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O gênero Tabernaemontana, pertencente à família Apocynaceae, é constituído de aproximadamente 110 espécies. Dentre estas, a espécie, em estudo, Tabernaemontana catharinensis é conhecida popularmente no Brasil, como “leiteiro de vaca”. Essa espécie é especialmente rica em alcaloides indólicos, que são substâncias que possuem potenciais biológicos promissores, como a ação anticolinesterásica e antioxidante. O objetivo foi isolar, purificar e identificar alcaloides indólicos das cascas da raizes de Tabernaemontana catharinensis. O material vegetal foi seco à temperatura ambiente, moído e submetido a extração metanólica e, posteriormente, particionado com diclorometano/água. O estudo fitoquímico foi realizado por cromatografia em coluna e cromatografia de camada delgada analítica. O estudo da espécie T.catharinensis levou a identificação de quatro alcaloides: coronaridina (1), 12-metoxi-Nb-metilvoachalotina (2), 5,6-dioxoibogamina (3) e 19-(S)-heyneanina (4). A determinação estrutural dos compostos foi feita utilizando Ressonância Magnética Nuclear uni e bidimensional. Os alcalóides (3) e (4) estão sendo relatados pela primeira vez na espécie.

Background: Breast cancer could be a serious global health concern causing the best mortality rate in females. Available synthetic medicine to treat breast cancer are marred by extreme toxicity problems and recommend some alternate route to handle the dreadful disease. The present study is an Insilco effort to identify the antitumor potential of Tabernaemontana divaricata plant metabolites.Materials and Methods: The structure of the Human estrogen Receptor (HER), a possible target of breast cancer was selected as target molecules, retrieved from the protein data Bank (PDB) and therefore the structures of alkaloids compounds are collected from PubChem database. Molecular docking and drug similarity studies were performed for these alkaloids compounds to assess and analyze the anti-breast cancer action.Results: The detailed interaction studies of a few alkaloids (Coronaridine, Voacangine, Voacristine, Catharanthine, and Ibogamine) suggest that the compound could serve as probable lead molecules in drug development. All these five compounds also exhibited the highest binding affinity with human ER more significant than 8.7 Kcal/mol which is more affinity as compared to that of standard drugs Tamoxifen.Conclusion: The results of this study is enforced to design novel anti-cancerous medicine within the coming future. The interaction studies of the standard drug with breast cancer markers serve as a tool to synthesize new compounds of desired effectiveness against the deadly disease.

Monoterpenoid indole alkaloids (MIAs) of the ibogan type, such as ibogaine, have shown promising antiaddictive effects against several drugs of abuse in humans and animal models of addiction. Unfortunately, international ibogaine demand has led to the overexploitation of natural populations of the African species Tabernanthe iboga (Apocynaceae), the main source of this alkaloid. Therefore, it is necessary to identify alternative ibogan type alkaloid-containing plant species, as well as to develop new sustainable production systems for said group of pharmaceutically important compounds. In this review, we focus on strategies for the in vitro production of the antiaddictive ibogan type MIAs coronaridine, ibogamine, voacangine, and ibogaine (collectively named “CIVI-complex”) from Apocynaceae species, with particular emphasis on the Tabernaemontana genus. Since plant tissue culture (PTC)-related information on the CIVI-complex is scarce, we also consider reports on the in vitro production of other ibogan type MIAs and where necessary, of compounds belonging to the aspidospermatan, corynanthean, and plumeran type. This review aims at giving an overview of potential strategies to produce antiaddictive ibogan type alkaloids from in vitro cultures of Apocynaceae species.

Coronaridine (1) was isolated from the CH2Cl2 root extract of Tabernaemontana ternifolia. The structure of 1 was established from 1D- and 2D-NMR and HR-ESIMS experiments, and by comparison with rep...

A new iboga-vobasine-type isomeric bisindole alkaloid named voacamine A (1), along with eight known compounds&mdash, voacangine (2), voacristine (3), coronaridine (4), tabernanthine (5), iboxygaine (6), voacamine (7), voacorine (8) and conoduramine (9)&mdash, 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 &mu, M drug concentrations. The IC50 values of the isolates are 2.49&ndash, 5.49 &micro, M for microfilariae and 3.45&ndash, 17.87 &micro, M 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&ndash, 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.

