In this paper we continue our efforts in the search for new Schiff bases as resveratrol analogues as promising antitubercular and antileishmanial agents. Compounds were evaluated in vitro against Mycobacterium tuberculosis and Leishmania species. Compounds showed varying activity against promastigotes of all Leishmania species tested (concentration leading to reduction of 50% of parasite growth-IC50 values ranging from 1.60 to 15.53 µg mL-1). Majority of compounds exhibited good results against Leishmania species with IC50 values below 10.00 µg mL-1, with no cytotoxicity against macrophages. One of the analogues showed the best activity against amastigotes of L. amazonensis (IC50 = 5.73 µg mL-1). Furthermore, the compounds showed comparable or better effect than drugs commonly used in tuberculosis treatment such as Cycloserine®. The analogue that was the most active for M. tuberculosis had minimal inhibitory concentration MIC90 = 0.78 µg mL-1. The in vitro cytotoxicity on Vero cells (CC50), as well as the selectivity index (SI = CC50/MIC) were also evaluated, and showed that the synthesized analogues are not cytotoxic.

As leishmanioses são um complexo de doenças causadas por protozoários Leishmania, cujo tratamento é restrito a um número limitado de fármacos que apresentam toxicidade elevada, efeitos colaterais e geralmente custos elevados. Existe uma enorme variedade de plantas tropicais distribuídas no Brasil e para muitas pessoas pobres a terapia para várias doenças baseia-se principalmente no uso de remédios tradicionais obtidos de plantas. Neste trabalho, a atividade citotóxica de 17 extratos metanólicos de plantas foi avaliada em várias espécies de Leishmania e em macrófagos murinos. Dentre eles, os extratos de Casearia sylvestris, Piptocarpha macropoda, Trembleya parviflora, Samanea Tubulosa e Plectranthus neochilus mostraram atividade leishmanicida promissora, exibindo valores de CI50 abaixo de 20 µg/mL em pelo menos uma das espécies de Leishmania. Casearia sylvestris apresentou a atividade mais expressiva em todas as formas promastigotas de espécies de Leishmania (valores de CI50 de 5,4 µg/mL, 5,0 µg/mL, 8,5 µg/mL and 7,7 µg/mL em L. amazonensis, L. braziliensis, L. chagasi e L. major, respectivamente), sendo mais eficaz que o fármaco de referência miltefosina. Apesar do efeito citotóxico em macrófagos (valor de CC50 de 5,2 µg/mL), C. sylvestris exibiu uma forte inibição em formas amastigotas de L. braziliensis (valor de CI50 de 1,3 µg/mL). Mais estudos, incluindo fracionamento bio-guiado, serão realizados para identificar os compostos ativos.

Leishmaniasis is a complex of diseases caused by Leishmania protozoa which treatment is restricted to a limited number of drugs that exhibit high toxicity, collateral effects and are often costly. There are a variety of tropical plants distributed in Brazil, and for many poor people the therapy for several diseases is based mainly on the use of traditional herbal remedies. In this work, the cytotoxic activity of 17 plant methanol extracts was evaluated on several Leishmania species and murine macrophages. Among them, the extract of Casearia sylvestris, Piptocarpha macropoda, Trembleya parviflora, Samanea tubulosa and Plectranthus neochilus showed a promissing leishmanicidal activity, exhibiting IC50 values below of 20 µg/mL against at least one species of Leishmania. Casearia sylvestris showed the most expressive activity against all promastigote forms of Leishmania species (IC50 values of 5.4 µg/mL, 5.0 µg/mL, 8.5 µg/mL and 7.7 µg/mL for L. amazonensis, L. braziliensis, L. chagasi and L. major, respectively), being more effective than the reference drug miltefosine. In spite of the cytotoxic effect on macrophages (CC50 value of 5.2 µg/mL), C. sylvestris exhibited a strong inhibition against intracellular amastigotes of L. braziliensis (IC50 value of 1.3 µg/mL). Further studies, including bio-guided fractionation will be conducted to identify the active compounds.

