ABSTRACT Thirteen natural products derivatives of hydroxyl amide class, three described for the first time, were synthesized by reaction of three indole acids and 3,4,5-trimethoxybenzoic acid with six different amino alcohols in the presence of triphenylphosphine and N-bromosuccinimide. The derivatives were tested against the Gram (+) bacteria Staphylococcus aureus and Bacillus cereus, Gram (-) Pseudomonas aeruginosa and Escherichia coli, besides the yeast Candida albicans. One of the compounds (7) was selectively active against C. albicans (91.3 ± 0.49% inhibition) showing a great potential as a new drug lead, since it was more active than the positive control, miconazole (88.7 ± 2.41% inhibition). Regarding bacterial inhibition, compounds demonstrated mild activity, but inhibition of compounds 9, 10 and 13 towards E. coli is of interest since it is difficult to find drugs selectively active against Gram (-) bacteria. Most of the compounds were very active in the acetylcholinesterase inhibition assay. Compound 7 was again the most active (93.2 ± 4.47%), being more potent than the control galantamine (90.3 ± 0.45%). The most active gallic acid derivatives, compounds 3, 7 and 8 have in common, besides gallic acid skeleton, a (CH2)2OH group, which may be one of the structural requirements for AChE inhibition.

Annona cornifolia A. St. -Hil. é uma pequena árvore anual perene encontrada no cerrado brasileiro; seu fruto verde é usado popularmente no tratamento de úlceras. As acetogeninas isoladas a partir das sementes de Annona cornifolia anteriormente apresentaram atividade antioxidante. Continuando as nossas investigações sobre as atividades biológicas das acetogeninas, quatro misturas binárias e dez acetogeninas bis-tetra-hidrofurânicas adjacentes puras foram avaliadas quanto às atividades: citotóxica (sobre três linhagens de células tumorais humanas), antifúngica (sobre Paracoccidioides brasiliensis), tripanocida (sobre Trypanosoma cruzi) e leishmanicida (sobre Leishmania amazonensis). As acetogeninas apresentaram atividade citotóxica, confirmando seu uso potencial na terapia anticâncer. Quanto às atividades leishmanicida e tripanocida, foi observada uma inibição de 87% das formas amastigotas de L. amazonensis e 100% de formas amastigotas e tripomastigotas de T. cruzi, quando testadas a uma concentração de 20 µg mL–1. Além disso, seis acetogeninas mostraram maior atividade sobre todas as três cepas testadas de P. brasiliensis que o trimetoprim-sulfametoxazol, um medicamento usado no tratamento da paracoccidioidomicose. Assim, as acetogeninas podem ser uma alternativa no tratamento de uma série de doenças que têm um enorme impacto em milhões de pessoas no mundo. Este trabalho relata pela primeira as atividades antifúngica, leishmanicida e tripanocida para estas acetogeninas.

Annona cornifolia A. St. -Hil. is a small annual perennial tree found in the Brazilian savannah; their green fruit is popularly used in the treatment of ulcers. The acetogenins isolated from the seeds of Annona cornifolia previously showed to possess antioxidant activity. In continuation of our investigations on the biological activities of acetogenins, four binary mixtures and ten pure adjacent bis-tetrahydrofuran annonaceous acetogenins were evaluated: the cytotoxic (against three human tumor cell lines), antifungal (against Paracoccidioides brasiliensis), trypanocidal (against Trypanosoma cruzi) and leishmanicidal (against Leishmania amazonensis) activities. Acetogenins presented cytotoxic activity confirming their potential use in anti-cancer therapy. Regarding leishmanicidal and trypanocidal activities, an inhibition of 87% of L. amazonensis amastigotes and 100% of T. cruzi amastigotes and trypomastigotes was observed, when tested at the concentration of 20 µg mL–1. Moreover, six acetogenins showed more activity against all the three tested isolates of P. brasiliensis than trimethoprim-sulfamethoxazole, a drug used for treating paracoccidioidomycosis. Thus, acetogenins may be an alternative in treating a number of diseases that have a huge impact on millions of people worldwide. This paper reports for the first time the antifungal, leishmanicidal and trypanocidal activities for these acetogenins.

