Recebido em 24/8/04; aceito em 17/2/05; publicado na web em 11/7/05 CHEMICAL CONSTITUENTS OF Luehea divaricata Mart. (TILIACEAE). Chemical studies of the leaves of L. divaricata afforded 3β-p-hydroxybenzoyl-tormentic acid, a triterpene with an ursene-type skeleton, a mixture whose main compound was an oleanene derivative, the maslinic acid, a C-glycoside flavone, vitexin and glucopyranosylsitosterol. A flavonoid, characterized as (-)-epicatechin, which belongs to the flavan-3-ol class, was isolated from the stem's bark. The structures of the compounds were elucidated by spectroscopic analysis. The antibacterial, antifungal and antiproliferative activities of the crude methanolic extracts of leaves and bark were evaluated and the antibacterial properties of the fractions of the barks were also investigated.Keywords: Luehea divaricata; triterpenes; flavonoids. INTRODUÇÃOO sul da África e o Brasil constituem os dois principais centros de dispersão da família Tiliaceae, a qual conta com 35 gêneros e 370 espécies das quais cerca de 55 a 60 espécies, distribuídas em 13 gêneros, ocorrem no Brasil 1 . Luehea divaricata Mart. (Tiliaceae), uma árvore de grande porte (15 a 25 m), popularmente conhecida como açoita-cavalo, açoita-cavalo miúdo, ibatingui, ivatingui, paude-canga e caiboti, também apresenta as sinonímias de Luehea speciosa Wild., Brotera mediterranea Vell. e Luehea parvifolia Mart. e é encontrada nos estados brasileiros da Bahia, Rio de Janeiro, São Paulo, Minas Gerais, Goiás e do Mato Grosso do Sul até o Rio Grande do Sul 2 . As folhas de Luehea são comercializadas como fitoterápicos contra disenteria, leucorréia, reumatismo, blenorragia e tumores; a infusão das flores é usada contra bronquite e a raiz é depurativa 3 . Outras atividades biológicas e usos populares para a espécie L. divaricata foram encontradas na literatura 4 , descrevendo o isolamento do triterpeno, inédito à época, o ácido 3β-p-hidroxibenzoil tormêntico (1) e da mistura contendo o ácido maslínico (2). Além deste relato, nenhum outro estudo químico foi encontrado na literatura para qualquer espécie do gênero Luehea.O presente trabalho relata os principais constituintes químicos isolados das cascas do caule e das folhas de L. divaricata, bem como a avaliação das atividades antifúngica, antibacteriana e antiproliferativa dos extratos brutos, e antibacteriana das frações do extrato das cascas do caule. O estudo químico do extrato bruto metanólico das folhas resultou, em um primeiro momento, no isolamento do ácido 3β-p-hidroxibenzoil tormêntico (1), triterpeno com esqueleto básico dos ursenos, e de uma mistura cuja substância majoritária foi o ácido maslínico (2), triterpeno derivado dos oleanenos 4 . Posteriormente, foram isolados do mesmo extrato a vitexina (3), uma flavona C-glicosilada, e o esteróide glicopiranosilsitosterol (4). O flavonóide (-)-epicatequina (5), um flavan-3-ol, foi isolado do extrato bruto metanólico das cascas do caule. As estruturas das substâncias isoladas foram elucidadas com base nas análises dos dados espectrais de I...

Thiosemicarbazides are compounds known for their biological activity, particularly their antimicrobial properties, which include activity against fungi. The difficulty of treating fungal diseases induced us to assess the antifungal properties of some novel thiosemicarbazide compounds. We selected the natural products limonene and camphene as sources for the preparation of these new thiosemicarbazide derivatives. The compound N(4)-[2,2-dimethyl-3-methylnorbornane]-thiosemicarbazide (TIO C) showed an antifungal effect on Trichophyton mentagrophytes, with values of MIC = 55 μmol L-1 and MFC = 110 μmol L-1. Scanning-electron microscopy showed a decrease in mycelium development and morphological alterations of T. mentagrophytes cultured on nail fragments and treated with TIO C. In an attempt to discover its mode of action, we noted that ergosterol is apparently not a target of TIO C activity. An effect of TIO C on T. mentagrophytes cell walls and dividing cross-walls was shown by observed impairment of the fluorescence of tissues stained with calcofluor white, a specific marker for fungal chitin, suggesting that the compound can affect and damage the cell-wall structure or may interfere with its formation, during cell division, growth, and morphogenesis. This approach to the synthesis of new derivatives might provide interesting compounds with greater biological activity in pharmacological research.

