RESUMO
Schizanthus grahamii is an endemic Chilean plant that is known to contain tropane alkaloids. Five new alkaloids, grahamines A-E (1-5), were isolated and characterized by extensive spectroscopic analysis. Their structures were determined to be 2-{[(3α-hydroxytropo-6ß-yl)oxy]carbonyl}-2-methyl-3-{[((6ß-angeloyloxy)-3α-yl)oxy]carbonyl}-4-phenylcyclobutanecarboxylic acid (1), 2-{[(3α-hydroxytropo-6ß-yl)oxy]carbonyl}-2-methyl-3-{[((6ß-tigloyloxy)-3α-yl)oxy]carbonyl}-4-phenylcyclobutanecarboxylic acid (2), 1-methyl-2-{[(3α-hydroxytropo-6ß-yl)oxy]carbonyl}-4-{[((6ß-angeloyloxy)-3α-yl)oxy]carbonyl}-3-phenylcyclobutanecarboxylic acid (3), 1,2-bis{[(3α-hydroxytropo-6ß-yl)oxy]carbonyl}-2-methyl-3-{[((6ß-angeloyloxy)-3α-yl)oxy]carbonyl}-4-phenylcyclobutanecarboxylate (4), and 1-{[(3α-mesaconyloxytropo-6ß-yl)oxy]carbonyl}-2-{[(3α-hydroxytropo-6ß-yl)oxy]carbonyl}-2-methyl-3-{[((6ß-angeloyloxy)-3α-yl)oxy]carbonyl}-4-phenylcyclobutanecarboxylate (5).
Assuntos
Alcaloides/isolamento & purificação , Ciclobutanos/química , Solanaceae/química , Tropanos/isolamento & purificação , Alcaloides/química , Chile , Estrutura Molecular , Estereoisomerismo , Tropanos/químicaRESUMO
Three tropane alkaloids, named schizanthines N, O, and P (1-3), have been isolated from the crude alkaloid extract of the endemic Chilean plant Schizanthus tricolor. On the basis of extensive NMR studies and MS fragmentation analysis, their structures were determined to be 3α-(E)-4-hydroxysenecioyloxy-6ß-angeloyloxytropane (1), 3α-(E)-4-hydroxysenecioyloxy-6ß-senecioyloxytropane (2), and 3α-mesaconyloxy-6ß-senecioyloxytropane (3). Compounds 1 and 2 are the first isomeric alkaloids in the tropane series possessing a hydroxysenecioyl substituent as an esterifying moiety.
Assuntos
Alcaloides/isolamento & purificação , Solanaceae/química , Tropanos/isolamento & purificação , Alcaloides/química , Chile , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular , Estereoisomerismo , Tropanos/químicaRESUMO
Investigation of the aerial parts of Schizanthus tricolor yielded seven isomeric tropane alkaloids: 3alpha-(1-methylitaconyl)-6beta-senecioyloxytropane (1), 3alpha-(1-methylitaconyl)-6beta-angeloyloxytropane (2), 3alpha-(1-methylmesaconyl)-6beta-senecioyloxytropane (3), 3alpha-(1-methylmesaconyl)-6beta-angeloyloxytropane (4), 3alpha-(1-methylmesaconyl)-6beta-tigloyloxytropane (5), 3alpha-(1-methylcitraconyl)-6beta-senecioyloxytropane (6), and 3alpha-(1-methylcitraconyl)-6beta-angeloyloxytropane (7). Their structures were established by NMR including (1)H, (13)C NMR, HSQC, HMBC, COSY, and NOESY experiments, UV, IR, and mass spectrometry. Compounds 1, 6, and 7 are new to the literature. Alkaloids 1, 3, 4, and 5 and a mixture of 3, 4, and 5 were evaluated for in vitro antiplasmodial and cytotoxic activity. Compounds 1, 4, and 5 showed marginal inhibition of Plasmodium falciparum strain K1 with IC(50) values of 22.8, 24.8, and 36.0 microM and displayed no cytotoxicity on MRC-65 cells (CC(50) > 64 microM). Alkaloid 3 was inactive (IC(50) 63.5 microM). The alkaloid mixture exhibited slightly higher activity (IC(50) 17.0 microM) than the pure compounds, indicating some synergy between the different isomers.
Assuntos
Alcaloides/isolamento & purificação , Antimaláricos/isolamento & purificação , Plantas Medicinais/química , Plasmodium falciparum/efeitos dos fármacos , Solanaceae/química , Tropanos/isolamento & purificação , Alcaloides/química , Alcaloides/farmacologia , Antimaláricos/química , Antimaláricos/farmacologia , Chile , Humanos , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular , Estereoisomerismo , Tropanos/química , Tropanos/farmacologiaRESUMO
A rapid in vitro propagation system leading to formation of shoots from callus, roots, and plantlets was developed for Schizanthus hookeri Gill. (Solanaceae), an endemic Chilean plant. The genus Schizanthus is of particular interest due to the presence of several tropane alkaloids. So far, in vitro propagation of species of this genus has not been reported. Propagation of S. hookeri consisted of two phases, the first one for callus initiation and shoot formation and the second for rhizogenesis and plantlet regeneration. From a single callus that rapidly increased in cell biomass (from approximately 50 mg to approximately 460 mg/culture tube [25 x 130 mm] in 60 days) in the presence of 2.69 microM NAA and 2.22 microM BA, more than 10 shoots/callus explant were formed. From the latter, approx. twenty plantlets formed after 90-110 days shoot subculture in medium devoid of growth regulators that favored root formation. Ten alkaloids ranging from simple pyrrolidine derivatives to tropane esters derived from angelic, tiglic, senecioic or methylmesaconic acids were obtained from in vitro regenerated plantlets. One of them, 3alpha-methylmesaconyloxytropane, was not previously described. The same growth conditions, as well as other growth regulator levels tested, were required to induce callus and root formation in S. grahamii Gill. Root organogenesis occurred despite a high level of BA vs. NAA used, (i.e., 4.44 microM BA and 0.54 microM NAA); however no shoot formation was achieved. In the case of S. tricolor Grau et Gronbach, only callus formation was obtained in the presence of various growth regulators.