Decoction of roots of the Amazonian palm açaí (Euterpe precatoria Mart.) is widely used by Brazilian and Peruvian people as an anti-inflammatory, to heal kidney and liver diseases and against snake bites. In this study, the antioxidant activity of extracts and flavonoids (quercetin, catechin, epicatechin, rutin and astilbin) isolated from roots and leaf stalks of E. precatoria was investigated using β-carotene in TLC plates and DPPH radical scavenging in a spectrophotometric bioassay. All extracts and flavonoids showed activity. Also, the cytotoxic activity of these extracts was evaluated by the brine shrimp (Artemia salina) larvicide bioassay and was lower than that of lapachol, used as control. The presence of flavonoids and sitosterol-3-O-β-D-glucopyranoside in the extracts can justify the use of the plant in traditional medicine.

O uso de microrganismos para a realização de reações químicas tem sido explorado como uma ferramenta moderna em química. Neste trabalho explorou-se a habilidade dos fungos Beauveria bassiana e Aspergillus niger de modificarem quimicamente a estrutura de compostos indólicos, uma classe de substâncias com diversas atividades biológicas relatadas. A 3-indolacetonitrila foi reduzida, com formação do 3-metilindol por Beauveria bassiana, enquanto Aspergillus niger converteu a triptamina em um derivado oxidado, a 5-hidroxiindol-3-acetamida. A oxidação ocorreu somente no experimento sob agitação e provavelmente está relacionada ao alto grau de oxigenação da reação. A ocorrência de redução e oxidação de derivados indólicos ilustra bem a versatilidade do uso de microorganismos para a condução de uma grande variedade de reações químicas de interesse industrial.

Chemical reactions performed by microorganisms have been used as a modern tool in chemistry. In this work, the ability of the fungi Beauveria bassiana and Aspergillus niger to modify the chemical structure of indole compounds was studied. Beauveria bassiana was able to transform 3-indolylacetonitrile into 3-methylindole while Aspergillus niger transformed tryptamine into 5-hydroxyindole-3-acetamide. Interestingly, these fungi were able to perform both reduction and oxidation of the indole compounds fed, the oxidation occurring with improved levels of oxygen uptake. The results prove once more the versatility of microorganisms to perform a wide range of industrially attractive chemical reactions.

O ácido caurenóico, um diterpeno caurânico, mostrou-se ativo in vitro contra formas tripomastigotas do Trypanosoma cruzi. Uma ação lítica sobre os eritrócitos foi uma das limitações encontradas para esta atividade. A síntese de doze derivados deste ácido: quatro amidas, quatro aminas (e três cloridratos) e quatro oximas foi realizada, com o objetivo de se tentar diminuir ou eliminar esse efeito secundário e, se possível, aumentar a atividade em relação ao material de partida. Dentre esses compostos, um mostrou-se mais ativo que o ácido caurenóico, mas também apresentou lise discreta de eritrócitos; outro não apresentou este efeito, mas a atividade não foi aumentada em relação àquela apresentada pelo ácido caurenóico.

Kaurenoic acid, a kauranic diterpenoid, presents in vitro activity against trypomastigote forms of Trypanosoma cruzi, showing, however, lytic activity on blood erythrocytes, as a side effect. The syntheses of twelve new derivatives of kaurenoic acid, four amides, four amines (and three hydroclorides) and four oximes, was carried out aiming at the improvement of the therapeutic activity and without the side effect. Among the derivatives prepared, one compound showed enhanced trypanocidal activity in vitro towards Trypanosoma cruzi trypomastigote erythrocytic forms, when compared to kaurenoic acid, but continued to show discrete lytic activity on erythrocytes; another compound showed a level of activity similar to that of kaurenoic acid, but without lysis.

A monoterpene, 3beta,6beta-dihydroxy-p-menth-1-ene has been isolated from the seeds of Xylopia sericea along with four kaurane, one beyerene, one atisene and four trachylobane diterpenoids, including the trachyloban-18- and 19-methyl esters. The X-ray crystal structure of methyl ent-trachyloban-18-oate was determined in order to make an unambiguous distinction between the 18- and 19-esters. The 13C NMR data for ent-15alpha-hydroxy-trachyloban-19-oic acid has been revised.