期刊
MOLECULES
卷 25, 期 17, 页码 -出版社
MDPI
DOI: 10.3390/molecules25173979
关键词
omeprazole analogs; giardiasis; inhibition enzyme; giardiacidal compounds
资金
- Fondos Federales, Mexico
- E022 Program, National Institute of Pediatrics, Mexico City, Mexico (Recursos Fiscales para la Investigacion)
- INP [038/2019, 024/2017]
- CONACYT [259201]
- Catedras CONACYT [2184, 2057]
- [HIM/2017/100 SSA 1430]
- [HIM/2014/013 SSA 1120]
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.
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