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1.
J Nat Med ; 75(2): 408-414, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33462757

RESUMO

Two new bisindole alkaloids, 12'-O-demethyl-vobtusine-5-lactam and isovobtusine-N-oxide (1 and 2), were isolated from the leaves of Voacanga grandifolia, together with two known bisindole alkaloids. Their structures were elucidated on the basis of 1D and 2D NMR data. 1 and 2 showed potent antimalarial activity against Plasmodium falciparum 3D7 and very low cytotoxic activity against a human cell line, HepG2 cells.


Assuntos
Alcaloides Indólicos/química , Folhas de Planta/química , Voacanga/química , Humanos , Estrutura Molecular
2.
Phytochemistry ; 181: 112566, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33197743

RESUMO

Fourteen undescribed monoterpenoid indole alkaloids, voacafrines A-N, along with 7 known monoterpenoid indole alkaloids were isolated from the seeds of Voacanga africana Stapf. Among them, voacafrines A-G were aspidosperma-aspidosperma type bisindole alkaloids, while voacafrines H-N were aspidosperma-type monomers. Their structures and absolute configurations were elucidated by a combination of NMR, MS, and ECD analyses. Voacafrines A-C were characterized by an acetonyl moiety at C-5', while voacafrine H possessed a methoxymethyl moiety at C-14 within aspidosperma-type alkaloids. The acetylcholinesterase (AChE) inhibitory activity and cytotoxicity of voacafrines A-N were evaluated. Voacafrines A-C and E-G were bisindole alkaloids that exhibited AChE inhibitory activity with IC50 values of 4.97-33.28 µM, while voacafrines I and J were monomers that showed cytotoxicity against several human cancer cell lines with IC50 values of 4.45-7.49 µM.


Assuntos
Aspidosperma , Alcaloides de Triptamina e Secologanina , Voacanga , Alcaloides Indólicos/farmacologia , Estrutura Molecular , Alcaloides de Triptamina e Secologanina/farmacologia
3.
Molecules ; 26(1)2020 Dec 25.
Artigo em Inglês | MEDLINE | ID: mdl-33375687

RESUMO

A new iboga-vobasine-type isomeric bisindole alkaloid named voacamine A (1), along with eight known compounds-voacangine (2), voacristine (3), coronaridine (4), tabernanthine (5), iboxygaine (6), voacamine (7), voacorine (8) and conoduramine (9)-were isolated from the stem bark of Voacangaafricana. The structures of the compounds were determined by comprehensive spectroscopic analyses. Compounds 1, 2, 3, 4, 6, 7 and 8 were found to inhibit the motility of both the microfilariae (Mf) and adult male worms of Onchocerca ochengi, in a dose-dependent manner, but were only moderately active on the adult female worms upon biochemical assessment at 30 µM drug concentrations. The IC50 values of the isolates are 2.49-5.49 µM for microfilariae and 3.45-17.87 µM for adult males. Homology modeling was used to generate a 3D model of the O. ochengi thioredoxin reductase target and docking simulation, followed by molecular dynamics and binding free energy calculations attempted to offer an explanation of the anti-onchocercal structure-activity relationship (SAR) of the isolated compounds. These alkaloids are new potential leads for the development of antifilarial drugs. The results of this study validate the traditional use of V. africana in the treatment of human onchocerciasis.


Assuntos
Alcaloides/química , Onchocerca/efeitos dos fármacos , Oncocercose/tratamento farmacológico , Voacanga/química , Alcaloides/farmacologia , Animais , Humanos , Onchocerca/patogenicidade , Oncocercose/parasitologia
4.
Chem Biodivers ; 17(5): e2000002, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32232967

RESUMO

In continuation of our efforts to provide quantitative information on antiaddictive ibogan type alkaloid-producing Tabernaemontana species, we used gas chromatography-mass spectrometry (GC/MS) to compare the alkaloid profiles of the barks and/or leaves of one Mexican and one African species - T. arborea and T. crassa, respectively, with the primary sources of commercially available semisynthetic ibogaine, Voacanga africana root and stem bark. The qualitative and quantitative similarities between T. arborea and V. africana barks consolidate previous reports regarding the potential of the former as a promising alternative source of voacangine and ibogaine. The results also suggest that T. crassa could be used to produce conopharyngine and ibogaline, two compounds with the same basic skeletal structure and possibly similar antiaddictive properties as ibogaine.


