Enhanced Antigiardial Effect of Omeprazole Analog Benzimidazole Compounds
Por:
Hernandez-Ochoa, Beatriz, Gomez-Manzo, Saul, Sanchez-Carrillo, Adrian, Marcial-Quino, Jaime, Maria Rocha-Ramirez, Luz, Santos-Segura, Araceli, Jiovany Ramirez-Nava, Edson, Arreguin-Espinosa, Roberto, Cuevas-Cruz, Miguel, Mendez-Tenorio, Alfonso, Calderon-Jaimes, Ernesto
Publicada:
1 sep 2020
Resumen:
Giardiasis is a diarrheal disease that is highly prevalent in developing
countries. Several drugs are available for the treatment of this
parasitosis; however, failures in drug therapy are common, and have
adverse effects and increased resistance of the parasite to the drug,
generating the need to find new alternative treatments. In this study,
we synthesized a series of 2-mercaptobenzimidazoles that are derivatives
of omeprazole, and the chemical structures were confirmed through
mass,H-1 NMR, and(13)C NMR techniques. The in vitro efficacy compounds
againstGiardia, as well as its effect on the inhibition of
triosephosphate isomerase (TPI) recombinant, were investigated, the
inactivation assays were performed with 0.2 mg/mL of the enzyme
incubating for 2 h at 37 degrees C in TE buffer, pH 7.4 with increasing
concentrations of the compounds. Among the target
compounds,H-BZM2,O2N-BZM7, andO(2)N-BZM9had greater antigiardial
activity (IC50: 36, 14, and 17 mu M on trophozoites), and inhibited the
TPI enzyme (K-2: 2.3, 3.2, and 2.8 M(-1)s(-1)) respectively, loading
alterations on the secondary structure, global stability, and tertiary
structure of the TPI protein. Finally, we demonstrated that it had low
toxicity on Caco-2 and HT29 cells. This finding makes it an attractive
potential starting point for new antigiardial drugs.
Filiaciones:
Hernandez-Ochoa, Beatriz:
Hosp Infantil Mexico Dr Federico Gomez, Lab Inmunoquim, Secretaria Salud, Ciudad De Mexico 06720, Mexico
Gomez-Manzo, Saul:
Inst Nacl Pediat, Lab Bioquim Genet, Secretaria Salud, Ciudad De Mexico 04530, Mexico
Sanchez-Carrillo, Adrian:
Hosp Infantil Mexico Dr Federico Gomez, Lab Inmunoquim, Secretaria Salud, Ciudad De Mexico 06720, Mexico
Marcial-Quino, Jaime:
Consejo Nacl Ciencia & Tecnol CONACYT, Secretaria Salud, Inst Nacl Pediat, Ciudad De Mexico 04530, Mexico
Maria Rocha-Ramirez, Luz:
Hosp Infantil Mexico Dr Federico Gomez, Unidad Invest Enfermedades Infecciosas, Secretaria Salud Dr Marquez 162, Ciudad De Mexico 06720, Mexico
Santos-Segura, Araceli:
Hosp Infantil Mexico Dr Federico Gomez, Lab Inmunoquim, Secretaria Salud, Ciudad De Mexico 06720, Mexico
Jiovany Ramirez-Nava, Edson:
Inst Nacl Pediat, Lab Bioquim Genet, Secretaria Salud, Ciudad De Mexico 04530, Mexico
Arreguin-Espinosa, Roberto:
Univ Nacl Autonoma Mexico, Inst Quim, Dept Quim Biomacromol, Ciudad De Mexico 04510, Mexico
Cuevas-Cruz, Miguel:
Univ Nacl Autonoma Mexico, Inst Quim, Dept Quim Biomacromol, Ciudad De Mexico 04510, Mexico
Mendez-Tenorio, Alfonso:
Inst Politecn Nacl, Lab Biotecnol & Bioinformat Genom, Escuela Nacl Ciencias Biol, Ciudad De Mexico 11340, Mexico
Calderon-Jaimes, Ernesto:
Hosp Infantil Mexico Dr Federico Gomez, Lab Inmunoquim, Secretaria Salud, Ciudad De Mexico 06720, Mexico
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