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We describe here the synthesis of enantiomerically pure chalcogenoethers obtained through the reaction of nucleophilic species of chalcogen (S, Se and Te), generated in situ from the respective diorganyl dichalcogenides, with (R)- and (S)-tosyl solketal. Furthermore, some of the chalcogenoethers were treated with acidic cation exchange resin Dowex-(H+) leading to the respective deprotected enantiomerically pure 3-phenylchalcogenyl-1,2-diols. In order to explore the biological potential of these molecules, the antioxidant activity of some organochalcogens was evaluated by several in vitro assays. Overall, the chalcogenoethers containing Te were better scavengers of DPPH and ABTS·+ radicals, had higher ferric reducing capacity and prevented lipid peroxidation. To analyze the effects of these compounds in vivo, we used the alternative model Caenorhabditis elegans. Chalcogenoethers treatment, especially (S)- and (R)-2,2-dimethyl-4-(phenylselanylmethyl)-1,3-dioxolane, conferred protection against the mortality-induced by hydrogen peroxide. Accordingly, these chalcogenoethers were able to modulate the antioxidant enzyme catalase. Notably, the compounds did not present toxicity in worm’s reproduction. To sum up, our study demonstrated that Te- containing chalcogenoethers were promising in vitro scavengers, while Se molecules were more prone to protect against a stressor in vivo. In this sense, the antioxidant activity of chalcogenoethers, especially with Se and Te, indicates that these molecules may have biological application in an attempt to reduce the oxidative stress. Keywords: Organochalcogen, Chiral, Chalcogenoethers, PEG-400, Antioxidant, Caenorhabditis elegans

Increased prevalence of metronidazole-resistant infections has resulted in a search for alternative drugs for the treatment of trichomoniasis. In the present study, we report the evaluation of in vitro activity of three quinolines-1,2,3-triazolylcarboxamides (QTCA-1, QTCA-2 and QTCA-3) against Trichomonas vaginalis, evaluation of cytotoxicity in CHO cells and expression of genes related to hydrogenosome by real time PCR. Nine concentrations of these compounds were analyzed for in vitro activity against ATCC 30236 isolate of T. vaginalis. QTCA-2 reported a cytotoxic effect against 100% of T. vaginalis trophozoites at a final concentration of 80 μM with an IC50 of 50 μM. The kinetic growth curve of trophozoites indicated that QTCA-2 reduced the growth by 70% at a concentration of 80 μM after an exposure of 12 h, and induced complete parasite death at 24 h. QTCA-2 induced less than 30% of cytotoxicity in CHO-K1 cells at 80 μM and data showed this concentration and lower ones had no significant cytotoxic effect when compared to the control. There was no significant difference in gene expression (pyruvate-ferredoxin oxidoreductase A and B; Malic enzyme D; Hydrogenase; β-tubulin) when compared to control and MTZ. Further in silico analysis showed that QTCA-2 had significant binding free energy with T. vaginalis lactate dehydrogenase (−9.3 kcal/mol), purine nucleoside phosphorylase (−9.1 kcal/mol) and triosephosphate isomerase (−7.3 kcal/mol). The present study offers new perspectives for exploring the potential of this class of molecules as an additional option for the treatment of trichomoniasis. Keywords: Antiparasitic, Quinolines, qRT-PCR, Molecular docking

Despite the severity and the high prevalence of depression and anxiety and the efforts that have been done to improve their treatment, the available pharmacotherapy still has several limitations. Therefore, the investigation of novel agents and the characterization of the molecular signaling pathways underlying their effects are needed. The organoselenium compound 3-[(4-chlorophenyl)selanyl]-1-methyl-1H-indole (CMI) has emerged as a promising antidepressant and anxiolytic molecule in several animal models of depression through the modulation of neuroinflammation and oxidative stress. In light of this, the present study aimed to dive into the mechanism of action of CMI in ameliorating anhedonic- and anxiogenic-like behaviors induced by repeated corticosterone administration in mice. A single administration of CMI (1 ​mg/kg, i.g.) abrogated the behavioral alterations induced by corticosterone in the open field test, splash test, and elevated plus maze test. Additionally, CMI treatment decreased the levels of reactive species and lipid peroxidation in the plasma of corticosterone-treated mice and normalized the expression of GR, BDNF, synaptophysin, GSK-3β, Nrf2, and IDO in the hippocampi of stressed mice. Noteworthy, the pre-treatment of mice with LY294002 (PI3K inhibitor) and rapamycin (mTOR inhibitor) abrogated the anti-anhedonic- and anxiolytic-like effects elicited by CMI in corticosterone-treated mice, while ZnPP (HO-1 inhibitor) counteracted the anxiolytic-like effect of CMI. These findings suggest that CMI might ameliorate behavioral and biochemical alterations in the depression-anxiety comorbidity induced by corticosterone, highlighting the potential of CMI as a possible adjuvant therapy.