Em nosso trabalho anterior (Fabri et al. 2009), mostramos que diferentes extratos de Mitracarpus frigidus apresentaram atividades antibacteriana, antifúngica e leishmanicida significativas. Com o objetivo de aprofundar o conhecimento sobre essa espécie, esse trabalho objetiva identificar os constituintes químicos e avaliar as atividades biológicas in vitro de seu óleo essencial. Dessa forma, o óleo essencial das partes aéreas de M.frigidus foi obtido por hidrodestilação e analisado por CG/EM. Entre os compostos detectados, 11 foram identificados, sendo linalol e o acetato de eugenol os componentes majoritários. O óleo essencial de M. frigidus exibiu moderada atividade antibacteriana contra Staphyloccocus aureus, Bacillus cereus, Pseudomonas aeruginosa e Enterobacter cloacae (CIM 250 µg/mL). Por outro lado, apresentou forte efeito antifúngico contra Cryptoccocus neoformans (CIM 8 µg/mL) e Candida albicans (CIM 63 µg/mL). Expressiva atividade contra as formas promastigostas de Leishmania major e Leishmania amazonensis com valores CI50 de 47, 2 e 89, 7 µg/mL, respectivamente, também foi observada. Além disso, a atividade antioxidante foi investigada através do ensaio com o radical DPPH e este apresentou uma significativa atividade com CI50 de 38 µg/mL. A citotoxidade contra Artemia salina foi moderada com CL50 de 88 µg/mL. Os resultados aqui apresentados são o primeiro relato sobre a composição química e propriedades biológicas do óleo essencial M. frigidus.

In our previous work (Fabri et al. 2009), we showed that different extracts of Mitracarpus frigidus had significant antibacterial, antifungal and leishmanicidal activities. In order to increase our knowledge about this species, this work assesses the chemical composition and the in vitro biological activity of its essential oil. Thus, the essential oil obtained by hydrodistillation of the aerial parts of M. frigidus was analyzed by GC/MS. Among several compounds detected, 11 were identified, being linalool and eugenol acetate the major components. The essential oil exhibited a moderate antibacterial effect against Staphyloccocus aureus, Bacillus cereus, Pseudomonas aeruginosa and Enterobacter cloacae (MIC 250 µg/mL). On the other hand, it showed a strong antifungal effect against Cryptoccocus neoformans (MIC 8 µg/mL) and Candida albicans (MIC 63 µg/mL). Expressive activity against L. major and L. amazonensis promastigote forms with IC50 values of 47.2 and 89.7 µg/mL, respectively, were also observed. In addition, the antioxidant activity was investigated through DPPH radical-scavenging and showed a significative activity with IC50 of 38 µg/mL. The cytotoxicity against Artemia salina was moderate with LC50 of 88 µg/mL. The results presented here are the first report on the chemical composition and biological properties of M. frigidus essential oil.

O fracionamento biomonitorado do extrato diclorometânico de Mitracarpus frigidus forneceu a piranonaftoquinona psicorubrina. Essa substância, até então desconhecida no gênero Mitracarpus, teve sua atividade biológica avaliada contra várias bactérias e dois fungos, três linhagens de células tumorais (HL60, Jurkat e MCF-7) e quatro espécies de Leishmania. Sua estrutura foi confirmada por meio de ¹H, 13C, ¹H-COSY, IR e UV-Vis e espectrometria de massas. Psicorubrina exibiu uma atividade antitumoral promissora com CI50 de 4,5, 5,6 e 1,1 µM para HL60, Jurkat e MCF-7, respectivamente. Atividade antimicrobiana, principalmente contra Cryptococcus neoformans (CIM de 87,3 µM), foi observada. Um pronunciado potencial leishmanicida também foi verificado com CI50 variando de 1,7 - 2,7 µM para as diferentes espécies de Leishmania testadas. Este é o primeiro relato da presença de piranonaftoquinonas no gênero Mitracarpus, que poderão ser úteis como marcadores quimiotaxonômicos.

The bioactivity guided fractionation of the dichloromethane extract of Mitracarpus frigidus afforded the pyranonaphthoquinone psychorubrin. This compound, hitherto unknown in the genus Mitracarpus, had its biological activity evaluated against one panel of bacteria and two fungi, three tumor cell lines (HL60, Jurkat and MCF-7) and four Leishmania species. Its identity was confirmed unambiguously by ¹H, 13C, ¹H-COSY, IR and UV-Vis spectroscopy and mass spectrometry. Psychorubrin displayed a very promising antitumor with IC50 of 4.5, 5.6 and 1.1 µM for HL60, Jurkat and MCF-7 cell lines, respectively. Antimicrobial activity, mainly against Cryptococcus neoformans (MIC of 87.3 µM) was observed. A pronounced antileishmanial potential was also verified with IC50 varying from 1.7 to 2.7 µM for the Leishmania species tested. This is the first report of the presence of pyranonapthoquinones in the Mitracarpus genus, which may serve as a chemotaxonomical marker.

