Altg Ruiz

Evaluation of the antioxidant and antiproliferative potential of bioflavors

α-Terpineol is a relatively cheap and abundant aroma compound. It is widely used in food, cosmetics, and household products. Many of its monoterpene counterparts have been applied in antiproliferative assays, leading to promising results in the prevention or even treatment of cancers. However, despite its theoretic potential, no paper reports the evaluation of antiproliferative capacity of this alcohol. Thus, antioxidant potential of three monoterpenoids (carvone, perillyl alcohol, and α-terpineol) was measured using two methods: DPPH and ORAC. Also, the antiproliferative effect of these monoterpenoids against nine cancerous cell lines were performed and compared to limonene and doxorubicin. Results showed that all samples tested had very low antioxidant activity in the DPPH assay, but α-terpineol (2.72μmolTrolox equiv./μmol) could be compared to commercial antioxidants in the ORAC assay. The antiproliferative results obtained encourage future in vivo studies for α-terpineol, since this monoterpenoid presented cytostatic effect against six cell lines, especially for breast adenocarcinoma and chronic myeloid leukemia, in a range of 181-588μM.

Hydroxyaldimines as potent in vitro anticryptococcal agents.

Cryptococcosis, a fungal infection that affects both immunocompromised and immunocompetent individuals, contributes to increasing indices of mortality and morbidity. The development of resistance by Cryptococcus spp., the limited number of commercial antifungal drugs and the various side effects of these drugs cause the treatment of cryptococcosis to be a challenge. The in vitro anticryptococcal activity of nine hydroxyaldimines was evaluated against 24 strains of Cryptococcus spp. Antifungal susceptibility was evaluated using a broth microdilution assay following the Clinical and Laboratory Standards Institute guidelines, using fluconazole as a positive control. Parameters such as the minimum inhibitory concentration and the minimum fungicidal concentration (MIC and MFC, respectively) were also determined. Antiproliferative activity on the normal cell line VERO was assessed 48 h post‐compound exposure to determine the selectivity index (SI) of the hydroxyaldimines and fluconazole. All hydroxyaldimines were active against Cryptococcus spp. strains. Compounds 3A9 and 3B7 were the most potent against the Cryptococcus gattii and Cryptococcus neoformans strains. Selectivity indices also revealed that 3B10, 3C3, 3D3 and 3D9 are good candidates for in vivo studies. The in vitro anticryptococcal activity of hydroxyaldimines against various strains of C. gattii and C. neoformans indicates the potential of this class of molecules as lead compound for the development of selective and efficient anticryptococcal agents.

Avaliação do potencial alelopático, atividade antimicrobiana e antioxidante dos extratos orgânicos das folhas de Pyrostegia venusta (Ker Gawl.) Miers (Bignoniaceae)

This paper presents the results of allelopathic, antimicrobial and antioxidant activities of organic extracts (hexane, ethyl acetate and methanol) from the leaves of Pyrostegia venusta (Ker Gawl.) Miers (Bignoniaceae). Allelopathic activity was assessed based on Cucumis sativus (cucumber) development for the parameters main root length, number of secondary roots and hypocotyl length. All tested extracts affected the first two parameters, while the hypocotyl length was not affected only by the ethyl acetate extract. For antimicrobial activity, assessed by MIC assay, hexane extract showed moderate inhibition for Staphylococcus aureus (0.9 mg mL-1) and strong inhibition for Enterococcus hirae (0.5 mg mL-1). Ethyl acetate extract showed strong activity against Candida albicans (0.3 mg mL-1), whereas methanolic extract was not active against the tested microorganisms. On the other hand, methanol extract showed the most promising radical scavenging capacity (Effective Concentration 50% - EC50 = 102.0 ± 56.9 mg mL-1, with TEC50 = 30 min) in DPPH assay (2,2-diphenyl-1-picryl-hidrazil) and the highest level of phenolic compounds (116.2 ± 83.0 mg acid garlic g sample-1), as indicated by Folin-Ciocalteau assay.

Profiles of phenolic compounds by FT-ICR MS and antioxidative and antiproliferative activities of Stryphnodendron obovatum Benth leaf extracts

Stryphnodendron obovatum Benth is a Brazilian Cerrado tree, which is rich in catechin derivatives, being therefore widely used in folk medicine. Its seeds, beans and bark have been used for various medicinal purposes, but few reports have tried to correlate their biological activity with their chemical composition. In this study, we have profiled the main phenolic constituents of S. obovatum leaf extracts by ultrahigh resolution mass spectrometry (FT-ICR MS), and tried to establish a correlation of metabolites and antioxidant and in vitro antiproliferative activities. In the methanolic extract flavonoid derivatives were detected and they presented the most promising scavenging activities for methanolic extracts (EC50 0.86 ± 0.01 μg mL−1), being slightly more active than Trolox (EC50 1.13 ± 0.09 μg mL−1). In the hydroethanolic extract, catechin derivatives as well as protocatechuic acid-glucoside were detected and found to be a little less active than the control (EC50 1.39 ± 0.01 μg mL−1). The best performance in terms of antiproliferative activity was found for the methanolic extract for renal cell lines (TGI 40.6 g mL−1).

Linear gold(I) complex with tris-(2-carboxyethyl)phosphine (TCEP): Selective antitumor activity and inertness toward sulfur proteins

The search for modulating ligand substitution reaction in gold complexes is essential to find new active metallo compounds for medical applications. In this work, a new linear and hydrosoluble goldI complex with tris-(2-carboxyethylphosphine) (AuTCEP). The two phosphines coordinate linearly to the metal as solved by single crystal X-ray diffraction. Complete spectroscopic characterization is also reported. In vitro growth inhibition (GI50) in a panel of nine tumorigenic and one non-tumorigenic cell lines demonstrated the complex is highly selective to ovarium adenocarcinoma (OVCAR-03) with GI50 of 3.04 nmol mL-1. Moreover, non-differential uptake of AuTCEP was observed between OVCAR-03 (tumor) and HaCaT (non-tumor) two cell lines. Biophysical evaluation with the sulfur-rich biomolecules showed the compound does not interact with two types of zinc fingers, bovine serum albumin, N-acetyl-l-cysteine and also l-histidine, revealing to be inert to ligand substitution reactions with these molecules. However, AuTCEP demonstrated to cleave plasmidial DNA, suggesting DNA as a possible target. No antibacterial activity was observed in the strains evaluated. Besides, it inhibits 15% of the activity of a mixture of serine-β-lactamase and metallo-β-lactamase from Bacillus cereus in the enzymatic activity assay, similarly to EDTA. These results suggest AuTCEP is selective to metallo-β-lactamase but the cell uptake is hindered, and the compound does not reach the periplasmic space of Gram-positive bacteria. The unique inert behavior of AuTCEP is interesting and represent the modulation of the reactivity through coordination chemistry to decrease the toxicity associated with AuI complexes and its lack of specificity, generating very selective compounds with unexpected targets.