Nuevos fármacos inspirados en Annonáceas

Los metabolitos secundarios activos (MSA) juegan un papel importante en el descubrimiento de nuevos medicamentos. Moléculas naturales con esqueletos complejos, tales como las estatinas aisladas de Aspergillus terreus, o las acetogeninas específicas de la familia Annonaceae, no hubieran podido ser inventadas en ningún laboratorio. Los MSA aislados en Annonaceae, especialmente las acetogeninas y los alcaloides isoquinoleínicos, pueden ser considerados como fuente constante de inspiración para químicos, farmacólogos y para todos los investigadores interesados en el descubrimiento de una nueva familia de medicamentos.

Cumarinas e alcaloides de Rauia resinosa (rutaceae)

The genus Rauia, that is poorly chemically studied, belongs to the Rutaceae family. This family has been known to contain a large variety of secondary metabolites. Our phytochemical investigation of the stem and leaves of Rauia resinosa has led to the identification of the structurally related coumarins: murralongin (1), murrangatin (2), munomicrolin (3), murrangatin diacetate (4), umbelliferone (5), rauianin (6) and one novel coumarin: 3-ethylrauianin (7); the alkaloids: N-methyl-4-methoxy-2-quinolone (8), mirtopsine (9), dictamine (10), γ-fagarine (11), skimmianine (12), Z-dimethylrhoifolinate (13), zantodioline (14), zantobungeanine (15), veprissine (16), one novel alkaloid 7-hydroxy-8-methoxy-N-methylflindersine (17) and 8-hydroxy-N-methylflindersine (18) that is described as a natural product for the first time, and a mixture of steroids: as sitosterol and stigmasterol.

Estudo químico e biológico em alcaloides de Hippeastrum aulicum (KER GAWL.) HERB. : uma espécie da família Amaryllidaceae

As espécies da família Amaryllidaceae estão distribuídas em regiões quentes e temperadas ao redor do mundo. Essa família produz um grupo bem conhecido de alcaloides, os isoquinolínicos, que demonstram ampla variedade de atividades biológicas, assim como antiviral, anticâncer, inibição da acetilcolinesterase (AChE), antimalárica, entre outras. Nesse trabalho, são relatados o estudo químico dos alcaloides presentes na espécie brasileira Hippeastrum aulicum e a investigação de atividades antiparasitárias contra Trypanosoma cruzi e Leishmania infantum dos alcaloides isolados. Para tanto, foi realizada extração ácido-base dos extratos metanólicos de bulbos e folhas de H. aulicum, seguida por técnicas cromatográficas de separação, com o objetivo de isolar os alcaloides presentes na espécie. Foram obtidos 11 alcaloides: haemantamina (1), albomaculina (2), haemantidina (3), 6- epihaemantidina (4), N-óxido haemantamina (5), 7-metoxi-O-metillicorenina (6), aulicina (7), licorina (8), trisfaeridina (9), galantina (10) e norpluvina (11). O N-óxido haemantamina é relatado pela primeira vez a partir de fonte natural e nesse trabalho foi totalmente caracterizado por métodos espectrométricos e espectroscópicos. Os alcaloides 1, 2, 6, 7 e 8 foram testados in vitro contra os parasitas Trypanosoma cruzi e Leishmania infantum em diferentes concentrações e haemantamina (1) apresentou-se como importante agente contra a forma promastigota de L. infantum com IC50 de 0,6 M, enquanto 7-metoxi-O-metillicorenina (6) mostrou atividade contra a forma tripomastigota de T.cruzi, sendo mais ativo (IC50 = 89,55 M) e mais seletivo (IS > 2,2) que o padrão utilizado (benzonidazol, IC50 = 440,7 M, IS = 1,0).

Aproximació sintètica d'alcaloides de la família de les Coccinelidae

L’interès per a la síntesi d’alcaloides amb estructura bàsica de perhidro-9b-azafenalè ha augmentat durant els darrers anys, ja que aquesta família d’alcaloides, presents en els coccinèl·lids, poden ser emprats com a mètode biològic en el control de plagues. En el present treball s’ha iniciat l’estudi d’una nova aproximació sintètica als alcaloides amb aquest esquelet. La ruta proposada té com a punt de partida l’Nalquilació enantioselectiva de la glutarimida per a obtenir un alcohol, en base a treballs realitzats amb anterioritat en el nostre grup de recerca. Posteriorment, s’ha realitzat una al·lilació d’un catió acilimini, seguit d’una metàtesi de tancament d’anell, per tal d’obtenir lactames. Finalment , després de tres etapes sintètiques addicionals s’obté l’aminoalcohol bicíclic, el qual ens encamina a la formació del tercer anell present en els alcaloides objectiu 1.