Leishmaniasis is an infection of viscera or tegument caused by protozoa Leishmania sp. The extensive period required for the treatment, which involves the use of toxic medicines, leads patients to drop treatment increasing the development of resistant forms of Leishmania sp. Lantana camara L., Verbenaceae, is a tropical plant native from America. Folk uses have been described for treatment of tumors, tetanus, rheumatism and malaria. This study evaluates the leishmanicidal activity of the essential oil of leaves from L. camara on promastigote forms of Leishmania chagasi and L. amazonensis and its toxic effects on Artemia salina (brine shrimp test), macrophage cultures and BALB/c mice. The chemical composition was evaluated using the gas chromatography coupled with mass spectrometer (GC-MS). Thirty substances, mostly mono and sesquiterpenes were identified. The most representative constituents were: germacrene D (24.90%), farnesene derivatives (22%) and (E)-cariophylene (14.31%). Bioassays revealed a significant leishmanicidal activity of essential oil against L. amazonensis (IC50 0.25 µg/ mL) and a potential toxic effect on Brine shrimp (LC50 10 µg/mL) and macrophage assays (CC50 4 µg/mL), while there was no toxic manifestation on mice. The data show the relevant potential of L. camara as a source of medicine for leishmaniasis treatment.

O presente trabalho investigou as atividades antimicrobiana e leishmanicida das sementes de Pterodon emarginatus Vogel. O potencial antimicrobiano do óleo essencial (OE) obtido das sementes foi avaliado através dos testes de difusão em ágar (10, 25 e 50 mg) e determinação da concentração inibitória mínima e utilizou os microorganismos-padrão: Staphylococcus aureus ATCC 25923, Streptococcus mutans ATCC 25175, Pseudomonas aeruginosa ATCC 90271, Escherichia coli ATCC 10530 e Candida albicans ATCC 10231. A atividade leishmanicida do OE e frações (6,25 - 100 µg/mL) obtidas das sementes de P. emarginatus foram testadas, in vitro, sobre formas promastigotas de L. amazonensis e L. chagasi. O OE das sementes de P. emarginatus inibiu o crescimento somente de S. aureus (CIM = 2,5 mg/mL). As frações hexânica (IC50 = 50,06 µg/mL) e butanólica (IC50 = 46,65 µg/mL) apresentaram atividade frente às formas promastigotas de L. amazonensis, porém não apresentaram atividade frente a L. chagasi. Os resultados indicam que as moléculas bioativas presentes nas sementes de P. emarginatus podem ser utilizadas como protótipos para o desenvolvimento de fármacos e/ou como fonte de matérias-primas farmacêuticas.

The present work investigated the antimicrobial and leishmanicidal activities of seeds of Pterodon emarginatus. The tests of diffusion in agar (10, 25 and 50 mg) and determination of minimum inhibitory concentration (MIC) were performed using essential oil (EO) obtained from seeds using the standard microorganisms: Staphylococcus aureus ATCC 25923, Streptococcus mutans ATCC 25175, Pseudomonas aeruginosa ATCC 90271, Escherichia coli ATCC 10530 and Candida albicans ATCC 10231. Leishmanicidal activity of the EO and fractions (6.25 - 100 µg/ml) obtained of seeds of P. emarginatus was evaluated in vitro using L. amazonensis and L. chagasi promastigote forms. The EO inhibited the growth of S. aureus (MIC = 2.5 mg/ml). The hexane (IC50 = 50.06 µg/ ml) and butanol (IC50 = 46.65 µg/ml) fractions showed activity against L. amazonensis promastigote forms, but did not against L. chagasi promastigote forms. The results indicate that the bioactive molecules present in the seeds of P. emarginatus can be used as prototype for the development of drug and/or as source pharmaceutical material.