Effects of bioconversion by Battus polydamas on the chemical composition of Aristolochia spp. and evaluation of antimicrobial activity and biocompatibility.

Aristolochia plants are emblematic from an ethnopharmacological viewpoint and are know to possess numerous biological properties, including antiseptic. However, the medicinal potential of these species is debatable because of their representative chemical constituents, aristolochic acids (AAs) and aristolactams (ALs), which are associated, for instance, with nephropathy and cancer. These contrasting issues have stimulated the development of approaches intended to detoxification of aristoloquiaceous biomasses, among which is included the bioconversion method using larvae of the specialist phytophagous insect Battus polydamas, previously shown to be viable for chemical diversification and to reduce toxicity. Thus, eleven Aristolochia spp. were bioconverted, and the antimicrobial activities of the plant methanolic extracts and its respective bioconversion products were evaluated. The best results were found for Aristolochia esperanzae, Aristolochia gibertii, and Aristolochia ringens against Bacillus cereus, with MIC ranging from 7.8 to 31.25 µg/mL. These three species were selected for chemical, antioxidant, cytotoxic, hemolytic, and mutagenic analyses. Chemical analysis revealed 65 compounds, 21 of them possible bioconversion products. The extracts showed potential to inhibit the formation and degradation of B. cereus biofilms. Extracts of A. gibertii and its bioconverted biomass showed antioxidant activity comparable to dibutylhydroxytoluene (BHT) standard. Bioconversion decreased the hemolytic activity of A. esperanzae and the cytotoxicities of A. esperanzae and A. gibertii. None of the extracts was found to be mutagenic. The bioactivities of the fecal extracts were maintained, and biocompatibility was improved. Therefore, the results obtained in this study reveal positive expectations about the natural detoxification process of the Aristolochia species.

Design and Synthesis of Novel 3-Nitro-1H-1,2,4-triazole-1,2,3-triazole-1,4-disubstituted Analogs as Promising Antitrypanosomatid Agents: Evaluation of In Vitro Activity against Chagas Disease and Leishmaniasis.

A series of 28 compounds, 3-nitro-1H-1,2,4-triazole, were synthesized by click-chemistry with diverse substitution patterns using medicinal chemistry approaches, such as bioisosterism, Craig-plot, and the Topliss set with excellent yields. Overall, the analogs demonstrated relevant in vitro antitrypanosomatid activity. Analog 15g (R1 = 4-OCF3-Ph, IC50 = 0.09 µM, SI = >555.5) exhibited an outstanding antichagasic activity (Trypanosoma cruzi, Tulahuen LacZ strain) 68-fold more active than benznidazole (BZN, IC50 = 6.15 µM, SI = >8.13) with relevant selectivity index, and suitable LipE = 5.31. 15g was considered an appropriate substrate for the type I nitro reductases (TcNTR I), contributing to a likely potential mechanism of action for antichagasic activity. Finally, 15g showed nonmutagenic potential against Salmonella typhimurium strains (TA98, TA100, and TA102). Therefore, 3-nitro-1H-1,2,4-triazole 15g is a promising antitrypanosomatid candidate for in vivo studies.

Chemical composition and effects of ethanolic extract and gel of Cochlospermum regium (Schrank) Pilg. Leaves on inflammation, pain, and wounds.

ETHNOPHARMACOLOGICAL RELEVANCE: Cochlospermum regium is well-known as "Algodãozinho do cerrado" in folk Brazilian medicine, and is used to fight infections, inflammation and skin disorders. AIM OF THE STUDY: To identify the phytochemical constituents and the effects of the ethanolic extract of C. regium leaves (EECR) on inflammation and pain, and the effects of C. regium gel (GEECR) on wound healing. MATERIALS AND METHODS: Animals were treated with EECR (30-300 mg/kg) or GEECR (1.25 and 2.5%) and studies were conducted using carrageenan-induced pleurisy and paw edema tests, formalin-induced pain model, and excision wound model. RESULTS: In total, 25 compounds, including quercitrin, methyl gallate, and 1,2,3,4,6-pentagalloylhexose, with highest detectability were identified. The treatments reduced leukocyte migration, nitric oxide production, protein extravasation, edema, mechanical hyperalgesia, pain in both phases (neurogenic and inflammatory), cold hypersensitivity, and improved wound closure and tissue regeneration. CONCLUSIONS: The present findings established the anti-inflammatory, anti-nociceptive, and wound healing potential of the leaves of C. regium, confirming the potential therapeutic effect of this plant.

