P. C. Vieira

Structure of Trypanosoma cruzi glycosomal glyceraldehyde-3-phosphate dehydrogenase complexed with chalepin, a natural product inhibitor, at 1.95 Å resolution

The structure of the glycosomal glyceraldehyde‐3‐phosphate dehydrogenase (gGAPDH) from Trypanosoma cruzi complexed with chalepin, a natural product from Pilocarpus spicatus, has been determined by X‐ray crystallography to 1.95 Å resolution. The structure is in the apo form without cofactors in the subunits of the tetrameric gGAPDH in the asymmetric unit. Unequivocal density corresponding to the inhibitor was clearly identified in one monomer. The final refined model of the complex shows extensive conformational changes when compared with the native structure. The mode of binding of chalepin to gGAPDH and its implications for inhibitor design are discussed.

Toxicity of lignans to symbiotic fungus of leaf-cutting ants

Lignans fromVirola sebifera Aubl.,Virola sp., andOtoba parvifolia (Mkfg.) A. Gentry (Myristicaceae) inhibited the in vitro growth of the fungus cultivated by leaf-cutting ants of the speciesAtta sexdens rubropilosa Forel (Hymenoptera: Formicidae). A comparison of activity among the lignans was obtained.

In vitro cytotoxicity activity on several cancer cell lines of acridone alkaloids and N -phenylethyl-benzamide derivatives from Swinglea glutinosa (Bl.) Merr.

The methanol extract from the stems and fruits of Swinglea glutinosa (Rutaceae) afforded 11 known acridone alkaloids and three N-phenylethyl-benzamide derivatives, glycocitrine-IV, 1,3,5-trihydroxy-4-methoxy-10-methyl-2,8-bis(3-methylbut-2-enyl)acridin-9(10H)-one, 1,3,5- trihydroxy-2,8-bis(3-methylbut-2-enyl)-10-methyl-9-acridone, citbrasine, citrusinine-II, citrusinine-I, 5-dihydroxyacronycine, pyranofoline, 3,4-dihydro-3,5,8-trihydroxy-6-methoxy-2,2,7-trimethyl-2H-pyrano[2,3-a]acridin-12(7H)-one, 2,3-dihydro-4,9-dihydroxy-2-(2-hydroxy-propan-2-yl)-11-methoxy-10-methylfuro[3,2-b]acridin-5(10H)-one, bis-5-hydroxyacronycine, N-(2-{4-[(3,7-dimethylocta-2,6-dien-1-yl)oxy]phenyl}ethyl)benzamide, N-(2-{4-[(3,7-dimethyl-4-acethyl-octa-2,6-dien-1-yl)oxy]phenyl}ethyl)benzamide, and severine acetate. All compounds isolated were examined for their activity against three cancer cell lines: human lung carcinoma (COR-L23), human breast adenocarcinoma (MCF7), human melanoma (C32), and normal human fetal lung cell line, MRC-5. The acridones tested exhibited weak cytotoxicity but the amides showed moderate nonselective cytotoxic activity.

Antiparasitic activities of acridone alkaloids from Swinglea glutinosa (Bl.) Merr.

