA lamblia, METABOLISM, THIAZOLIUM compounds, MOLECULAR docking, GENE expression, ANTIPARASITIC agents, DRUG resistance, CELL death
Abstract (English):	BACKGROUND: Giardiasis is an intestinal disease with a growing prevalence of antiparasitic-resistant strains of Giardia lamblia, underscoring the need to identify new therapeutic candidates. OBJECTIVE: Evaluate the effect of seven nitro-thiazole compounds on viability and metabolism in G. lamblia. MATERIALS AND METHODS: Viability assays were performed on NTZ-susceptible and NTZ-resistant G. lamblia cultures in the presence of nitro-thiazole compounds, and cytotoxicity was determined in Caco-2 and HT29 cell lines. The IC50 was determined, and metabolic gene expression levels were evaluated by quantitative RT-qPCR. Finally, the ADP/ATP, NAD/NADH, and ROS ratios were determined, and ADMET parameters were predicted. RESULTS AND DISCUSSION: 120 compounds were evaluated, and a series of nitrothiazole derivatives reduced the viability of G. lamblia trophozoites by 100%. Comp-5 and Comp-3 showed 60 times greater potency than NTZ. Furthermore, they exhibited high selectivity indices and low toxicity against Caco-2 and HT29 cell lines. Compounds induce modifications in the expression profiles associated with glycolysis and energy production, consistent with a loss of balance in the ADP/ATP, NAD/NADH, and ROS ratios. Molecular docking and molecular dynamics simulations showed that the compounds exhibit affinity for five essential metabolic enzymes: PK, PPDK, PFOR, G6PD::6PGL, and Giardin. CONCLUSIONS: These findings support the proposal that Comp-3 and Comp-5 are promising candidates against giardiasis, probably exerting their action by decreasing ATP and metabolite production, which are necessary for their proliferation, with multitarget activity against drug-resistant strains. [ABSTRACT FROM AUTHOR]
Abstract (Spanish):	ANTECEDENTES: La giardiasis es una enfermedad intestinal con una creciente prevalencia de cepas de Giardia lamblia resistentes a antiparasitarios, lo que subraya la necesidad de buscar nuevos candidatos terapéuticos. OBJETIVO: Evaluar el efecto de siete compuestos nitro-tiazólicos sobre la viabilidad y el metabolismo en G. lamblia. MATERIAL Y MÉTODOS: Se realizaron ensayos de viabilidad en cultivos de G. lamblia susceptibles y resistentes a nitazoxanida (NTZ) en presencia de compuestos nitro-tiazólicos y se determinó la citotoxicidad en líneas celulares Caco-2 y HT29. Se determinó la IC50 y se evaluó los niveles de expresión de genes metabólicos mediante RT-qPCR cuantitativa. Finalmente se determinó el radio de ADP/ATP, NAD/NADH y ROS, y se predijeron los parámetros ADMET. RESULTADOS Y DISCUSIÓN: Se evaluaron 120 compuestos y se encontró una serie de derivados de nitro-tiazoles que redujeron 100% la viabilidad de trofozoítos de G. lamblia. El Comp-5 y Comp-3 mostraron una potencia 60 veces mayor a NTZ. Además, mostraron altos índices de selectividad y baja toxicidad en Caco-2 y HT29. Los Comp-3 y Comp-5 inducen modificaciones en los perfiles de expresión asociados a glucolisis y obtención de energía, lo cual concuerda con la perdida del balance del radio de ADP/ATP, NAD/NADH y ROS. El acoplamiento molecular y simulaciones de dinámica molecular mostraron que los compuestos muestran afinidad por cinco enzimas metabólicas esenciales: PK, PPDK, PFOR, G6PD::6PGL y Giardin. CONCLUSIONES: Estos hallazgos respaldan la propuesta que Comp-3 y Comp-5 son candidatos prometedores contra la giardiasis, probablemente ejercen su acción mediante una disminución en la producción de ATP y metabolitos necesarios para su proliferación, con actividad multiobjetivo contra cepas resistentes a fármacos. [ABSTRACT FROM AUTHOR]
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Database:	MedicLatina

Description
Abstract:	BACKGROUND: Giardiasis is an intestinal disease with a growing prevalence of antiparasitic-resistant strains of Giardia lamblia, underscoring the need to identify new therapeutic candidates. OBJECTIVE: Evaluate the effect of seven nitro-thiazole compounds on viability and metabolism in G. lamblia. MATERIALS AND METHODS: Viability assays were performed on NTZ-susceptible and NTZ-resistant G. lamblia cultures in the presence of nitro-thiazole compounds, and cytotoxicity was determined in Caco-2 and HT29 cell lines. The IC50 was determined, and metabolic gene expression levels were evaluated by quantitative RT-qPCR. Finally, the ADP/ATP, NAD/NADH, and ROS ratios were determined, and ADMET parameters were predicted. RESULTS AND DISCUSSION: 120 compounds were evaluated, and a series of nitrothiazole derivatives reduced the viability of G. lamblia trophozoites by 100%. Comp-5 and Comp-3 showed 60 times greater potency than NTZ. Furthermore, they exhibited high selectivity indices and low toxicity against Caco-2 and HT29 cell lines. Compounds induce modifications in the expression profiles associated with glycolysis and energy production, consistent with a loss of balance in the ADP/ATP, NAD/NADH, and ROS ratios. Molecular docking and molecular dynamics simulations showed that the compounds exhibit affinity for five essential metabolic enzymes: PK, PPDK, PFOR, G6PD::6PGL, and Giardin. CONCLUSIONS: These findings support the proposal that Comp-3 and Comp-5 are promising candidates against giardiasis, probably exerting their action by decreasing ATP and metabolite production, which are necessary for their proliferation, with multitarget activity against drug-resistant strains. [ABSTRACT FROM AUTHOR]
ISSN:	01862391
DOI:	10.18233/apm.v47i1S.3441