Paracoccidioidomycosis (PCM) is a systemic granulomatous human mycosis caused by fungi of the genus Paracoccidioides, which is geographically restricted to Latin America. Inhalation of spores, the infectious particles of the fungus, is a common route of infection. The PCM treatment of choice is azoles such as itraconazole, but sulfonamides and amphotericin B are used in some cases despite their toxicity to mammalian cells. The current availability of treatments highlights the need to identify and characterize novel targets for antifungal treatment of PCM as well as the need to search for new antifungal compounds obtained from natural sources or by chemical synthesis. To this end, we evaluated the antifungal activity of a camphene thiosemicarbazide derivative (TSC-C) compound on Paracoccidioides yeast. To determine the response of Paracoccidioides spp. to TSC-C, we analyzed the transcriptional profile of the fungus after 8 h of contact with the compound. The results demonstrate that Paracoccidioides lutzii induced the expression of genes related to metabolism; cell cycle and DNA processing; biogenesis of cellular components; cell transduction/signal; cell rescue, defense and virulence; cellular transport, transport facilities and transport routes; energy; protein synthesis; protein fate; transcription; and other proteins without classification. Additionally, we observed intensely inhibited genes related to protein synthesis. Analysis by fluorescence microscopy and flow cytometry revealed that the compound induced the production of reactive oxygen species. Using an isolate with down-regulated SOD1 gene expression (SOD1-aRNA), we sought to determine the function of this gene in the defense of Paracoccidioides yeast cells against the compound. Mutant cells were more susceptible to TSC-C, demonstrating the importance of this gene in response to the compound. The results presented herein suggest that TSC-C is a promising candidate for PCM treatment.

No abstract

As folhas de Hyptis ovalifolia Benth. (Lamiaceae) foram submetidas à hidrodestilação e a fração volátil foi investigada por CG/EM. O componente principal, (R)-6-[(Z)-1-heptenila]-5,6-diidro-2H-piranona (1), representando 60% do óleo essencial, foi isolado por cromatografia em coluna e identificado por métodos espectroscópicos. O composto mostrou atividade in vitro contra 4 espécies (60 isolados clínicos) dos dermatófitos: Microsporum canis, Microsporum gypseum, Tricophyton mentagrophytes e Tricophyton rubrum com concentração inibitória mínima variando de 125-7,8 µg mL -1 .The leaves of Hyptis ovalifolia Benth. (Lamiaceae) were subjected to hydrodistillation and the resulting volatiles were investigated by GC/MS. The main constituent representing 60% of the essential oil was isolated by column chromatography and identified by spectroscopic methods as (R)-6-[(Z)-1-heptenyl]-5,6-dihydro-2H-pyran-2-one (1). This compound showed strong in vitro activity against four dermatophyte fungi Microsporum canis, Microsporum gypseum, Tricophyton mentagrophytes, and Tricophyton rubrum (a total of 60 strains) with a minimal inhibitory concentration observed in the range of 125-7.8 µg mL -1 . Keywords:Hyptis ovalifolia, essential oil, antifungal activity, Lamiaceae, (R)-6-[(Z)-1-heptenyl]-5,6-dihydro-2H-pyran-2-one IntroductionThe genus Hyptis Jacq. (Lamiaceae) includes about 400 species that mainly occur in tropical America. 1 This genus represents an important source of bioactive constituents possessing interesting biological effects, such as antimicrobial, cytotoxic and insecticidal activities. [2][3][4] In the course of our program aimed to isolate new antifungal compounds from Brazilian Cerrado plants, the essential oil of Hyptis ovalifolia Benth., popularly known in Brazil as 'malva do cerrado', was found to show a strong activity against dermatophytes. In this paper we report the isolation, structural determination and antifungal activity of the major constituent of this essential oil against Microsporum canis, Microsporum gypseum, Tricophyton mentagrophytes, and Tricophyton rubrum using the agar dilution method 5 to determine the minimal inhibitory concentrations (MICs). Experimental General experimental proceduresThe GC/MS analyses were carried out using a QP5050 GC/MS (Shimadzu), equipped with J&W Scientific DB-5 fused silica capillary column (30 m x 0.25 mm x 0.25 µm). The oven temperature was programmed as follows: 60 °C for 2 min with an increase of 3 °C min -1 to 240 °C, followed by 10 °C min -1 to 280 °C for 2 min. Carrier gas: Helium (1 mL min -1 ). The injector was operated in split mode with ratio 1:50 at 220 °C and interface temperature at 240 °C. The retention index were obtained by co-injecting the oil 757 Chemical Composition and Antifungal Activity of the Essential Oil of Hyptis ovalifolia Benth. Vol. 15, No. 5, 2004 sample with an n-alkanes series 6 and used to identify the compounds present, together with the comparison to the NIST (NIST 21 and NIST 107) mass spectral library. NMR spectra were recorde...