RESUMO
RATIONALE: Monoterpene indole alkaloids (MIAs) are a large group of biologically active compounds produced by hundreds of plant species in numerous plant families, such as Apocynaceae, Loganiaceae and Rubiaceae. Although this diversity is biosynthetically intermediated by strictosidine, there are no works focused on the fragmentation patterns under collision-induced dissociation of strictosidine-derived alkaloids. METHODS: Initially, the alkaloid fingerprint of Strychnos peckii was established using leaf spray with tandem mass spectrometry (LS-MS/MS). Then, high-performance liquid chromatography coupled to tandem mass spectrometry (HPLC/MS/MS) analyses were carried out to focus on the patterns of neutral losses in product ion scan experiments with the leaf aqueous extract. Finally, the product ion spectra from a set of presumable strictosidine-type derivatives were analyzed and organized via molecular networking (MN), and dereplicated by manual interpretation of MS/MS spectra. RESULTS: LS-MS/MS allowed the tentative identification of strictosidine-derived alkaloids in the leaves of S. peckii, showing useful neutral losses for the dereplication of strictosidine analogues by HPLC/MS/MS experiments. The use of MN combined with manual interpretation of the fragmentation patterns highlighted characteristic fragmentation pathways, and allowed the tentative identification of strictosidine, desoxycordifoline, strictosidinic acid, 10-hydroxystrictosidine, 5-carboxystrictosidine, lyaloside, 3,4-dehydrostrictosidine and strictosidine lactam. CONCLUSIONS: The use of MN combined with the analysis of the fragmentation patterns proved to be a useful strategy for the dereplication of strictosidine-derived MIAs from S. peckii, highlighting known and unprecedented structures, as well as useful diagnostic product ions. Therefore, this workflow is an effective approach for the characterization of strictosidine-type alkaloids in future dereplication works.
Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Alcaloides de Triptamina e Secologanina/análise , Strychnos/química , Espectrometria de Massas em Tandem/métodos , Curare/química , Folhas de Planta/química , Alcaloides de Triptamina e Secologanina/química , Alcaloides de Triptamina e Secologanina/metabolismo , Processamento de Sinais Assistido por ComputadorRESUMO
Phytochemical investigation of the alkaloid extract of Palicourea sessilis by LC-HRMS/MS using molecular networking and an in silico MS/MS fragmentation approach suggested the presence of several new monoterpene indole alkaloids. These compounds were isolated by semipreparative HPLC, and their structures confirmed by means of HRMS, NMR, and ECD measurements as 4-N-methyllyaloside (3), 4-N-methyl-3,4-dehydrostrictosidine (4), 4ß-hydroxyisodolichantoside (6), and 4α-hydroxyisodolichantoside (7), as well as the known alkaloids alline (1), N-methyltryptamine (2), isodolichantoside (5), and 5-oxodolichantoside (8). In addition, the acetylcholinesterase inhibitory activity of the compounds was evaluated up to 50 µM.
Assuntos
Inibidores da Colinesterase/isolamento & purificação , Rubiaceae/química , Alcaloides de Triptamina e Secologanina/isolamento & purificação , Acetilcolinesterase/efeitos dos fármacos , Brasil , Inibidores da Colinesterase/química , Inibidores da Colinesterase/farmacologia , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular , Folhas de Planta/química , Alcaloides de Triptamina e Secologanina/química , Triptaminas/químicaRESUMO
Three new monoterpene indole alkaloids (1-3) have been isolated from the bark of Geissospermum laeve, together with the known alkaloids (-)-leuconolam (4), geissolosimine (5), and geissospermine (6). The structures of 1-3 were elucidated by analysis of their HRMS and NMR spectroscopic data. The absolute configuration of geissolaevine (1) was deduced from the comparison of experimental and theoretically calculated ECD spectra. The isolation workflow was guided by a molecular networking-based dereplication strategy using an in-house database of monoterpene indole alkaloids. In addition, five known compounds previously undescribed in the Geissospermum genus were dereplicated from the G. laeve alkaloid extract network and were assigned with various levels of identification confidence. The antiparasitic activities against Plasmodium falciparum and Leishmania donovani as well as the cytotoxic activity against the MRC-5 cell line were determined for compounds 1-5.
