Marine cyanobacteria (blue-green algae) have been shown to possess an enormous capacity to produce structurally diverse natural products that exhibit a broad spectrum of potent biological activities, including cytotoxic, antifungal, antiparasitic, antiviral and antibacterial activities. Using mass spectrometry-guided fractionation together with molecular networking, cyanobacterial field collections from American Samoa and Palmyra Atoll yielded three new cyclic peptides, tutuilamides A-C. Their structures were established by spectroscopic techniques including 1D and 2D NMR, HR-MS, and chemical derivatization. Structure elucidation was facilitated by employing advanced NMR techniques including non-uniform sampling in combination with the 1,1-ADEQUATE experiment. These cyclic peptides are characterized by the presence of several unusual residues including 3-amino-6-hydroxy-2-piperidone and 2-amino-2-butenoic acid, together with a novel vinyl chloride-containing residue. Tutuilamides A-C show potent elastase inhibitory activity together with moderate potency in H-460 lung cancer cell cytotoxicity assays. The binding mode to elastase was analyzed by X-ray crystallography revealing a reversible binding mode similar to the natural product lyngbyastatin 7. The presence of an additional hydrogen bond with the amino acid backbone of the flexible side chain of tutuilamide A, compared to lyngbyastatin 7, facilitates its stabilization in the elastase binding pocket and possibly explains its enhanced inhibitory potency.

The objectives of this work were to carry out a comparative chemical study and to evaluate the antinociceptive and anti-inflammatory activities of ethanol extracts (EtOHE) and vanilic acid (VA) from cultivated and wild Amburana cearensis A.C. Smith (Fabaceae), an endangered species used in Northeast Brazil for the treatment of asthma. The HPLC analysis of EtOHE, showed that coumarin (CM) and VA were the major constituents from the cultivated plant, while in the extract from the wild plant the major constituents were amburoside A (AMB) and CM. Pharmacological tests were performed with male Swiss mice or male Wistar rats acutely administered with 100-400mg/kg, p.o. of EtOHEs or 12.5-50mg/kg, p.o. of VA. EtOHEs from A. cearensis with 4, 7 or 9 months of cultivation significantly inhibited, from 32 to 64%, both phases of the formalin test in mice. Similar results were observed with the EtOHE from the wild species. VA significantly reduced both phases of the formalin test. This effect was partially reversed by naloxone. EtOHE from cultivated or wild A. cearensis inhibited the carrageenan (Cg)-induced mice paw edema. Furthermore, VA inhibited the paw edema and the leukocyte migration in rat peritoneal cavity induced by Cg. On the other hand, it did not inhibit the edema and the increase of vascular permeability induced by dextran in the rat paw. All together, these results indicate that the EtOHE from cultivated A. cearensis exhibit similar chemical and pharmacological profiles, as related to the wild plant. VA is, at least partially, responsible for these pharmacological effects. Its antinociceptive effect occurs by a mechanism partly dependent upon the opioid system, while the anti-inflammatory action was manifested in inflammatory processes dependent on polymorphonuclear cells and are probably related to the VA inhibition of cytokines as observed by others.

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Amburana cearensis A. C. Smith, Fagaceae, is a medicinal plant commonly known as 'cumaru' and used in Northeast Brazil for the treatment of respiratory tract diseases. In the present work, we investigated the anti-inflammatory and smooth muscle relaxant activities of the hydroalcoholic extract (HAE), coumarin (Coum) and fl avonoid fraction (FF) isolated from the trunk barks of Amburana cearensis A. C. Smith. It was shown that HAE (200 and 400 mg/kg), Coum (20 and 40 mg/kg) and FF (40 mg/kg), administered orally, significantly inhibited both leukocyte and neutrophil migrations, in the carrageenan or N-formyl-methyl-leucyl-phenylalanine (fMLP)-induced migration in rat peritoneal cavity. The increase in cutaneous vascular permeability induced by serotonin in rats was significantly blocked by HAE (150 mg/kg, i.p.), Coum (5 mg/kg, i.p.) and FF (20 mg/kg, i.p.). However, only HAE blocked the histamine effect on Evans blue extravasation. In the guinea-pig trachea precontracted with carbachol (0.3 microM), histamine (0.1 microM) or KCl (0.1 M), the HAE, Coum and FF evoked a concentration-dependent relaxation in the presence of the three agonists. HAE (100-800 microg/ml) and Coum (4-32 microg/ml) also caused significant relaxation of the rat vas deferens previously contracted with adrenaline, acetylcholine or barium chloride. In addition, HAE, Coum and FF inhibited the histamine and serotonin-induced increase of cutaneous vascular permeability in rats.