Cytotoxicity, mutagenicity and acute oral toxicity of aqueous Ocotea minarum leaf extracts.

Ocotea minarum (Nees & Mart.) Mez., a native species of Brazil, is used in the treatment of infections and oxidative stress; however, there is no scientific evidence of its toxicological characteristics. We assessed the cytotoxicity, mutagenic activity, and acute oral toxicity of the aqueous extract isolated from O. minarum leaves. The cytotoxicity of this extract was evaluated in tumour and non-tumour cell lines, while the Ames test with a Salmonella Typhimurium was used to determine the mutagenic activity. Wistar rats received a single 2 g/kg dose as part of an LD50 toxicity assessment. Our results showed that the aqueous extract of O. minarum leaves did not present cytotoxic and mutagenic properties and was not toxic, with an LD50 greater than 2 g/kg. Therefore, the O. minarum extracts are pharmacologically safe and can continue to be investigated for the development of new drugs and herbal medicines.

Prevalência e fatores de risco para retinopatia diabética em pacientes diabéticos atendidos por demanda espontânea: um estudo transversal / Prevalence and risk factors of diabetic retinopathy in patients with diabetes seen by unscheduled demand: a cross-sectional study

RESUMO Objetivo: Estimar a prevalência da retinopatia diabética em pacientes diabéticos de uma capital brasileira e correlacioná-la com fatores de risco presentes na população estudada. Métodos: Estudo observacional transversal, realizado a partir do relatório de atendimentos prestados em mutirão ocorrido em 2018. O relatório foi preenchido pelos médicos oftalmologistas durante a campanha, com informações referentes a sexo do paciente, idade, classificação do diabetes mellitus, tempo de doença, uso de insulina, índice de massa corporal, hábitos de vida (tabagismo e atividade física) e história de hipertensão arterial sistêmica, dislipidemia, infarto agudo do miocárdio e acidente vascular cerebral, além de exame clínico oftalmológico realizado na ação. Resultados: Dentre os 219 participantes do estudo, a prevalência da retinopatia diabética foi de 31,96%. As variáveis que se apresentaram como fator de risco com significância estatística foram sexo masculino, idade de 51 a 70 anos, mais de 10 anos de diabetes mellitus, insulinoterapia, índice de massa corporal ≥40kg/m2 e história prévia de infarto agudo do miocárdio. Atividade física mostrou-se como fator protetor significativo. Conclusão: Estudos populacionais ao longo dos anos comprovaram a variabilidade geográfica na prevalência da retinopatia diabética justificada pela diferente exposição aos fatores de risco. Dentro de tal conjuntura, ressalta-se o quão fundamental é o conhecimento das características regionais, de modo a orientar as políticas de saúde pública, permitindo atuar com impacto na redução das estatísticas de cegueira evitável.

ABSTRACT Objective: To estimate the prevalence of diabetic retinopathy in patients with diabetes, from a Brazilian capital city, and to correlate with the risk factors present in the studied population. Methods: A cross-sectional observational study, based on the report of care provided by a campaign, in 2018. The report was filled out by ophthalmologists during the joint effort, with information on patient's gender, age, classification of diabetes mellitus, duration of illness, use of insulin, body mass index, lifestyle (smoking and physical activity), history of hypertension, dyslipidemia, myocardial infarction, stroke, and the clinical ophthalmic examination. Results: Among the 219 study participants, the prevalence of diabetic retinopathy was 31.96%. The variables considered risk factors with statistical significance were male sex, age 51-70 years, diabetes mellitus for over 10 years, insulin therapy, body mass index ≥40 kg/m2, and previous history of myocardial infarction. The physical activity proved to be a significant protective factor. Conclusion: Over the years, population studies have proven the geographical variability in prevalence of diabetic retinopathy justified by different exposure to risk factors. Therefore, knowledge of regional characteristics is crucial and emphasized in the text, since it can guide public health policies, aiming to have an impact on reduction of preventable blindness statistics.

