Chemical profiles of extracts of four species from Laurencia complex (Ceramiales, Rhodophyta) from different populations collected along Southeast Brazilian coast were assessed by High Performance Liquid Chromatography coupled with a Diode Array Detector in order to observe geographic chemical variability. Aiming to evaluate the impact of chemical diversity on potential pharmaceutical uses, the extracts were tested against the promastigote form of Leishmania amazonensis. The most active extracts were submitted to anti-amastigote and cytotoxicity assays. Principal Component Analysis of the chromatograms resulted in four major groups of chemical profiles according to the presence of leishmanicidal chamigranes (-)-elatol and obtusol. The existence of chemotypes, displaying variable pharmacological action, is proposed for the differences observed in L. dendroidea samples. Although all extracts were found active against promastigote form of L. amazonensis, their efficacy was remarkably different and not related to the variation of (-)-elatol and obtusol, which indicates the presence of additional compounds with antileishmanial activity. Moreover, the active extracts also displayed anti-amastigote activity and none of them were considered cytotoxic. The results highlight that the knowledge of chemical geographic variability can be valuable in the search of new antileishmanial compounds from marine sources.

trans-Desidrocrotonina (t-DCTN), um bioditerpeno do tipo 19-nor-clerodano isolado de Croton cajucara Benth, representa um dos clerodanos da atualidade com maiores índices de investigações científicas. Neste trabalho, uma nova abordagem unindo dados de difração de raios X, dados de ressonância magnética nuclear (NMR) e dados teóricos foi aplicada para a completa caracterização da t-DCTN. Para tanto, a geometria de t-DCTN foi reavaliada por difração de raios X e NMR de ¹H e 13C e foi comparada com os dados teóricos obtidos por B3LYP/6-311G++(d,p). A subsequente avaliação dos valores teóricos e experimentais de deslocamentos químicos de NMR e constantes de acoplamento spin-spin apresentou correlações muito boas entre propriedades magnéticas teóricas e experimentais. Adicionalmente, os índices de deslocalização entre átomos de hidrogênio, d(H,H'), correlacionaram bem com os dados experimentais e calculados de constante de acoplamento. Uma análise topológica complementar utilizando a teoria quântica de átomos em moléculas (QTAIM) mostrou interações intramoleculares para t-DCTN.

trans-Dehydrocrotonin (t-DCTN) a bioactive 19-nor-diterpenoid clerodane type isolated from Croton cajucara Benth, is one of the most investigated clerodane in the current literature. In this work, a new approach joining X-ray diffraction data, nuclear magnetic resonance (NMR) data and theoretical calculations was applied to the thorough characterization of t-DCTN. For that, the geometry of t-DCTN was reevaluated by X-ray diffraction as well as ¹H and 13C NMR data, whose geometrical parameters where compared to those obtained from B3LYP/6-311G++(d,p) level of theory. From the evaluation of both calculated and experimental values of ¹H and 13C NMR chemical shifts and spin-spin coupling constants, it was found very good correlations between theoretical and experimental magnetic properties of t-DCTN. Additionally, the delocalization indexes between hydrogen atoms correlated accurately with theoretical and experimental spin-spin coupling constants. An additional topological analysis from quantum theory of atoms in molecules (QTAIM) showed intramolecular interactions for t-DCTN.

Organic extracts of 36 species of marine algae (sixteen species of Rhodophyta, eight species of Ochrophyta and twelve species of Chlorophyta) from seven locations on the Brazilian coast were evaluated for their anti-HSV-1 and anti-HSV-2 activity resistant to Acyclovir (ACV). Activity tests in crude extracts, followed by the identification of the major compounds present, were performed for all species. The chemical profiles of all crude extracts were obtained by ¹H-NMR and 13C-NMR spectroscopy. The percentage of extracts with antiviral activity was higher for HSV-1 (86.1%) than for HSV-2 (55.5%). The green algae Ulva fasciata and Codium decorticatum both showed the highest activity (99.9%) against HSV-1, with triacylglycerols and fatty acids as the major components. The red alga Laurencia dendroidea showed good activity against HSV-1 (97.5%) and the halogenated sesquiterpenes obtusol and (-)-elatol were identified as the major components in the extract. Against HSV-2, the green alga Penicillus capitatus (Chlorophyta) and Stypopodium zonale (Ochrophyta) were the most active (96.0 and 95.8%). Atomaric acid, a meroditerpene, was identified as the major secondary metabolite in the S. zonale extract. These results reinforce the role of seaweeds as important sources of compounds with the potential to enter into the pipeline for development of new drugs against herpes simplex.

As algas vermelhas do gênero Laurencia são conhecidas como uma riquíssima fonte de metabólitos secundários. As principais classes químicas já isoladas são terpenos - sesquiterpenos, diterpenos, triterpenos - e acetogeninas. Estudos apontam que estas substâncias apresentam importantes atividades biológicas, principalmente citotóxica e antibacteriana. Existem ainda alguns poucos trabalhos com informações sobre atividade antiparasitária, antiviral e antifúngica dos metabólitos de Laurencia. O forte perfil bioativo observado em alguns estudos sugere que alguns destes metabólitos podem ser futuramente utilizados como fármacos ou como protótipos de novos agentes antitumorais e antibacterianos. Muitos dos metabólitos de Laurencia ainda não foram avaliados sob o ponto de vista farmacológico, o que representa um grande potencial a ser explorado por diversos campos da farmacologia.