Assuntos
Ibogaína/química , Tabernaemontana/química , Voacanga/química , Gana , Ibogaína/análogos & derivados , México , Conformação Molecular , Especificidade da Espécie
5.
Nat Prod Res ; 33(23): 3459-3463, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29852800

RESUMO

One known bis-indole alkaloid-voacamine was isolated from Voacanga africana Stapf and Surface Plasmon Resonance imaging (SPRi) exprement showed that this alkaloid could be combine with Protein Tyrosine Phosphatase1B (PTP1B). Then the PTP1B activity inhibition experiment display that the compound showed an outstanding promoting activity to PTP1B.


Assuntos
Ibogaína/análogos & derivados , Proteína Tirosina Fosfatase não Receptora Tipo 1/antagonistas & inibidores , Ressonância de Plasmônio de Superfície/métodos , Voacanga/química , Alcaloides/isolamento & purificação , Alcaloides/farmacologia , Humanos , Ibogaína/isolamento & purificação , Indóis
6.
Sci Rep ; 8(1): 10617, 2018 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-30006510

RESUMO

The jerantinine family of Aspidosperma indole alkaloids from Tabernaemontana corymbosa are potent microtubule-targeting agents with broad spectrum anticancer activity. The natural supply of these precious metabolites has been significantly disrupted due to the inclusion of T. corymbosa on the endangered list of threatened species by the International Union for Conservation of Nature. This report describes the asymmetric syntheses of (-)-jerantinines A and E from sustainably sourced (-)-tabersonine, using a straight-forward and robust biomimetic approach. Biological investigations of synthetic (-)-jerantinine A, along with molecular modelling and X-ray crystallography studies of the tubulin-(-)-jerantinine B acetate complex, advocate an anticancer mode of action of the jerantinines operating via microtubule disruption resulting from binding at the colchicine site. This work lays the foundation for accessing useful quantities of enantiomerically pure jerantinine alkaloids for future development.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Alcaloides Indólicos/farmacologia , Tubulina (Proteína)/metabolismo , Antineoplásicos Fitogênicos/síntese química , Linhagem Celular Tumoral , Colchicina/farmacologia , Cristalografia por Raios X , Ensaios de Seleção de Medicamentos Antitumorais , Espécies em Perigo de Extinção , Química Verde , Humanos , Alcaloides Indólicos/síntese química , Alcaloides Indólicos/química , Alcaloides Indólicos/isolamento & purificação , Microtúbulos/química , Microtúbulos/efeitos dos fármacos , Microtúbulos/metabolismo , Modelos Moleculares , Quinolinas/química , Quinolinas/isolamento & purificação , Sementes/química , Tabernaemontana/química , Tubulina (Proteína)/química , Moduladores de Tubulina/farmacologia , Voacanga/química
7.
Org Lett ; 20(9): 2702-2706, 2018 05 04.
Artigo em Inglês | MEDLINE | ID: mdl-29676579

RESUMO

Voacafricines A and B, two unique monoterpenoid indole alkaloids each bearing five fused heterocycles, were obtained from the fruits of Voacanga africana. Their structures were elucidated by extensive spectroscopic methods and computational studies. A plausible biogenetic pathway was proposed from a common precursor, 19- epi-voacristine. Both compounds exhibited potent activity against Staphylococcus aureus and Salmonella typhi, and their activities were superior to those of the well-known antibacterial drugs berberine and fibrauretine.