Onze alcaloides acridonicos isolados de Swinglea glutinosa (Bl.) Merr. foram avaliados para suas atividades in vitro contra linhagens de Plasmodium falciparum sensiveis a cloroquina 3D7, Trypanosoma brucei rhodesiense STIB9000 e Leishmania donovani L82. Ensaios com celulas KB foram tambem executados com o objetivo de se determinar o grau de toxicidade das substâncias ativas contra os parasitas. Nove dos compostos apresentaram IC 50 entre 0,3 e 11,6 µM contra P. falciparum. Em contraste, um pequeno numero de compostos mostrou atividade significativa contra T. brucei rhodesiense e nenhum apresentou atividade contra L. donovani. Entre os alcaloides tres tiveram IC 50 < 1,0 µM contra P. falciparum, enquanto que contra T. b. rhodesiense cinco mostraram IC 50 < 10 µM. A caracterizacao dos alcaloides, 1,3,5-triidroxi-4-metoxi-10-metil-2,8bis(3-metilbut-2-enil)acridin-9(10H)-ona (1), 2,3-diidro-4,9-diidroxi-2-(2-hidroxipropan-2-il)11-metoxi-10-metilfuro[3,2-b]acridin-5(10H)-ona (2) e 3,4-diidro-3,5,8-triidroxi-6-metoxi-2,2,7trimetil-2H-pirano[2,3-a]acridin-12(7H)-ona (3), e aqui discutida. Discute-se tambem a relacao estrutura-atividade para todos os compostos ensaiados. O isolamento e dados espectrais para os alcaloides 1-3 estao sendo aqui descritos pela primeira vez, embora em trabalho anterior tenham sido relatadas as suas atividades citotoxicas. Eleven acridone alkaloids isolated from Swinglea glutinosa (Bl.) Merr. were examined for in vitro activity against chloroquine-sensitive Plasmodium falciparum 3D7, Trypanosoma brucei rhodesiense STIB900 and Leishmania donovani L82. An assay with KB cells was developed in order to compare in vitro toxicity of alkaloids with the selective action on the parasites. Nine of the compounds had IC 50 values ranging from 0.3 to 11.6 µM against P. falciparum. In contrast, a small number of compounds showed significant activity against T. brucei rhodesiense and none had activity against L. donovani. Among the alkaloids three had IC 50 < 1.0 µM against P. falciparum, whereas against T. b. rhodesiense five had IC 50 < 10 µM. The characterization of the acridone alkaloids, 1,3,5-trihydroxy-4-methoxy-10-methyl-2,8-bis(3-methylbut-2-enyl)acridin-9(10H)-one (1), 2,3-dihydro-4,9-dihydroxy-2-(2-hydroxypropan-2-yl)-11-methoxy-10-methylfuro[3,2-b] acridin-5(10H)-one (2) and 3,4-dihydro-3,5,8-trihydroxy-6-methoxy-2,2,7-trimethyl-2Hpyrano[2,3-a]acridin-12(7H)-one (3), is discussed, as well as the structure-activity relationship of all compounds assayed. Isolation and spectral data of alkaloids 1-3 are described for the first time although their citotoxicities to cancer cells have been described before.

Behavioral changes in workers of the leaf-cutting ant Atta sexdens rubropilosa induced by chemical components of Eucalyptus maculata leaves.

The response of Atta sexdens rubropilosa Forel workers to essential oils, epicuticular wax and hexane, dichloromethane, ethyl acetate, and methanol extracts of Eucalyptus maculata was evaluated. Hexane extracts of E. maculata interfered with the recognition mechanism among workers. The main active compounds identified from this plant were the sesquiterpenes elemol and β-eudesmol. These compounds may be responsible for the resistance of this species to ant attack.

Dihydrochalcones, coumarins and alkaloids from Metrodorea nigra

Abstract Two novel dihydrochalcones, 2′,3,4′,6′-tetrahydroxy-4-methoxy-3′,5-di-(3,3-dimethylallyl)-dihydrochalcone and 2′,.3,6′-trihydroxy-4-methoxy-5-(3,3-dimethylallyl)-3′,4′-(2″,2″-dimethyldihydropyran)-dihydrochalcone, have been isolated from fresh fruits of Metrodorea nigra . Stems and leaves showed a similar composition and we have isolated common steroids, simple coumarins, several furocoumarins, furoquinoline alkaloids and a furofuran lignan. From stems, we have also isolated the pentacyclic 6- C -monoterpenyl-5,7-dioxycoumarin, deoxybruceol. Structures of the isolated compounds were elucidated on the basis of spectral data.

