Neolignans isolated from twigs of Nectandra leucantha Ness & Mart (Lauraceae) displayed in vitro antileishmanial activity

Abstract

BackgroundThe therapeutic arsenal for the treatment of Leishmaniasis is limited and includes toxic compounds (antimonials, amphotericin B, pentamidine and miltefosine). Given these aspects, the search for new compounds based on floristic biodiversity is crucial. In the present work, we report the isolation, characterization and antileishmanial activity of six related neolignans (1–6) of bioactive extract from Nectandra leucantha (Lauraceae) twigs.MethodsDried and powdered twigs of N. leucantha were exhaustively extracted using n-hexane. The crude extract was dereplicated by HPLC/HRESIMS and subjected to column chromatography to yield pure compounds 1–6. Their chemical structures were identified via NMR and comparison of obtained data with those previously published in the literature. Biological assays of compounds 1–6 and their respective monomers (eugenol and methyleugenol) were performed using promastigote and amastigote forms of Leishmania (L.) infantum.ResultsDereplication procedures followed by chemical characterization of isolated compounds by NMR enabled the identification of related neolignans 1–6. Neolignans 2, 4 and 6 showed potential against amastigote forms of L. (L.) infantum (EC50 values of 57.9, 67.7 and 13.7 μM, respectively), while compounds 1 and 3 were inactive. As neolignans 2–4 are chemically related, it may be suggested that the presence of the methoxyl group at C4 constitutes an important structural aspect to increase antileishmanial potential against amastigote forms. Compound 6, which consists of a methylated derivative of compound 5 (inactive) showed antileishmanial activity similar to that of the standard drug miltefosine (EC50 = 16.9 μM) but with reduced toxicity (SI = 14.6 and 7.2, respectively). Finally, two related monomers, eugenol and methyleugenol, were also tested and did not display activity, suggesting that the formation of dimeric compounds by oxidative coupling is crucial for antiparasitic activity of dimeric compounds 2, 4 and 6.ConclusionThis study highlights compound 6 against L. (L.) infantum amastigotes as a scaffold for future design of new compounds for drug treatment of visceral leishmaniasis.

Discovery of New Hits as Antitrypanosomal Agents by In Silico and In Vitro Assays Using Neolignan-Inspired Natural Products from Nectandra leucantha

“…Fresh flowers of Nectandra leucantha (Lauraceae) were collected in Cubatão city (São Paulo state, Brazil), in March 2019, from a previously investigated specimen [ 11 ]. After air-drying, N. leucantha flowers (55 g) were powdered and exhaustively extracted with n -hexane (10 × 250 mL).…”

“…Considering the urgent need for new treatments, natural products can be considered important sources to design potent and safer drug candidates [ 4 , 5 , 6 , 7 ]. Different studies [ 8 , 9 , 10 ] have shown that neolignans isolated from leaves and twigs of Nectandra leucantha (Lauraceae), as well as several related semi-synthetic derivatives, exhibited in vitro activity against T. cruzi [ 1 , 8 , 11 ]. In this work, molecular modeling techniques were employed to aid in the design of new neolignan-based compounds with improved biological activity against T. cruzi .…”

Avaliação Do Consumo Alimentar E Peso Corporal Em Camundongos Swiss Machos Tratados Com Extrato Metanólico De Planta Medicinal

“…O potencial leishmanicida do extrato de n-hexano de galhos de N. leucantha foram avaliados contra a promastigota e formas amastigotas de L. (L.) infantum e na concentração de 300 μg/mL houve morte de 100% dos parasitos (GRECCO et al, 2018 ativa-livre e ativa resistida de leve intensidade em membros inferiores, sendo este último com auxílio de faixa elástica. Ao final dos exercícios foi realizada massoterapia para eliminação de pontos gatilhos ao redor da escápula para alívio da dor (Rodrigues et al, 2016).…”

Os Efeitos Da Microcorrente E Do Oligoelemento Selênio Nas Disfunções Teciduais Da Face Do Tabagista

“…O potencial leishmanicida do extrato de n-hexano de galhos de N. leucantha foram avaliados contra a promastigota e formas amastigotas de L. (L.) infantum e na concentração de 300 μg/mL houve morte de 100% dos parasitos (GRECCO et al, 2018 A evolução do tratamento de sensibilidade tátil foi observada através da avaliação feita pela terapeuta com auxilio do mapa de dermátomos e recursos de diagnóstico clínico, como agulha e pinça do martelo neurológico de aço inox da marca Buck. A função da marcha foi avaliada por avaliação da força, de acordo com a Escala Kendall e inspeção do paciente durante a atividade de deambulação, com registro na ficha de evolução de padrões pré e pós-terapêuticos.…”