Assuntos
Voacanga , Antibacterianos , Estrutura Molecular , Alcaloides de Triptamina e Secologanina
8.
Planta Med ; 82(11-12): 1030-8, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-27257769

RESUMO

Herbal preparations from Voacanga africana are used in West and Central African folk medicine and are also becoming increasingly popular as a legal high in Europe. Recently, the main alkaloid voacangine was found to be a potent human ether-à-go-go-related gene channel blocker in vitro. Blockage of this channel might imply possible cardiotoxicity. Therefore, the aim of this study was to characterise voacangine in vivo to assess its pharmacokinetics and to estimate if further studies to investigate its cardiotoxic risk are required. Male Wistar rats received different doses of voacangine as a pure compound and as a hydro-ethanolic extract of V. africana root bark with a quantified amount of 9.71 % voacangine. For the obtained data, a simultaneous population pharmacokinetics model was successfully developed, comprising a two-compartment model for i. v. dosing and a one-compartmental model with two first-order absorption rates for oral dosing. The absolute bioavailability of voacangine was determined to be 11-13 %. Model analysis showed significant differences in the first absorption rate constant for voacangine administered as a pure compound and voacangine from the extract of V. africana. Taking into account the obtained low bioavailability of voacangine, its cardiotoxic risk might be neglectable in healthy consumers, but may have a serious impact in light of drug/drug interactions and impaired health conditions.


Assuntos
Canais de Potássio Éter-A-Go-Go/antagonistas & inibidores , Ibogaína/análogos & derivados , Voacanga/química , Animais , Humanos , Ibogaína/química , Ibogaína/farmacocinética , Ibogaína/farmacologia , Masculino , Estrutura Molecular , Ratos , Ratos Wistar , Espectrometria de Massas em Tandem/métodos
9.
Nat Prod Res ; 30(10): 1144-9, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26140390

RESUMO

A new monoterpenoid indole alkaloid compound (1) and six known monoterpenoid indole alkaloids compounds (2-7) were isolated from the barks of Voacanga africana Staph. The structures were established by spectral analysis as ibogamine-16-carboxylic acid,17,20-didehydro-5,6-dioxo-10-methoxy-methyl ester (1), voacamine (2), vobasine (3), voacangine (4), voacristine (5), 19-epi-voacristine (6) and 19-epi-heyneanine (7). Compound 1 was confirmed by X-ray crystallographic analysis. All of the isolated compounds were evaluated for cytotoxicity against five cell lines (HEPG-2, A375, MDA-MB-231, SH-SY5Y, CT26). Among them, compounds 2 and 6 displayed significant inhibitory activities, compounds 3, 4 and 5 showed moderate inhibitory activities, while compounds 1 and 7 showed no inhibitory activities against the five cell lines.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Alcaloides de Triptamina e Secologanina/isolamento & purificação , Alcaloides de Triptamina e Secologanina/farmacologia , Voacanga/química , Antineoplásicos Fitogênicos/isolamento & purificação , Hidrocarbonetos Aromáticos com Pontes/isolamento & purificação , Hidrocarbonetos Aromáticos com Pontes/farmacologia , Linhagem Celular Tumoral/efeitos dos fármacos , Humanos , Ibogaína/análogos & derivados , Ibogaína/isolamento & purificação , Alcaloides Indólicos/isolamento & purificação , Estrutura Molecular , Casca de Planta/química
10.
Nat Prod Res ; 29(20): 1950-3, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25686854

RESUMO

In this study, essential oils from Voacanga africana seeds at different extraction stages were investigated. In the chemical composition analysis, 27 compounds representing 86.69-95.03% of the total essential oils were identified and quantified. The main constituents in essential oils were terpenoids, alcohols and fatty acids accounting for 15.03-24.36%, 21.57-34.43% and 33.06-57.37%, respectively. Moreover, the analysis also revealed that essential oils from different extraction stages possessed different chemical compositions. In the antioxidant evaluation, all analysed oils showed similar antioxidant behaviours, and the concentrations of essential oils providing 50% inhibition of DPPH-scavenging activity (IC50) were about 25 mg/mL. In the antimicrobial experiments, essential oils from different extraction stages exhibited different antimicrobial activities. The antimicrobial activity of oils was affected by extraction stages. By controlling extraction stages, it is promising to obtain essential oils with desired antimicrobial activities.


