Enhanced Antigiardial Effect of Omeprazole Analog Benzimidazole Compounds
| Autor: | Ernesto Calderón-Jaimes, Edson Jiovany Ramírez-Nava, Beatriz Hernández-Ochoa, Saúl Gómez-Manzo, Jaime Marcial-Quino, Roberto Arreguín-Espinosa, Alfonso Méndez-Tenorio, Miguel Cuevas-Cruz, Luz María Rocha-Ramírez, Araceli Santos-Segura, Adrián Sánchez-Carrillo |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Drug Evaluation
Preclinical Pharmaceutical Science Pharmacology Analytical Chemistry Triosephosphate isomerase chemistry.chemical_compound Drug Discovery Omeprazole media_common chemistry.chemical_classification omeprazole analogs 0303 health sciences Cell Death Circular Dichroism inhibition enzyme Molecular Docking Simulation Chemistry (miscellaneous) Molecular Medicine HT29 Cells medicine.drug Triose-Phosphate Isomerase Drug Benzimidazole Cell Survival media_common.quotation_subject Antiprotozoal Agents macromolecular substances Article lcsh:QD241-441 03 medical and health sciences lcsh:Organic chemistry medicine Humans Lansoprazole Trophozoites giardiacidal compounds Physical and Theoretical Chemistry TE buffer IC50 030304 developmental biology 030306 microbiology Organic Chemistry In vitro Enzyme Activation Kinetics giardiasis Enzyme Spectrometry Fluorescence chemistry Drug Design Benzimidazoles Caco-2 Cells Giardia lamblia |
| Zdroj: | Molecules Volume 25 Issue 17 Molecules, Vol 25, Iss 3979, p 3979 (2020) |
| ISSN: | 1420-3049 |
| Popis: | 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 µ M on trophozoites), and inhibited the TPI enzyme (K2: 2.3, 3.2, and 2.8 M&minus 1 s&minus 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|