Assuntos
Antimaláricos/isolamento & purificação , Antiparasitários/isolamento & purificação , Apocynaceae/química , Folhas de Planta/química , Alcaloides de Triptamina e Secologanina/isolamento & purificação , Antimaláricos/química , Antimaláricos/farmacologia , Antiparasitários/química , Antiparasitários/farmacologia , Ensaios de Seleção de Medicamentos Antitumorais , Guiana Francesa , Humanos , Alcaloides Indólicos/química , Leishmania donovani/efeitos dos fármacos , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular , Testes de Sensibilidade Parasitária , Plasmodium falciparum/efeitos dos fármacos , Alcaloides de Triptamina e Secologanina/química , Alcaloides de Triptamina e Secologanina/farmacologiaRESUMO
During comparative analysis on Palicourea species from Costa Rica, two unusual loganin derived tryptamine-iridoid alkaloids were isolated from an accession of Palicourea crocea. Besides the already known brachycerine (2), palicroceaine (1) features a novel hexacyclic backbone. A second provenance, however, yielded strictosidinic acid (3), belonging to the more common secologanin derived tryptamine-iridoid alkaloids, such as those found in Palicourea padifolia. From this species, strictosidine (4), lyaloside (5) and its derivative (E)-O-(6')-(4â³-hydroxy-3â³,5â³-dimethoxy)-cinnamoyl lyaloside (6) could be isolated. A herbarium specimen-based screening was performed, indicating some degree of regional differentiation in alkaloid content and biosynthetic pathways within the widespread and variable Pal. crocea. It further shows its differentiation from the related strictosidine containing Palicourea croceoides. The occurrence of loganin derived tryptamine-iridoid alkaloids in Pal. crocea, Psychotria brachyceras and Psychotria brachypoda, all putatively unrelated members of the Palicourea s.l. clade, is a noteworthy exception within the genus, otherwise largely characterized by secologanin-derived tryptamine-iridoid alkaloids.
Assuntos
Glucosídeos Iridoides/isolamento & purificação , Iridoides/isolamento & purificação , Rubiaceae/química , Alcaloides de Triptamina e Secologanina/química , Alcaloides de Triptamina e Secologanina/isolamento & purificação , Costa Rica , Alcaloides Indólicos , Glucosídeos Iridoides/química , Iridoides/química , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular , Rubiaceae/genéticaRESUMO
Twenty-three indole alkaloids were isolated from Aspidosperma desmanthum and A. spruceanum. Alkaloids 1-4 were isolated from the leaves, 5-8 from the stem bark and 9-15 from the root bark of A. desmanthum. Alkaloids 5, 11, 16, 17 and 19 were isolated from the stem bark, 18 and 20-22 from the root bark and 23 from the flowers of A. spruceanum. Compounds 4, 14, and 15 have not been previously reported as natural products while 16 and 20 have been isolated for the first time from the genus Aspidosperma. Their structures were determined by spectroscopic techniques including 1D and 2D NMR experiments (COSY, NOESY, HSQC, HMBC). The antiparasitic activity of these compounds was tested against Trypanosoma cruzi and Leishmania infantum and their non-specific cytotoxicity on mammalian cells. The most active compounds were 10, 12, 13, and 14 from A. desmanthum, and 19, 21 and 22 from A. spruceanum. Aspidolimine (10) aspidocarpine (12) and tubotaiwine (21) showed selective activity against L. infantum.
