Enhanced Antigiardial Effect of Omeprazole Analog Benzimidazole Compounds.

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.

Linezolid diminishes inflammatory cytokine production from human peripheral blood mononuclear cells.

BACKGROUND: Active peptides produced by monocytes, in response to endotoxin, initiate and maintain the acute phase of inflammatory response. Some antibiotics have been reported to have immunomodulatory effects in addition to their antimicrobial activity. We examined the effect of linezolid on cytokine synthesis. METHODS: The modulatory effects of erythromycin and linezolid were evaluated in LPS-stimulated human peripheral blood mononuclear cells (PBMCs). Blood was obtained by venipuncture from healthy donor volunteers. PBMCs were separated by Ficoll-Paque. More than 90% of the cells were monocytes as determined by esterase staining. Cells were incubated in the presence of LPS, with or without various concentrations of erythromycin and linezolid. The concentration of each cytokine was determined by ELISA with commercially available reagents. RESULTS: The two drugs suppressed significantly the synthesis of the cytokines tested in a concentration-dependent manner. CONCLUSIONS: These data indicate that antibacterial agents may modify acute phase inflammatory response through their effects on cytokines synthesis by monocytes.