TY - JOUR
T1 - Enhanced Antigiardial Effect of Omeprazole Analog Benzimidazole Compounds
AU - Hernández-Ochoa, Beatriz
AU - Gómez-Manzo, Saúl
AU - Sánchez-Carrillo, Adrián
AU - Marcial-Quino, Jaime
AU - Rocha-Ramírez, Luz María
AU - Santos-Segura, Araceli
AU - Ramírez-Nava, Edson Jiovany
AU - Arreguin-Espinosa, Roberto
AU - Cuevas-Cruz, Miguel
AU - Méndez-Tenorio, Alfonso
AU - Calderón-Jaimes, Ernesto
N1 - Publisher Copyright:
© 2020 by the authors.
PY - 2020/9
Y1 - 2020/9
N2 - 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, 1H NMR, and 13C NMR techniques. The in vitro efficacy compounds against Giardia, 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 ◦C in TE buffer, pH 7.4 with increasing concentrations of the compounds. Among the target compounds, H-BZM2, O2N-BZM7, and O2N-BZM9 had greater antigiardial activity (IC50: 36, 14, and 17 µM on trophozoites), and inhibited the TPI enzyme (K2: 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.
AB - 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, 1H NMR, and 13C NMR techniques. The in vitro efficacy compounds against Giardia, 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 ◦C in TE buffer, pH 7.4 with increasing concentrations of the compounds. Among the target compounds, H-BZM2, O2N-BZM7, and O2N-BZM9 had greater antigiardial activity (IC50: 36, 14, and 17 µM on trophozoites), and inhibited the TPI enzyme (K2: 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.
KW - Giardiacidal compounds
KW - Giardiasis
KW - Inhibition enzyme
KW - Omeprazole analogs
UR - http://www.scopus.com/inward/record.url?scp=85090320583&partnerID=8YFLogxK
U2 - 10.3390/molecules25173979
DO - 10.3390/molecules25173979
M3 - Artículo
C2 - 32882836
AN - SCOPUS:85090320583
SN - 1420-3049
VL - 25
JO - Molecules
JF - Molecules
IS - 17
M1 - 3979
ER -