Sixteen 1,4-diaryl-1,2,3-triazole compounds derived from the natural products veraguensin, grandisin and machilin G were synthesized, with yields of 78-92%. Biological activity tests against Leishmania amazonensis promastigotes showed that three of these compounds were the most active, with maximum inhibitory concentration (IC 50 ) values of 1.1, 3.71 and 7.23 µM. One compound was highly active against Leishmania infantum, with an IC 50 value of 5.2 µM, and one derivative showed an IC 50 value of 28.6 µM against Trypanosoma cruzi trypomastigotes. Regarding structureactivity relationship (SAR), hybrid 1,2,3-triazolic compounds containing a methylenedioxy group, showed the best antileishmanial and antitrypanosomal activities.
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.
Context: New antileishmanias are needed because of toxicity, high cost and resistance problems associated with available drugs. Nectandra (Lauraceae) produces several classes of compounds but its essential oil has not previously been reported to have antileishmania activity.Objective: We evaluated the cytotoxicity and antileishmania activity of essential oils from Nectandra amazonum Nees, N. gardneri Meisn., N. hihua (Ruiz & Pav.) Rohwer and N. megapotamica (Spreng.) Mez.Materials and methods:Nectandra oils were extracted from stem bark/leaves by hydrodistillation and compounds were identified by GC-MS. Oils were tested against Leishmania infantum and L. amazonensis intracellular amastigotes and nitric oxide production was evaluated. Cytotoxicity was achieved on NIH/3T3 and J774.A1 cells for the selectivity index (SI).Results and discussion:Nectandra gardneri was active against L. infantum and L. amazonensis (IC50 = 2.7 ± 1.3/2.1 ± 1.06 μg/mL) and contained 85.4% sesquiterpenes, of which 58.2% was intermediol. Besides low cytotoxicity (SI >11.3), N. gardneri induced a significant increase in NO production by L. infantum-infected macrophages. Nectandra hihua had the best activity on L. infantum amastigotes (IC50 = 0.2 ± 1.1 μg/mL). This oil was 89.0% sesquiterpenes, with 28.1% bicyclogermacrene. The two specimens of N. megapotamica had different activities on amastigotes. The one richer in sesquiterpenes (49.9%) was active against both species (IC50 = 12.5 ± 1.4/21.3 ± 1.2) and had phenylpropanoid E-asarone as the main compound (42.4%). Nectandra amazonum showed moderate activity on both the species (IC50 = 31.9 ± 2.0/22.1 ± 1.3 μg/mL) and low selectivity (0.9 < SI >2.6), probably due to the major presence of β-caryophyllene (28.5%).Conclusions: Our data identify compounds that can now be isolated and used for the development of new antileishmanias.
Objetivo: Classificar a adesão dos pacientes ambulatoriais que convivem com vírus da imunodeficiência humana (HIV), bem como descrever os dados socioeconômicos e os fatores que interferem ou não na farmacoterapia. Metodologia: Estudo quantitativo, descritivo e de delineamento transversal realizado a partir da aplicação do instrumento adaptado de Delgado e Lima (2001) para classificação de adesão e para coleta de dados pessoais e investigação de fatores associados a adesão utilizou-se formulários adaptados de Reis (2014). A pesquisa foi constituída por pacientes ambulatoriais que fazem uso de antirretrovirais no serviço de atendimento especializado (SAE) do Hospital Universitário João de Barros Barreto (HUJBB) em Belém do Pará. Resultados/discussão: Os resultados mostraram que a regularidade nas consultas está intimamente ligada com a adesão, que por sua vez está diretamente relacionada a carga viral dos pacientes. Fatores sociais como escolaridade e renda também são aspectos importantes na opção pela adesão ao TARV. Conclusão: A maioria dos pacientes entrevistados são aderentes ao tratamento farmacológico. Por outro lado, pacientes jovens de baixa escolaridade, casados e residentes em área urbana com menor tempo de diagnóstico mostraram-se mais propensos a não aderir ao TARV, indicando uma necessidade de maior atenção pela equipe de saúde.
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