Ovicidal activity of diaryl dichalcogenides and ivermectin on Fasciola hepatica: A novel candidate for a blending-based therapeutic strategy.

Fasciolosis is a food and waterborne disease caused by Fasciola spp., representing a global health burden to various hosts, including humans and other animals. This study investigates the in vitro activity of tellurium- and selenium-containing diaryl dichalcogenides: diacetal ditelluride (LQ07), diacetal diselenide (LQ62), and diacetyl diselenide (LQ68) alone and in combination with ivermectin (IVM) against eggs of Fasciola hepatica. The eggs were exposed for 12 h with each organochalcogen (OC) (0.1 - 2 mmol l-1) and IVM (0.01 - 2 mmol l-1) following an incubation of 15 days, allowing embryonation. The inhibitory concentration of 50 % (IC50) of each OC or IVM was tested with the IC10, IC30, and IC50 of IVM or each OC, respectively. LQ07, LQ62, and LQ68, as well as IVM, demonstrated a concentration-dependent ovicidal activity. The peak ovicidal activity of 99.74 % was achieved when IVM was tested at 2.0 mmol l-1. LQ62 and LQ68 demonstrated greater ovicidal activity, having an IC50 < 0.32 mmol l-1 being 6.25-fold more toxic than IVM alone. The percentage of dead eggs was significantly higher in the IVM group (early mortality), as Se-containing OCs led to the (miracidia) embryonation of the eggs with no hatching (late mortality). Blending Se-containing OCs and IVM showed an additive effect of up to 27 % against F. hepatica eggs. The present data contribute to the potential use of blending-based therapeutic strategies to combat F. hepatica infections in eradication programs worldwide. The combinations may also act against multidrug-resistant strains, reinstating drug-based parasite control.

(PhSe)2 and (pCl-PhSe)2 organochalcogen compounds inhibit Candida albicans adhesion to human endocervical (HeLa) cells and show anti-biofilm activities.

Adhesion capacity on biological surfaces and biofilm formation is considered an important step in the infection process by Candida albicans. The ability of (PhSe)2 and (pCl-PhSe)2, two synthetic organic selenium (organochalcogen) compounds, to act on C. albicans virulence factors related to adhesion to human endocervical (HeLa) cell surfaces and their anti-biofilm activities was analyzed. Both organochalcogen compounds inhibited C. albicans adhesion to HeLa cells, dependent on compound concentrations. (PhSe)2 (at 20 µM; p = 0.0012) was significantly more effective than (pCl-PhSe)2 (at 20 µM; p = 0.0183) compared with the control. (PhSe)2 inhibited biofilm formation and decreased biofilm viability in both early and mature biofilms more efficiently than (pCl-PhSe)2. Overall, the organochalcogen compounds, especially (PhSe)2, were demonstrated to be effective antifungal drugs against C. albicans virulence factors related to epithelial cell surface adhesion and the formation and viability of biofilms.

The Organochalcogen Compound (MeOPhSe)2 Inhibits Both Formation and the Viability of the Biofilm Produced by Candida albicans, at Different Stages of Development.

BACKGROUND: Candida albicans is a commensal and opportunistic fungus which is able to produce both local and systemic infections in immunocompromised patients. A correlation has been demonstrated between the resistance to conventional antifungal drugs and C. albicans ability to produce biofilms. Therefore, the potential of the organochalcogen compounds as antifungal therapy has been demonstrated. METHOD: In this work, we studied the effect of the organochalcogen compound (MeOPhSe)2 on both formation and the viability of the biofilm produced by C. albicans, at different stages of development. Biofilm formation and viability were determined by a metabolic assay based on the reduction of XTT assay. In addition, the morphology of the biofilm was observed using light microscopy. RESULTS: A significant reduction was observed in both growth and biofilm formation by C. albicans, in a dependent manner of cell density. In the presence of 2 µM (MeOPhSe)2 it was observed an inhibition of 87, 72, 69 and 56 % in C. albicans growth, using cell densities of 104, 105, 106 and 107 cells/mL, respectively. C. albicans growth was inhibited >90 % in the presence of 10 µM (MeOPhSe)2 in all cell densities used. Also, (MeOPhSe)2 was found to be able to decrease the viability of the biofilm produced by C. albicans at different stages of development. This effect was more pronounced in early biofilms as compared to mature biofilms. Biofilms forming at 6 and 12 hours was inhibited ~80% in the presence of 10 µM (MeOPhSe)2. However, mature biofilms presented an inhibition of ~40 % in the presence of 10 µM (MeOPhSe)2. The analyses of the structure of the biofilm have shown a significant reduction in the number of both yeast and filamentous form after treatment with (MeOPhSe)2. In addition, the organochalcogen compound (MeOPhSe)2 did not modify the viability of Fibroblastic cells. CONCLUSION: Taken together, these results demonstrated the potential of the organochalcogen compound (MeOPhSe) 2 as a promising antifungal therapy.

Organochalcogen compounds from glycerol: synthesis of new antioxidants.

We describe here a simple method for the synthesis of glycerol derivatives containing an organochalcogen unit (Se, Te and S) using NaBH4 and PEG-400 as a solvent. The new methodology was used to synthesize a range of new organochalcogen compounds in good yields. Furthermore, four of synthesized compounds were evaluated for their antioxidant activity using different assays, such as 2-azinobis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS), 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical, nitric oxide (NO) and hydroxyl radical (OH) scavenging, ferric ion reducing antioxidant power (FRAP), ferrous ion chelating, superoxide dismutase-like activity and inhibition of linoleic acid lipid peroxidation. The new organotellurium 2,2-dimethyl-4-(phenyltellanylmethyl)-1,3-dioxolane 3 j showed antioxidant activity and was more effective in inhibition of induced lipid peroxidation compared to solketal 4. Selenium and sulfur analogs 3a and 3m and solketal 4 did not present antioxidant effect. These findings suggest that 2,2-dimethyl-4-(phenyltellanylmethyl)-1,3-dioxolane 3 j is a promising antioxidant and that its activity is influenced by the presence of the tellurium atom on the structure.