Assuntos
Anti-Infecciosos/química , Sequestradores de Radicais Livres/química , Óleos Voláteis/química , Sementes/química , Voacanga/química , Anti-Infecciosos/isolamento & purificação , Sequestradores de Radicais Livres/isolamento & purificação , Cromatografia Gasosa-Espectrometria de Massas , Testes de Sensibilidade Microbiana , Extratos Vegetais/química , Óleos Vegetais/química
11.
Asian Pac J Cancer Prev ; 15(2): 617-22, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24568467

RESUMO

Voacanga globosa (Blanco), a plant endemic to the Philippines, is traditionally used especially by indigenous people of Bataan in the treatment of ulcers, wounds and tumorous growths. This study aimed to provide scientific evidence to therapeutic properties by determining cytotoxic and pro-apoptotic activity of HPLC fractions from leaves on HCT116 human colon carcinoma and A549 human lung carcinoma cell lines. Ethanolic extraction was performed on V globosa leaves followed by hexane and ethyl acetate partitioning. Silica gel column chromatography and high performance liquid chromatography (HPLC) produced MP1, MP2 and MP3 fractions. Cytotoxic activity of the fractions was determined through MTT assay against the cancer cell lines HCT116 and A549 and the non-cancer AA8 Chinese hamster ovarian cell line. Pro-apoptotic activities of the most active fractions were further assessed through DAPI staining, TUNEL assay and JC-1 mitochondrial membrane potential assay with HCT116 cells. While the MP1 fraction exerted no significant activity against all cell lines tested, MP2 and MP3 fractions demonstrated high toxicity against HCT116 and A549 cells. The MP3 fraction induced formation of apoptotic bodies, condensed DNA and other morphological changes consistent with apoptosis of HCT116 cells and TUNEL assay showed significant increase in DNA fragmentation over time. In these cells, the MP3 fraction also induced mitochondrial membrane destabilization, which is generally associated with the beginning of apoptosis. Phytochemical analysis demonstrated the presence only of saponins and terpenoids in the MP3 fraction. The results indicate that the MP3 fraction exerts cytotoxic activity on HCT116 cells via induction of apoptosis triggered by loss of mitochondrial membrane potential crucial for cell survival.


Assuntos
Apoptose/efeitos dos fármacos , Cromatografia Líquida de Alta Pressão/métodos , Neoplasias do Colo/tratamento farmacológico , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Extratos Vegetais/farmacologia , Folhas de Planta/química , Voacanga/química , Animais , Células CHO , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Neoplasias do Colo/enzimologia , Neoplasias do Colo/patologia , Cricetinae , Cricetulus , Humanos
12.
J Nat Prod ; 77(2): 285-97, 2014 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-24484240

RESUMO

Voacangine (1) is an alkaloid found in the root bark of Voacanga africana. Our previous work has suggested that 1 is a novel transient receptor potential vanilloid type 1 (TRPV1) antagonist. In this study, the agonist and antagonist activities of 1 were examined against thermosensitive TRP channels. Channel activity was evaluated mainly using TRP channel-expressing HEK cells and calcium imaging. Herein, it was shown that 1 acts as an antagonist for TRPV1 and TRPM8 but as an agonist for TRPA1 (EC50, 8 µM). The compound competitively blocked capsaicin binding to TRPV1 (IC50, 50 µM). Voacangine (1) competitively inhibited the binding of menthol to TRPM8 (IC50, 9 µM), but it showed noncompetitive inhibition against icilin (IC50, 7 µM). Moreover, the compound selectively abrogated chemical agonist-induced TRPM8 activation and did not affect cold-induced activation. Among these effects, the TRPM8 inhibition profile is unique and noteworthy, because to date no studies have reported a menthol competitive inhibitor of TRPM8 derived from a natural source. Furthermore, this is the first report of a stimulus-selective TRPM8 antagonist. Accordingly, 1 may contribute to the development of a novel class of stimulus-selective TRPM8 blockers.