Aproximació sintètica a alcaloides azafenalènics

L’interès per a la síntesi d’alcaloides amb estructura bàsica de perhidro-9b-azafenalè ha augmentat durant els darrers anys, ja que aquesta família d’alcaloides presents en els coccinèl·lids, poden ser emprats com a mètode biològic de control de plagues. En aquest treball s’ha iniciat l’estudi d’una nova aproximació sintètica als alcaloides amb aquest esquelet.

Alcaloides e outros constituintes de Xylopia langsdorffiana (Annonaceae)

The phytochemical investigation of Xylopia langsdorffiana led to the isolation of corytenchine, xylopinine, discretamine, xylopine, ent-atisan-16α-hydroxy-18-oic acid, 13² (S) hydroxy-17³-ethoxyphaephorbide and quercetin-3-α-rhamnoside. Their structures were assigned based on spectroscopic analyses, including two-dimensional NMR techniques. Antioxidant activities of discretamine were measured using the 1,2-diphenyl- 2-picryl-hydrazyl (DPPH) free radical scavenging assay.

Alcaloides iboga de Peschiera affinis (Apocynaceae) - Atribuição inequívoca dos deslocamentos químicos dos átomos de hidrogênio e carbono: atividade antioxidante

Six known alkaloids iboga type and the triterpen α- and β-amyrin acetate were isolated from the roots and stems of Peschiera affinis. Their structures were characterized on the basis of spectral data mainly NMR and mass spectra. 1D and 2D NMR spectra were also used to unequivocal ¹H and 13C chemical shift assignments of alkaloids. The ethanolic extract of roots, alkaloidic and no-alkaloidic fractions and iso-voacristine hydroxyindolenine and voacangine were evaluated for their antioxidative properties using an autographic assay based on β-carotene bleaching on TLC plates, and also spectrophotometric detection by reduction of the stable DPPH (2,2-diphenyl-1-picrylhydrazyl) free radical.

Alcaloides β-indolopiridoquinazolínicos de Esenbeckia grandiflora mart. (Rutaceae)

The chemical composition of two specimens of Esenbeckia grandiflora, collected in the south and northeast regions of Brazil, was investigated. In this study, three β-indolopyridoquinazoline alkaloids from the leaves (rutaecarpine, 1-hydroxyrutaecarpine) and roots (euxylophoricine D) were isolated for the first time in this genus. In addition, the triterpenes α-amyrin, β-amyrin, α-amyrenonol, β-amyrenonol, 3α-hydroxy-ursan-12-one, and 3α-hydroxy-12,13-epoxy-oleanane, the coumarins auraptene, umbelliferone, pimpinelin, and xanthotoxin, the furoquinoline alkaloids delbine and kokusaginine, and the phytosteroids sitosterol, stigmasterol, campesterol and 3β-O-β-D-glucopyranosylsitosterol were also isolated from the leaves, twigs, roots and stems of this species. Structures of these compounds were established by spectral analysis.

Alcaloides indólicos de cascas de Aspidosperma vargasii e A. desmanthum

Fractionation of extracts resulted in isolation and identification of indole alkaloids ellipticine and N-methyltetrahydroellipticine from A. vargasii and aspidocarpine from A. desmanthum. Identification of these compounds was achieved based on IR, MS, ¹H, 13C and 2-D NMR data and comparison to data in the literature.

Cumarinas e alcaloides de Rauia resinosa (rutaceae)

The genus Rauia, that is poorly chemically studied, belongs to the Rutaceae family. This family has been known to contain a large variety of secondary metabolites. Our phytochemical investigation of the stem and leaves of Rauia resinosa has led to the identification of the structurally related coumarins: murralongin (1), murrangatin (2), munomicrolin (3), murrangatin diacetate (4), umbelliferone (5), rauianin (6) and one novel coumarin: 3-ethylrauianin (7); the alkaloids: N-methyl-4-methoxy-2-quinolone (8), mirtopsine (9), dictamine (10), γ-fagarine (11), skimmianine (12), Z-dimethylrhoifolinate (13), zantodioline (14), zantobungeanine (15), veprissine (16), one novel alkaloid 7-hydroxy-8-methoxy-N-methylflindersine (17) and 8-hydroxy-N-methylflindersine (18) that is described as a natural product for the first time, and a mixture of steroids: as sitosterol and stigmasterol.

