This study is the first phytochemical investigation of Selaginella sellowii and demonstrates the antileishmanial activity of the hydroethanolic extract from this plant (SSHE), as well as of the biflavonoids amentoflavone and robustaflavone, isolated from this species. The effects of these substances were evaluated on intracellular amastigotes of Leishmania (Leishmania) amazonensis, an aetiological agent of American cutaneous leishmaniasis. SSHE was highly active against intracellular amastigotes [the half maximum inhibitory concentration (IC50) = 20.2 µg/mL]. Fractionation of the extract led to the isolation of the two bioflavonoids with the highest activity: amentoflavone, which was about 200 times more active (IC50 = 0.1 μg/mL) and less cytotoxic than SSHE (IC50 = 2.2 and 3 μg/mL, respectively on NIH/3T3 and J774.A1 cells), with a high selectivity index (SI) (22 and 30), robustaflavone, which was also active against L. amazonensis (IC50 = 2.8 µg/mL), but more cytotoxic, with IC50 = 25.5 µg/mL (SI = 9.1) on NIH/3T3 cells and IC50 = 3.1 µg/mL (SI = 1.1) on J774.A1 cells. The production of nitric oxide (NO) was lower in cells treated with amentoflavone (suggesting that NO does not contribute to the leishmanicidal mechanism in this case), while NO release was higher after treatment with robustaflavone. S. sellowii may be a potential source of biflavonoids that could provide promising compounds for the treatment of cutaneous leishmaniasis.

Sixteen 1,4-diaryl-1,2,3-triazole compounds 4-19 derived from the tetrahydrofuran neolignans veraguensin 1, grandisin 2, and machilin G 3 were tested against Leishmania (Leishmania) amazonensis intracellular amastigotes. Triazole compounds 4-19 were synthetized via Click Chemistry strategy by 1,3-dipolar cycloaddition between terminal acetylenes and aryl azides containing methoxy and methylenedioxy groups as substituents. Our results suggest that most derivatives were active against intracellular amastigotes, with IC 50 values ranging from 4.4 to 32.7 µM. The index of molecular hydrophobicity (ClogP) ranged from 2.8 to 3.4, reflecting a lipophilicity/hydrosolubility rate suitable for transport across membranes, which may have resulted in the potent antileishmanial activity observed. Regarding structure-activity relationship (SAR), compounds 14 and 19, containing a trimethoxy group, were the most active (IC 50 values of 5.6 and 4.4 µM, respectively), with low cytotoxicity on mammalian cells (SI = 14.1 and 10.6). These compounds induced nitric oxide production by the host macrophage cells, which could be suggested as the mechanism involved in the intracellular killing of parasites. These results would be useful for the planning of new derivatives with higher antileishmanial activities.

No abstract

This study compared the Municipal Essential Medicines Lists (REMUME)

This multicenter study aimed to investigate prescribing patterns of drugs at different levels of health care delivery in university-affiliated outpatient clinics located in eight cities in the South and Midwest of Brazil. All prescriptions collected were analyzed for various items, including WHO prescribing indicators. A total of 2,411 prescriptions were analyzed, and 469 drugs were identified. The number of drugs prescribed per encounter, the frequency of polypharmacy, and the percentage of encounters with at least one injection or antibiotic prescribed were higher in centers providing primary health care services, compared to those where this type of care is not provided. Most drugs (86.1%) were prescribed by generic name. In centers with primary health care services, drug availability was higher, drugs included in the National and Municipal Lists of Essential Medicines were more frequently prescribed, and patients were given more instructions. However, warnings and non-pharmacological measures were less frequently recommended. This study reveals trends in drug prescribing at different levels of health care delivery in university-affiliated outpatient clinics and indicates possible areas for improvement in prescribing practices.Keywords: Medicines/rational use. Medicines/prescription. Health Care/quality indicators. Pharmacy/ community services.Este estudo multicêntrico teve como objetivo investigar o padrão de prescrição de medicamentos para pacientes ambulatoriais atendidos em serviços de saúde vinculados a universidades com diferentes níveis de atenção, em oito cidades do sul e centro-oeste do Brasil. As prescrições coletadas foram submetidas à análise de diversos itens, incluindo os indicadores de prescrição propostos pela OMS. No total, 2.411 prescrições foram analisadas e 469 medicamentos foram identificados. O número de medicamentos prescritos por consulta, a frequência de polifarmácia e a porcentagem de consultas com pelo menos um medicamento injetável ou um antimicrobiano prescrito foram maiores em centros de saúde que ofereciam cuidados de atenção básica, em comparação com aqueles que não dispunham desse tipo de atendimento. A maioria dos medicamentos foi prescrita pelo nome genérico (86,1%). Em unidades com cuidados de atenção básica, a acessibilidade foi maior, a prescrição de medicamentos presentes nas Listas Nacional e Municipais de Medicamentos Essenciais foi mais frequente e instruções foram fornecidas aos pacientes mais comumente. Entretanto, advertências e medidas não farmacológicas foram indicadas com menor frequência. Este estudo revela tendências de prescrição de medicamentos em serviços de