Assuntos
Alcaloides/farmacologia , Ibogaína/análogos & derivados , Canais de Potencial de Receptor Transitório/agonistas , Canais de Potencial de Receptor Transitório/antagonistas & inibidores , Voacanga/química , África , Alcaloides/química , Alcaloides/isolamento & purificação , Cálcio/metabolismo , Capsaicina/farmacologia , Humanos , Ibogaína/química , Ibogaína/isolamento & purificação , Ibogaína/farmacologia , Mentol/farmacologia , Estrutura Molecular , Casca de Planta/química , Pirimidinonas/farmacologia , Canais de Cátion TRPV , Canais de Potencial de Receptor Transitório/metabolismo , Árvores/química
13.
Org Lett ; 14(22): 5800-3, 2012 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-23131084

RESUMO

A new hexacyclic iboga-type indole alkaloid, voacangalactone (1), was isolated from Voacanga africana , and its structure including the absolute configuration was established by asymmetric total synthesis involving such key steps as the asymmetric Diels-Alder reaction using an aminodiene and the construction of an isoquinuclidine ring and an indole skeleton.


Assuntos
Alcaloides Indólicos/isolamento & purificação , Voacanga/química , Alcaloides Indólicos/química , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular , Estereoisomerismo , Tabernaemontana/química
14.
Zhong Yao Cai ; 35(2): 226-9, 2012 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-22822667

RESUMO

OBJECTIVE: To study the alkaloids of Voacanga africana. METHODS: The alkaloids were isolated by normal phase silica gel and Sephadex LH-20 column chromatography. Their structures were elucidated by analysis of spectroscopic data. RESULTS: Eight alkaloids were isolated and their structures were elucidated as voacangine(1), voacangine hydroxyindolenine(2), 19R-epi-voacristine(3), epi-ibogaine(4), vobasine(5), 19-epi-heyneanine(6), vobtusine(7) and voacamine(8). CONCLUSION: Compounds 2-4 and 6 are isolated from this plant for the first time.


Assuntos
Alcaloides/química , Voacanga/química , Alcaloides/isolamento & purificação , Ibogaína/análogos & derivados , Ibogaína/química , Ibogaína/isolamento & purificação , Espectroscopia de Ressonância Magnética , Casca de Planta/química , Raízes de Plantas/química , Caules de Planta/química
15.
Pharm Biol ; 50(9): 1183-93, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22834977

RESUMO

CONTEXT: Herbal remedies have been employed for the treatment and management of various ailments since the beginning of human civilization. Voacanga is an extensive genus of the family Apocynaceae and consists of small trees inhabiting the tropical and subtropical regions of Africa. Voacanga plants have been used in the treatment of leprosy, diarrhea, and generalized edema, convulsions in children as well as to treat cases of orchitis, ectopic testes and gonorrhea. OBJECTIVES: The aim of this review is to present as much information as was established from the available scientific literature. The present review comprises the ethnopharmacological, phytochemical and therapeutic potential of the plant genus Voacanga. METHODS: The present review reports on 111 natural products as found in 44 references compiled from the major databases, viz., Chemical Abstracts, Science Direct, SciFinder, PubMed, Dr. Dukes Phytochemical and Ethnobotany, CIMER, and InteliHealth. RESULTS: An exhaustive survey of the literature revealed that indole alkaoids and steroids constitute the major classes of phytoconstituents of this genus. Pharmacological reports revealed that products derived from this genus have been used for the treatment of cancer, and for CNS, cardiotonic, antituberculosis, acetylcholinesterase (AChE), butyrylcholinesterase, antagonistic, anti-diarrheal activities.


Assuntos
Extratos Vegetais/química , Extratos Vegetais/farmacologia , Voacanga/química , África , Alcaloides/análise , Alcaloides/farmacologia , Alcaloides/uso terapêutico , Animais , Humanos , Medicina Tradicional Africana , Extratos Vegetais/uso terapêutico , Especificidade da Espécie , Voacanga/crescimento & desenvolvimento , Voacanga/metabolismo
16.
Asian Pac J Trop Med ; 4(10): 824-8, 2011 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22014741