Assuntos
Antiparasitários , Aspidosperma , Extratos Vegetais , Alcaloides de Triptamina e Secologanina , Animais , Humanos , Antiparasitários/química , Antiparasitários/isolamento & purificação , Antiparasitários/farmacologia , Aspidosperma/química , Brasil , Linhagem Celular , Células CHO , Cricetulus , Leishmania infantum/efeitos dos fármacos , Leishmaniose Visceral/parasitologia , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/farmacologia , Alcaloides de Triptamina e Secologanina/química , Alcaloides de Triptamina e Secologanina/isolamento & purificação , Alcaloides de Triptamina e Secologanina/farmacologiaRESUMO
Alkaloid fractions of Psychotria suterella (SAE) and Psychotria laciniata (LAE) as well as two monoterpene indole alkaloids (MIAs) isolated from these fractions were evaluated against monoamine oxidases (MAO-A and -B) obtained from rat brain mitochondria. SAE and LAE were analysed by HPLC-PDA and UHPLC/HR-TOF-MS leading to the identification of the compounds 1, 2, 3 and 4, whose identity was confirmed by NMR analyses. Furthermore, SAE and LAE were submitted to the enzymatic assays, showing a strong activity against MAO-A, characterized by IC(50) values of 1.37 ± 1.05 and 2.02 ± 1.08 µg/mL, respectively. Both extracts were also able to inhibit MAO-B, but in higher concentrations. In a next step, SAE and LAE were fractionated by RP-MPLC affording three and four major fractions, respectively. The RP-MPLC fractions were subsequently tested against MAO-A and -B. The RP-MPLC fractions SAE-F3 and LAE-F4 displayed a strong inhibition against MAO-A with IC(50) values of 0.57 ± 1.12 and 1.05 ± 1.15 µg/mL, respectively. The MIAs 1 and 2 also inhibited MAO-A (IC(50) of 50.04 ± 1.09 and 132.5 ± 1.33 µg/mL, respectively) and -B (IC(50) of 306.6 ± 1.40 and 162.8 ± 1.26 µg/mL, respectively), but in higher concentrations when compared with the fractions. This is the first work describing the effects of MIAs found in neotropical species of Psychotria on MAO activity. The results suggest that species belonging to this genus could consist of an interesting source in the search for new MAO inhibitors.
Assuntos
Inibidores da Monoaminoxidase/química , Inibidores da Monoaminoxidase/farmacologia , Psychotria/química , Alcaloides de Triptamina e Secologanina/química , Alcaloides de Triptamina e Secologanina/farmacologia , Animais , Encéfalo/enzimologia , Cromatografia Líquida de Alta Pressão , Relação Dose-Resposta a Droga , Avaliação Pré-Clínica de Medicamentos/métodos , Concentração Inibidora 50 , Masculino , Mitocôndrias/enzimologia , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Ratos , Ratos WistarRESUMO
The present study was designated to evaluate semi-quantitative antileishmanial activity of alkaloidal extracts that were obtained from 1g of different parts of Aspidosperma ramiflorum (leaves, roots, seeds, and stem barks). Alkaloidal extracts of barks and leaves presented a good activity against the extracellular form (promastigotes) of Leishmania (L.) amazonensis. It is known that compounds responsible for the antileishmanial activity in the alkaloidal extracts from A. ramiflorum are the monoterpenoid indole alkaloids ramiflorine A and ramiflorine B, therefore extracts obtained from different plant parts were analyzed by electrospray ionization mass spectrometry (ESI-MS) in order to evidence the presence of these bioactive alkaloids. Based on these findings, alkaloidal extract from leaves was fractionated on preparative thin-layer chromatography in a bioassay-guided fractionation affording individual purified ramiflorines A and B. Both ramiflorines A and B showed significant activity against Leishmania (L.) amazonensis (LD(50) values of 18.5±6.5µg/ml and 12.63±5.52µg/ml, respectively). Our results are showing that alkaloidal extract from leaves is a promising alternative to the use of stem barks from A. ramiflorum.
Assuntos
Alcaloides/farmacologia , Aspidosperma/química , Leishmania/efeitos dos fármacos , Extratos Vegetais/farmacologia , Folhas de Planta/química , Alcaloides/química , Alcaloides/isolamento & purificação , Bioensaio , Cromatografia em Camada Fina , Casca de Planta/química , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Raízes de Plantas/química , Alcaloides de Triptamina e Secologanina/química , Alcaloides de Triptamina e Secologanina/isolamento & purificação , Alcaloides de Triptamina e Secologanina/farmacologia , Sementes/química , Espectrometria de Massas por Ionização por ElectrosprayRESUMO
The methanolic extract of Tabernaemontana catharinensis (Apocynaceae) roots, which contains alkaloids with several biological activities, was separated on a preparative scale using high-speed counter-current chromatography. The optimum solvent system was found to be a mixture of CHCl(3)-MeOH-H(2)O [5:10:6 (v/v/v)] and led to a successful separation of two monoterpenic indole alkaloids, voachalotine (1) and 12-methoxy-N(b)-methylvoachalotine (2) in approximately 4.0 hours. The alkaloids were all isolated at purities over 95%, and their structures were established on the basis of spectroscopic methods, including 1D and 2D NMR and EI/MS.