Enhanced Antigiardial Effect of Omeprazole Analog Benzimidazole Compounds

• Published in: Molecules (Basel, Switzerland) Vol. 25; no. 17; p. 3979
• Main Authors: Hernández-Ochoa, Beatriz, Gómez-Manzo, Saúl, Sánchez-Carrillo, Adrián, Marcial-Quino, Jaime, Rocha-Ramírez, Luz María, Santos-Segura, Araceli, Ramírez-Nava, Edson Jiovany, Arreguin-Espinosa, Roberto, Cuevas-Cruz, Miguel, Méndez-Tenorio, Alfonso, Calderón-Jaimes, Ernesto
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 01.09.2020; MDPI
• Subjects: Antiprotozoal Agents - chemical synthesis; Antiprotozoal Agents - chemistry; Antiprotozoal Agents - pharmacology; Benzimidazoles; Benzimidazoles - chemical synthesis; Benzimidazoles - chemistry; Benzimidazoles - pharmacology; Caco-2 Cells; Cell Death - drug effects; Cell Survival - drug effects; Chromatography; Circular Dichroism; Cytotoxicity; Developing countries; Diarrhea; Disease; Drug Design; Drug dosages; Drug Evaluation, Preclinical; Drug therapy; Drugs; Enzyme Activation - drug effects; Enzymes; Giardia lamblia - drug effects; Giardia lamblia - enzymology; giardiacidal compounds; Giardiasis; HT29 Cells; Humans; Inactivation; inhibition enzyme; Kinetics; Lansoprazole - pharmacology; LDCs; Molecular Docking Simulation; Omeprazole; Omeprazole - chemical synthesis; Omeprazole - chemistry; Omeprazole - pharmacology; omeprazole analogs; Parasites; Parasitic diseases; Protein structure; Secondary structure; Spectrometry, Fluorescence; Structural stability; Tertiary structure; Toxicity; Triose-phosphate isomerase; Triose-Phosphate Isomerase - antagonists & inhibitors; Triose-Phosphate Isomerase - chemistry; Trophozoites; Trophozoites - drug effects; Tropical diseases; inhibition enzyme; giardiasis; giardiacidal compounds; omeprazole analogs
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules25173979

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 NMR, and C NMR techniques. The in vitro efficacy compounds against , 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, , , and had greater antigiardial activity (IC : 36, 14, and 17 µM on trophozoites), and inhibited the TPI enzyme ( : 2.3, 3.2, and 2.8 M s ) 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.