Enhanced Antigiardial Effect of Omeprazole Analog Benzimidazole Compounds

• Main Authors: Beatriz Hernández-Ochoa, Saúl Gómez-Manzo, Adrián Sánchez-Carrillo, Jaime Marcial-Quino, Luz María Rocha-Ramírez, Araceli Santos-Segura, Edson Jiovany Ramírez-Nava, Roberto Arreguin-Espinosa, Miguel Cuevas-Cruz, Alfonso Méndez-Tenorio, Ernesto Calderón-Jaimes
• Format: Article
• Language: English
• Published: MDPI AG 2020-09-01
• Series: Molecules
• Subjects: omeprazole analogs; giardiasis; inhibition enzyme; giardiacidal compounds
• Online Access: https://www.mdpi.com/1420-3049/25/17/3979

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 <i>Giardia</i>, 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, <b>H-BZM2</b>, <b>O₂N-BZM7</b>, and <b>O₂N-BZM9</b> had greater antigiardial activity (IC₅₀: 36, 14, and 17 µM on trophozoites), and inhibited the TPI enzyme (<i>K</i>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.