Synthetic amides toxic to the leaf‐cutting ant Atta sexdens rubropilosa L. and its symbiotic fungus

1 Nine synthetic amides similar to natural N‐piperidine‐3‐(4,5‐methylenedioxyphenyl)‐2‐(E)‐propenamide and N‐pyrrolidine‐3‐(4,5‐methylenedyoxiphenyl)‐2‐(E)‐propenamide were synthesized and identified by their spectroscopic data. 2 The toxicity of these synthetic amides to the Atta sexdens rubropilosa workers and the antifungal activity against Leucoagaricus gongylophorus, the symbiotic fungus of the leaf‐cutting ants, were determined. 3 Workers ants that were fed daily on an artificial diet to which these compounds were added had a higher mortality rate than the controls for N‐pyrrolidine‐3‐(3′,4′‐methylenedioxyphenyl)‐2‐(E)‐propenamide and N‐benzyl‐3‐(3′,4′‐methylenedioxyphenyl)‐2‐(E)‐propenamide at a concentration of 100 µg/mL. 4 The completely inhibition (100%) of the fungal growth was observed with N‐piperidine‐3‐(3′,4′‐methylenedioxyphenyl)‐2‐(E)‐propenamide and N,N‐diethyl‐3‐(3′,4′‐methylenedioxyphenyl)‐2‐(E)‐propenamide at concentrations of 50 and 100 µg/mL and N‐pirrolidine‐3‐(3′,4′‐methylenedioxyphenyl)‐2‐(E)‐propenamide at a concentration of 100 µg/mL. 5 The possibility of controlling these insects in the future using synthetic piperamides that can simultaneously target both organisms is discussed.

Frações de Trichilia pallens com atividade inseticida sobre Tuta absoluta

This work aimed at identifying fractions of aqueous and organic extracts of the meliaceous Trichilia pallens with insecticidal activity against the tomato leafminer Tuta absoluta (Meyrick). Leaf and twig freeze-dried aqueous extracts (FDA) of T. pallens were resuspended in water at a concentration of 3% and sprayed over tomato leaflets, which were infested with newly-hatched larvae. Larval mortality at 5 and 10 days after infestation (dai) were higher for leaf extracts. In a second set of experiments, 1% leaf extracts were produced by maceration in hexane (HEX), dichloromethane (DIC) and methanol (MET), and tested as described before, using acetone and water as controls. DIC extracts were the most promising as a source of substances with insecticidal activity against T. absoluta larvae, and were further processed and subjected to partition assays, producing fractions in HEX, MET, ethyl acetate (ETA), n-butanol (NBU) and water (WA). After testing, 0.1% WA fraction, obtained from the partition assay of DIC extracts showed the highest insecticidal activity against T. absoluta.

Unequivocal NMR assignments: O-methoxy-methyl esters derivatives of acid chromanones from Calophyllum brasiliense CAMB. (Guanandi).

The present work describes the fractionation of the crude hexane extract (EBHEX) from Calophyllum brasiliense (Clusiaceae) stem bark. Derivatization of DCM2-9 fraction with diazomethane afforded the chromanones inophylloidic acid, isobrasiliensic acid, as well as, a mixture containing isobrasiliensic and brasiliensic acids, in the form of their more stable O-methoxy-methyl esters derivatives 1, 2, and 3, respectively. The isolation of 1 from C. brasiliense is described for the first time herein. The use of two-dimensional NMR methods (1H-COSY, HMQC, and HMBC) allowed the precise determination of 13C and 1H chemical shifts of compounds 1, 2, and 3.

Alkaloids and triterpene from Almeidea coerulea (Nees and Mart.) a. St.-Hil. and anti-leishmanial activity

The dichloromethane extract of Almeidea coerulea stems yielded the (11-hydroxyrutaecarpine alkaloid reported for the first time from this species) and the triterpene (28-hydroxy-28, 29-dihydrolupeol). The dictamine, skimianine, sitosterol and stigmasterol were also isolated from methanol extract. Extracellular forms of Leishmania amazonensis (promastigotes) was tested with dichloromethane extract and 28-hydroxy-28, 29-dihydrolupeol with showed anti-leishmanial activity above 0.1 mg/mL and 75µg/mL (inhibited 50% promastigote growth), respectively.