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Recebido em 26/10/05; aceito em 30/3/06; publicado na web em 22/8/06 CHEMICAL CONSTITUENTS OF TRUNK BARK OF Amburana cearensis A.C. SMITH. The phytochemical analysis of the ethanol extract trunk bark of Amburana cearensis allowed the isolation and identification of twelve constituents: coumarin, sucrose, two phenol acids (vanillic acid and protocatechuic acid), five flavonoids (afrormosin, isokaempferide, kaempferol, quercetin and 4'-methoxy-fisetin), a phenol glucoside (amburoside A) and a mixture of glucosilated β-sitosterol and stigmasterol. Their structures were elucidated by spectroscopic methods such as IR, MS, 1 H and 13 C NMR, including uni and bidimensional techniques, in addition to comparison with literature data.Keywords: Amburana cearensis; chemical constitution; spectroscopic data. INTRODUÇÃOAmburana cearensis A.C. Smith (sin. Torresea cearensis Fr. All) pertence à família Leguminoseae Papilionoideae (Fabaceae), sendo ao lado da A. acreana os únicos representantes do gênero. Popularmente, é conhecida por diversas designações, como imburanade-cheiro, cerejeira e cumaru. Esta última denominação, a mais famosa delas, freqüentemente provoca confusões com outra leguminosa homônima chamada Dipteryx odorata, ambas ricas em cumarina (1). Já o termo imburana costuma provocar iguais equívocos na identificação, por se referir também à Commiphora leptophloeos (Burseraceae), conhecida comumente como imburana-de-espinho 1 .Embora considerada nativa do sertão nordestino, a ocorrência de A. cearensis pode ser observada em praticamente toda América do Sul (do Peru à Argentina) 2 , apresentando-se como uma árvore frondosa, a qual pode atingir até 15 m de altura, com flores brancas, vagem achatada e casca do caule vermelho-pardacenta cujo agradá-vel odor é conferido pela cumarina. Suas sementes são pretas, aladas e exalam forte cheiro de cumarina (semelhante à baunilha) 3 . No Nordeste, o período de floração ocorre no início da estação seca, entre maio e julho, e a frutificação se dá de agosto a outubro.Sob o ponto de vista econômico, A. cearensis apresenta inestimável importância comercial dadas suas várias aplicações, sendo largamente empregada na carpintaria e perfumaria. Comercializada com o nome de cerejeira-do-nordeste, sua madeira é utilizada na fabricação de móveis, portas, janelas e caixotaria, devido à reconhecida durabilidade. As sementes servem como aromatizantes e repelentes de insetos para roupas e estantes, podendo também ser utilizadas na fabricação de um pó fino, designado rapé-de-imburana, empregado para induzir espirros no tratamento de "estalecido" (congestão nasal por acúmulo de secreção) 1 .Na medicina popular, as cascas do caule são tradicionalmente utilizadas na preparação de "lambedôs" caseiros para tratamento de doenças respiratórias, como gripe, resfriado, bronquite e asma 4 . Industrialmente, a forma farmacêutica disponível é o xarope de cumaru, produzido pelo Programa Farmácias Vivas, Farmácia-Escola/UFC e por algumas empresas privadas. Ensaios farmacológicos pré-clínicos demonstraram ati...

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