Mudas de ocotea puberula (lauraceae): identificação e monitoramento de alcaloides aporfinoides

This work describes the occurrence and contents of aporphinoids alkaloids in seedlings of Ocotea puberula from germination until 12 months old and in leaves from adult plants. Seedling leaves showed an alkaloids profile similar to leaves of adult plant. However, leaves in seedlings showed higher contents of the alkaloids boldine, dicentrine, leucoxine and isodomesticine when compared to adult plants. The alkaloids concentration in stems and leaves increased during the development of the seedlings, followed by a remarkable decrease of these compounds in roots. Cultivation in a seedling-nursery method is also described.

Desreplicação de alcaloides aporfínicos e oxoaporfínicos de Unonopsis guatterioides por ESI-IT-MS

The dereplication of aporphine and oxoaporphine alkaloids by direct infusion in ESI-IT-MSn system was applied for alkaloidal fractions of the Unonopsis guatterioides (Annonaceae). Its main advantage over other dereplication methods is the ability to quickly identify substances in complex mixtures without the use of coupled techniques and expensive databases. By only the fragmentation keys and comparison with literature data the aporphine alkaloids anonaine, asimilobine and nornuciferine were identified. The nornuciferine is being reported for the first time in Unonopsis. The oxoaporphine alkaloids liriodenine and lisycamine were identified in the alkaloidal fractions by comparison with the fragmentations of authentic samples.

Alcaloides das cascas das raízes de Zanthoxylum spp

In 1959, Gottlieb and Antonaccio published a study reporting the occurrence of lignan sesamin and triterpene lupeol in Zanthoxylum tingoassuiba. In this work we describe the phytochemical study of the root bark of the Z. tingoassuiba which allowed the identification of the lupeol, sesamin, and alkaloids dihydrochelerythrine, chelerythrine, anorttianamide, cis-N-methyl-canadine, predicentine, 2, 3-methylenedioxy-10,11-dimethoxy-tetrahydro protoberberine. The investigation of hexane and methanol extracts of the root bark of Z. rhoifolium and Z. stelligerum also investigated showed the presence of alkaloids dihydrochelerythrine, anorttianamide, cis-N-methyl-canadine, 7,9-dimethoxy-2,3-methylenedioxybenzophenanthridine and angoline. The occurrence of 2,3-methylenedioxy-10,11-dimethoxy-tetrahydro protoberberine is first described in Z. tingoassuiba and Z. stelligerum. This is also the first report of the presence of hesperidin and neohesperidin in roots of Z. stelligerum.

Aplicação de espectrometria de massas com ionização por elétron na análise de alcaloides do mulungu

Erythrina verna is a medicinal plant used to calm agitation popularly known as mulungu. We purchased the barks of E. verna from a commercial producer and analyzed the alkaloid fraction of the bark by CG-MS and HRESI-MS. Five erythrinian alkaloids were identified: erysotrine, erythratidine, erythratidinone, epimer, and 11-hydroxieritratidinone. Here we report the compound 11-hydroxieritratidinone for the first time as a natural product.

Alcaloides isoquinolínicos e investigação das atividades antiplasmódica e antibacteriana de Guatteria citriodora (Annonaceae)

Phytochemical investigations of the stem bark, leaves and twigs of Guatteria citriodora resulted in the isolation of eight alkaloids: liriodenine, lysicamine, O-methylmoschatoline, 3-methoxyoxoputerine, palmatine, 3-methoxyguadiscidine, guattescidine and oxoputerine. The structures of the isolated substances were established by extensive spectroscopic techniques (1D and 2D NMR) and mass spectrometry (MS), as well as by comparison with data reported in the literature. The in vitro antimalarial activity of the alkaloidal fractions of the leaves and twigs against Plasmodium falciparum FCR3 showed significant results, with IC50 = 1.07 and 0.33 mg mL-1, respectively. The alkaloidal fraction of the leaves showed moderate activity against Enterococcus faecalis, with IC50 = 125.0 mg mL-1. Antiplasmodial and antibacterial activities are attributed to alkaloidal constituents.