RESUMO

OBJECTIVE: To determine the antibacterial, antifungal, antiprotozoal, cytotoxic, and phytochemical properties of ethanol extracts of leaves of Voacanga globosa (Blanco) Merr. (V. globosa). METHODS: The extracts were tested against bacteria and fungus through disc diffusion assay; against protozoa through growth curve determination, antiprotozoal and cytotoxicity assays. RESULTS: The extract revealed antibacterial activities, inhibiting the growth of Staphylococcus aureus, Bacillus cereus, Pseudomonas aeruginosa, Micrococcus luteus, and Salmonella typhimurium. Antifungal assay showed that it inhibited Candida albicans. The antiprotozoal assay against Trichomonas vaginalis and Entamoeba histolytica showed that V. globosa can inhibit the parasites, wherein the action can be comparable to metronidazole. With the in situ cell death detection kit, Trichomonas vaginalis and Entamoeba histolytica exposed to V. globosa leaf extract was observed to fluoresce simultaneously in red and yellow signals signifying apoptotic-like changes. Preliminary phytochemical screening revealed the chemical composition of plant extract containing alkaloids, saponins, 2-deoxysugars, and hydrolysable tannins. CONCLUSIONS: Thus, this study provides scientific evidence on the traditional use of V. globosa leaf extract in treating microbial diseases. Further, the leaf extract can possibly be used to produce alternative forms of antimicrobials.


Assuntos
Extratos Vegetais/farmacologia , Folhas de Planta/química , Voacanga/química , Animais , Bactérias/efeitos dos fármacos , Bioensaio/métodos , Fungos/efeitos dos fármacos , Humanos , Testes de Sensibilidade Microbiana , Parasitos/efeitos dos fármacos
17.
Eur J Med Chem ; 46(7): 3118-23, 2011 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-21546135

RESUMO

Globospiramine (1), a new spirobisindole alkaloid possessing an Aspidosperma-Aspidosperma skeleton, together with deoxyvobtusine (2), deoxyvobtusine lactone (3), vobtusine lactone (4) and lupeol (5), were isolated and identified from Voacanga globosa through a bioassay-guided purification. The gross structure and absolute stereochemistry of 1 were established by circular dichroism spectroscopy, HR-MS and unambiguous NMR spectroscopic experiments. In addition, a new biogenetic pathway for the formation of the spiro-Aspidosperma-Aspidosperma skeleton is proposed. Alkaloid 1 showed potent antituberculosis activity against Mycobacterium tuberculosis H(37)Rv as evidenced in microplate Alamar blue assay (MIC = 4 µg/mL) and low-oxygen recovery assay (LORA (MIC = 5.2 µg/mL). The bisindole alkaloids also exhibited promising activity against acetylcholinesterase and, especially butyrylcholinesterase, with deoxyvobtusine (2) (IC(50) = 6.2 µM) as the most strongly inhibiting compound. This study extends the variety of alkaloid structural platforms which exhibit antimycobacterial and anticholinesterase activity.


Assuntos
Alcaloides/farmacologia , Antituberculosos/farmacologia , Butirilcolinesterase/química , Inibidores da Colinesterase/farmacologia , Alcaloides Indólicos/farmacologia , Mycobacterium tuberculosis/efeitos dos fármacos , Compostos de Espiro/farmacologia , Voacanga/química , Acetilcolinesterase/química , Alcaloides/química , Alcaloides/isolamento & purificação , Animais , Antituberculosos/química , Antituberculosos/isolamento & purificação , Inibidores da Colinesterase/química , Inibidores da Colinesterase/isolamento & purificação , Electrophorus , Cavalos , Alcaloides Indólicos/química , Alcaloides Indólicos/isolamento & purificação , Testes de Sensibilidade Microbiana , Mycobacterium tuberculosis/enzimologia , Mycobacterium tuberculosis/crescimento & desenvolvimento , Oxazinas , Triterpenos Pentacíclicos/isolamento & purificação , Triterpenos Pentacíclicos/farmacologia , Extratos Vegetais/química , Folhas de Planta/química , Compostos de Espiro/química , Compostos de Espiro/isolamento & purificação , Relação Estrutura-Atividade , Xantenos
18.
Bioorg Med Chem Lett ; 21(7): 1962-4, 2011 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-21376588

RESUMO

Three indole alkaloids, voacamine (1), 3,6-oxidovoacangine (2), and a new alkaloid, 5-hydroxy-3,6-oxidovoacangine (3), isolated from Voacanga africana were found to exhibit potent cannabinoid CB1 receptor antagonistic activity. This is the first example of CB1 antagonists derived from natural alkaloids.