Synthesis, structural characterization, and prospects for new cobalt (II) complexes with thiocarbamoyl-pyrazoline ligands as promising antifungal agents.

Candida spp. cause invasive fungal infections. One species, Candida glabrata, may present intrinsic resistance to conventional antifungal agents, thereby increasing mortality rates in hospitalized patients. In this context, metal complexes present an alternative for the development of new antifungal drugs owing to their biological and pharmacological activities demonstrated in studies in the last decades. Accordingly, in this study we have synthesized and characterized two new Co(II) complexes with thiocarbamoyl-pyrazoline ligands to assess their antimicrobial, mutagenic, and cytotoxic potential. For antimicrobial activity, the broth microdilution method was performed against ATCC strains of Candida spp. and fluconazole dose-dependent isolates of C. glabrata obtained from urine samples. The Ames test was used to assess mutagenic potential. The reduction method of the MTS reagent (3 [4,5-dimethylthiazol-2-yl]-5-[3-carboxymethoxyphenyl]-2-[4-sulfophenyl]-2H-tetrazolium) was performed with HeLa, SiHa, and Vero cells to determine cytotoxicity. Both complexes exhibited fungistatic and fungicidal activity for the yeasts used in the study, demonstrating greater potential for C. glabrata ATCC 2001 and the C. glabrata CG66 isolate with a Minimum Inhibitory Concentration MIC from 3.90 to 7.81 µg mL-1 and fungicidal action from 7.81 to 15.62 µg mL-1. The complexes inhibited and degraded biofilms by up to 90% and did not present mutagenic and cytotoxic potential at the concentrations evaluated for MIC. Thus, the complexes examined herein suggest promising alternatives for the development of new antifungal drugs.

Cochlospermum regium (Schrank) pilger leaf extract inhibit methicillin-resistant Staphylococcus aureus biofilm formation.

ETHNOPHARMACOLOGICAL RELEVANCE: Cochlospermum regium, known as "algodãozinho", is an important plant belonging to Brazilian biodiversity used in traditional medicine to treat infections, wounds and skin conditions. AIM OF THE STUDY: To assess the effects of aqueous and ethanolic extracts from C. regium leaves on methicillin-resistant Staphylococcus aureus planktonic cells and biofilm formation. MATERIAL AND METHODS: The phytochemical characterization of the extracts was carried out by quantification of flavonoids, phenols and tannins and HPLC-DAD. Minimum inhibitory concentrations, cell viability, and enzyme activity inhibition were determined in planktonic cells exposed to C. regium extracts. The effect of the extracts on biofilms was assessed by quantifying colony-forming units (CFUs) and the extracellular matrix, and by visualizing the biofilm structure using scanning electron microscopy. RESULTS: Leaf extract contents showed high concentration of phenols and the gallic and ellagic acids were identified. The extracts showed potent antimicrobial activities at concentrations ranging from 62.5-250 µg/mL, and decreased coagulase activity. In addition, the extracts prevented biofilm formation, and the aqueous extract completely inhibited its formation. CONCLUSIONS: C. regium extracts stand out as promising alternative treatments for the prevention and treatment of methicillin-resistant Staphylococcus aureus infections.

Optimization and validation of ultrasound-assisted extraction for the determination of micro and macro minerals in non-centrifugal sugar by F AAS.