The red alga of the genus Laurencia is known as an endless source of metabolites. The main substances produced are sesquiterpenes, diterpenes, triterpenes and acetogenins. Many studies reveal that these metabolites are active, especially cytotoxic and antibacterial. There are few other studies that describe the antiparasital, antifungal and antiviral actions of the metabolites produced by the alga of the genus Laurencia. The results observed in some studies suggest that these metabolites may be used in the future as drugs or lead compounds as antitumoral and/or antibacterial agents. Many metabolites have not been submitted to pharmacological studies which still represents an area to be explored.

Foram sintetizados, em um único pote reacional, alguns derivados da α- e β-lapachonas a partir de reação de hetero Diels-Alder, em etanol aquoso, entre estirenos substituídos (como dienófilos) e o-quinonas metídeos (o-QMs) metilênicas e arílicas geradas por condensação de Knoevenagel da 2-hidróxi-1,4-naftoquinona com formaldeído e aldeídos aromáticos.

Methylene and aryl o-quinone methides (o-QMs) generated by Knoevenagel condensation of 2-hydroxy-1,4-naphthoquinone with formaldehyde and arylaldehydes, undergo facile hetero Diels-Alder reaction with some substituted styrenes (as dienophiles) in aqueous ethanol media providing derivatives of α- and β-lapachone.

O diterpeno clerodano trans-desidrocrotonina (1), constituinte majoritário de Croton cajucara, tem sua ocorrência correlacionada com o uso dessa planta na medicina popular. Investigações fitoquímicas levaram ao isolamento dos metabólitos 1, cajucarinolida (6), isocajucarinolida (7), trans-crotonina (2), trans-cajucarina B (3), cis-cajucarina B (4), trans-cajucarina A (5), N-metiltirosina, ácido vanílico e ácido 4-hidróxi-benzóico. 6 e 7 foram sintetizados em bons rendimentos através da oxidação de 1 com oxigênio-singlete. Todos os clerodanos foram ensaiados frente a células da leucemia humana K562 e do carcinoma de Ehrlich. Os efeitos inibitórios do crescimento celular foram dependentes da dose para os ensaios com o carcinoma de Ehrlich com IC50 = 166 µM (1), 164 µM (2), 65 µM (6) e 10 µM (7). Além disso, atividade citotóxica moderada foi observada contra as células da leucemia K562 com IC50 = 38 µM (3), 33 µM (5), 36 µM (6) e 43 µM (7). Os 6 e 7 semi-sintéticos mostraram resultados semelhantes quando comparados com os correspondentes clerodanos naturais.

The clerodane-type diterpene, trans-dehydrocrotonin (1) the major component of Croton cajucara has shown striking correlation with its therapeutic use in traditional folk medicine. Phytochemical investigations led to the isolation of the metabolites 1, cajucarinolide (6), isocajucarinolide (7), trans-crotonin (2), trans-cajucarin B (3), cis-cajucarin B (4), trans-cajucarin A (5), N-methyltyrosine, vanillic acid and 4-hydroxy-benzoic acid. 6 and 7 were synthesized in good yield by regiospecific oxidation of 1 using singlet-oxygen. All clerodanes were studied for their cytotoxic effects against human K562 leukemia and Ehrlich carcinoma cells. Ehrlich carcinoma assays with IC50 = 166 µM (1), 164 µM (2), 65 µM (6) and 10 µM (7) related to cell growth inhibitory effects were dose dependent. Furthermore, moderate cytotoxic activity against K562 leukemia cells was observed with IC50 = 38 µM (3), 33 µM (5), 36 µM (6) and 43 µM (7). The semi-synthetic 2, 6 and 7 showed similar results when compared to the corresponding natural clerodanes.

Os rizomas de Mariscus pedunculatus, quando submetidos à hidrodestilação, forneceram uma mistura do diidrobenzofurano remirol e do benzopirano iso-evodionol, na proporção de 5.7:1. Estas substâncias foram separadas e purificadas por intermédio de sucessivas cromatografias de camada delgada preparativa. As estruturas foram confirmadas por métodos espectroscópicos, incluindo técnicas bidimensionais de RMN, e pelo produto de hidrogenação, no caso do remirol. Entre as substâncias voláteis, foram identificados traços de outros oito sesquiterpenos por CG-EM associada aos cálculos de índice de retenção. O hidrodestilado bruto, assim como as substâncias purificadas foram testadas quanto à atividade antiinflamatória, no modelo de pleurisia induzida em camundongos por lipopolissacarídeo (LPS, 12,5 ng/cavidade). Tanto o extrato bruto quanto o remirol puro (100 e 200 mg kg-1, via oral) demonstraram uma capacidade dose-dependente de inibir o acúmulo de neutrófilos e eosinófilos na cavidade pleural dos animais. O iso-evodionol não apresentou efeito antiinflamatório.

A mixture of the benzofuran remirol and the benzopyran isoevodionol (5.7:1) was extracted by hydrodistillation from rhizomes of Mariscus pedunculatus. They were purified by successive thin layer chromatography. Their structure elucidation were confirmed by 2D-NMR experiments. The structure of remirol was also confirmed by its hydrogenation product. Crude distillate and the pure compounds were screened for anti-inflammatory activity by the use of the mouse pleurisy model induced by lipopolysaccharide (LPS, 12.5 ng/cavity). Both the mixture and remirol showed a dose-dependent (100 and 200 mg kg-1 p. o.) capacity to inhibit neutrophil and eosinophil accumulation in the mouse pleural cavity. In contrast, no anti-inflammatory effect was observed for iso-evodionol.

A view of the general aspects involving the 2D NMR spectroscopy using inverse detection and field gradient techniques is presented through the analysis of a sesquiterpene.