Assuntos
Descoberta de Drogas , Alcaloides Indólicos/farmacologia , Receptor CB1 de Canabinoide/antagonistas & inibidores , Alcaloides Indólicos/química , Estrutura Molecular , Extratos Vegetais/farmacologia , Espectrometria de Massas por Ionização por Electrospray , Voacanga/química
19.
Int J Antimicrob Agents ; 36(3): 275-9, 2010 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-20580535

RESUMO

New drugs are needed to help overcome the increasing problem of drug resistance in parasites that cause diseases such as malaria and trypanosomiasis. In this study, alkaloid compounds isolated from extracts of the plants Flindersia amboinensis, Stephania zippeliana and Voacanga papuana from Papua New Guinea and Flindersia acuminata from Australia were examined for their antiparasitic activity against Plasmodium falciparum strains and Trypanosoma brucei brucei as well as their cytotoxicity against the mammalian cell lines HEK 293 and HeLa. The most active compound, dimethylisoborreverine (DMIB), showed submicromolar activity, with 50% inhibitory concentration (IC(50)) values between 20 nM and 810 nM both against drug-sensitive and drug-resistant P. falciparum strains, along with moderate selectivity against T. b. brucei and mammalian cells. Stage specificity studies revealed that P. falciparum trophozoite-stage parasites were more susceptible to DMIB than ring- or schizont-stage parasites. DMIB-treated trophozoites showed changes in food vacuole morphology, with an apparent reduction in haemozoin formation that does not appear to be inhibited via the direct binding of haem. These findings suggest a potential for indole alkaloids from Flindersia spp. as new antiparasitic agents.


Assuntos
Alcaloides/farmacologia , Antiparasitários/farmacologia , Extratos Vegetais/farmacologia , Plasmodium falciparum/efeitos dos fármacos , Trypanosoma brucei brucei/efeitos dos fármacos , Alcaloides/isolamento & purificação , Alcaloides/toxicidade , Animais , Antiparasitários/isolamento & purificação , Antiparasitários/toxicidade , Austrália , Linhagem Celular , Células Epiteliais/efeitos dos fármacos , Humanos , Concentração Inibidora 50 , Papua Nova Guiné , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/toxicidade , Rutaceae/química , Stephania/química , Voacanga/química
20.
Yakugaku Zasshi ; 129(8): 975-82, 2009 Aug.
Artigo em Japonês | MEDLINE | ID: mdl-19652504

RESUMO

Voacanga africana (Apocynaceae) is a small tropical African tree. The root bark and seeds of this tree contain a number of alkaloids, including ibogaine (a hallucinogenic/aphrodisiac compound in bark), tabersonine (a major constituteent of seeds) and other voacanga alkaloids, traditionally used in Africa for religious purposes. Recently, some kinds of products containing this plant (root bark and seeds) have been distributed in the drug market in expectation of its hallucinogenic/aphrodisiac effects. There has been no report that has discussed quantitative analyses of these alkaloids in the products and their botanical origins. In this study, to investigate the trend of such a non-controlled psychotropic plant of abuse, a simultaneous analytical method was developed using LC/MS for the voacanga alkaloids including ibogaine and tabersonine in the commercial products of V. africana. Moreover, the botanical origins of these products were investigated by DNA analyses. As a result of the LC/MS analyses, the products were classified into two chemical types; an ibogaine-type and a tabersonine-type. The samples of the ibogaine-type contain ibogaine (0.05-0.6%) and other voacanga alkaloids; voacamine, voacamidine and voacangine, while those of the tabersonine-type mainly contain tabersonine (0.6-1.6%). The sequence analyses of chloroplast DNA, trnL-F region suggested that most of the products were derived from V. africana or closely related plants. They were classified into four genotypes based on nucleotide sequence of the trnL-F IGS region. The proposed methods of chemical and DNA analyses would be useful for investigating the trend in the distribution of the products of V. africana.


Assuntos
Alcaloides/análise , DNA de Plantas , Plantas Medicinais/química , Análise de Sequência de DNA , Voacanga/química , Alcaloides/isolamento & purificação , Cromatografia Líquida , Genótipo , Espectrometria de Massas , Voacanga/genética
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