In this work, the ultrasound-assisted extraction was employed for the first time as a sample treatment in the determination of Mn, Zn, Fe, Mg and Ca in non-centrifugal sugar by F AAS. Parameters that influence the extraction, such as composition of the extraction solvent, sample mass and sonication time were optimized in this work. The optimum condition for the extraction was the proportion of 60:40% (v/v) of HNO3:H2O2 as an extraction solution, 0.100 g of non-centrifugal sugar and 60 min of sonication. Analytical curves were built in an aqueous solution. Low quantification limits for Mn (0.021), Zn (0.008), Fe (0.030), Ca (0.389) and Mg (0.009) mg L-1 were determined, suggesting a good detectability of the methodology. Estimates of repeatability and intermediate precision demonstrated that the precision observed was within the limits recommended in the literature. Good accuracy of the method was verified through the high recovery rates (91-108%).

Influence of water limitation on the competitive interaction between two Cerrado species and the invasive grass Brachiaria brizantha cv. Piatã.

Invasive grasses inhibit the growth of other plant species, and water deficit is one of the major competition problems for native vegetation. We evaluated whether the presence of Brachiaria brizantha cv. Piatã has a negative influence on the competition for water and nutrients between Anadenanthera macrocarpa and Anadenanthera colubrina (Angico species). The interspecific competition was evaluated using a randomized experimental design with the following treatments: 1) free competition (FC), in which the native species were cultivated without the grass presence and 2) under competition (UC), in which the native species grew together with the invasive grass for 120 days. We analysed the water relationships in the two species, the effect of water limitation on the antioxidant stress, the nutritional content of shoots and roots, the relative competition intensity (RCI) and growth. The presence of Piatã grass reduced the soil moisture causing a decrease of 21.9% and 29.5% in the relative water content (RWC) of leaves for A. macrocarpa and A. colubrina, respectively. For the two Angico species, the quantum efficiency of Photosystem II (ΦPSII) decreased with reduction of RWC leaf, resulting in the H2O2 increase (57.5% at day 30 for A. colubrina and 38.8% at day 120 for A. macrocarpa). The oxidative stress was evidenced by the increase in the superoxide dismutase (SOD), catalase (CAT) and ascorbate peroxidase (APX) activities in leaves and roots of both young native trees. In the UC treatment, reductions in water uptake also led to a decrease in root absorption of N, P, K, a Mg and low transport of these nutrients to the leaves of both Angico species. A. macrocarpa and A. colubrina showed less growth caused by limitation of water uptake, but the joint activity of the physiological and biochemical adjustments provided competitive ability.

A Promising Copper(II) Complex as Antifungal and Antibiofilm Drug against Yeast Infection.

The high mortality rate of candidemia and the limited option for the treatment of Candida spp. infection have been driving the search for new molecules with antifungal property. In this context, coordination complexes of metal ions and ligands appear to be important. Therefore, this study aimed to synthesize two new copper(II) complexes with 2-thiouracil and 6-methyl-2-thiouracil ligands and to evaluate their mutagenic potential and antifungal activity against Candida. The complexes were synthesized and characterized by infrared vibrational spectroscopy, CHN elemental analysis, UV-Vis experiments and ESI-HRMS spectrometry studies. The antifungal activity was evaluated by broth microdilution against 21 clinical isolates of Candida species. The mutagenic potential was evaluated by the Ames test. The complexes were Cu(Bipy)Cl2(thiouracil) (Complex 1) and Cu(Bipy)Cl2(6-methylthiouracil) (Complex 2). Complex 1 showed fungicidal and fungistatic activities against all isolates. Furthermore, the Minimum Inhibitory Concentration (MIC) from 31 to 125 µg/mL and inhibition percentage of 9.9% against the biofilms of C. krusei and C. glabrata were demonstrated. At the concentrations tested, complex 1 exhibited no mutagenic potential. Complex 2 and the free ligands exhibited no antifungal activity at the concentrations evaluated. Since complex 1 presented antifungal activity against all the tested isolates and no mutagenic potential, it could be proposed as a potential new drug for anti-Candida therapy.