To determine whether (+)-catharanthine induces sedative- or anxiolytic/anxiogenic-like activity in male mice, proper animal paradigms were used. The results showed that (+)-catharanthine induces sedative-like activity in the 63–72 mg/Kg dose range in a flumazenil-insensitive manner, but neither this effect nor anxiolytic/anxiogenic-like activity was observed at lower doses. To determine the underlying molecular mechanism of the sedative-like activity, electrophysiological and radioligand binding experiments were performed with (+)-catharanthine and (±)-18-methoxycoronaridine [(±)-18-MC] on GABAA (GABAARs) and glycine receptors (GlyRs). Coronaridine congeners both activated and potentiated a variety of human (h) GABAARs, except hρ1. (+)-Catharanthine-induced potentiation followed this receptor selectivity (EC50's in μM): hα1β2 (4.6 ± 0.8) > hα2β2γ2 (12.6 ± 3.8) ~ hα1β2γ2 (14.4 ± 4.6) indicating that both α1 and α2 are equally important, whereas γ2 is not necessary. (+)-Catharanthine was >2-fold more potent and efficient than (±)-18-MC at hα1β2γ2. (+)-Catharanthine also potentiated, whereas (±)-18-MC inhibited, hα1 GlyRs with very low potency. Additional [3H]-flunitrazepam competition binding experiments using rat cerebellum membranes clearly demonstrated that these ligands do not bind to the benzodiazepine site. This is supported by the observed activity at hα1β2 (lacking the BDZ site) and similar effects between α1- and α2-containing GABAARs. Our study shows, for the first time, that (+)-catharanthine induced sedative-like effects in mice, and coronaridine congeners potentiated human α1β2γ2, α1β2, and hα2β2γ2, but not ρ1, GABAARs, both in a benzodiazepine-insensitive fashion, whereas only (+)-catharanthine slightly potentiated GlyRs.

Chemical investigation of root bark of Glycosmis pentaphylla and stem bark of Tabernaemontana coronaria led to the isolation of three carbazole alkaloids glycozoline, glycozolidine and methyl carbazole 3-carboxylate, two furoquinoline alkaloids skimmianine and dictamine, an acridone alkaloid arborinine, three monomeric indole alkaloids coronaridine, 10-methoxy coronaridine and tabernaemontanine, and two dimeric indole alkaloids voacamine and tabernaelegantine B. Their structures were established by detailed spectral analysis. Mutagenic and antimutagenic potential of methanol extract of both plant materials were evaluated by Ames test against known positive mutagens 2-aminofluorine, 4-nitro-O-phenylenediamine and sodium azide using Salmonella typhimurium TA 98 and TA 100 bacterial strains both in the presence and absence of S9. Both the extracts were non-mutagenic in nature. Both the extracts of G. pentaphylla and T. coronaria exhibited significant antimutagenic activity against NPD and sodium azide for S. typhimurium TA98 and TA100 strains. The results indicated that the extracts could counteract the mutagenicity induced by different genotoxic compounds.

Several species from the Apocynaceae family, such as Tabernanthe iboga, Voacanga africana, and many Tabernaemontana species, produce ibogan type alkaloids, some of which present antiaddictive properties. In this study, we used gas chromatography/mass spectrometry (GC/MS) to examine the efficiency of methanol, acetone, ethyl acetate, dichloromethane, chloroform, and hydrochloric acid in extracting the antiaddictive compounds coronaridine, ibogamine, voacangine, and ibogaine (altogether the CIVI-complex) from the root barks of Tabernaemontana alba and Tabernaemontana arborea. These Mexican species have recently shown great potential as alternative natural sources of the aforementioned substances. Methanol proved to be the most suitable solvent. Furthermore, the crude methanolic extracts could be engaged in a one-step demethoxycarbonylation process that converted coronaridine and voacangine directly into its non-carboxylic counterparts ibogamine and ibogaine, respectively, without the intermediacy of their carboxylic acids. The established protocol straightforwardly simplifies the alkaloid mixture from four to two majority compounds. In summary, our findings facilitate and improve both the qualitative and quantitative analysis of CIVI-complex-containing plant material, as well as outlining a viable method for the bulk production of these scientifically and pharmaceutically important substances from Mexican Tabernaemontana species.

Ibogaine and other ibogan type alkaloids present anti-addictive effects against several drugs of abuse and occur in different species of the Apocynaceae family. In this work, we used gas chromatography-mass spectrometry (GC/MS) and principal component analysis (PCA) in order to compare the alkaloid profiles of the root and stem barks of four Mexican Tabernaemontana species with the root bark of the entheogenic African shrub Tabernanthe iboga. PCA demonstrated that separation between species could be attributed to quantitative differences of the major alkaloids, coronaridine, ibogamine, voacangine, and ibogaine. While T. iboga mainly presented high concentrations of ibogaine, Tabernaemontana samples either showed a predominance of voacangine and ibogaine, or coronaridine and ibogamine, respectively. The results illustrate the phytochemical proximity between both genera and confirm previous suggestions that Mexican Tabernaemontana species are viable sources of anti-addictive compounds.

Two new monoterpene indole alkaloids, isoakuammiline (1) and 18-hydroxypseudovincadifformine (2), and five known alkaloids, coronaridine (3), heyneanine (4), 3,19-oxidocoronaridine (5), tabersonine, and strictosidine, were identified from the fruit of Tabernaemontana litoralis. The structures of the alkaloids were determined using NMR and MS data analyses. While 18-hydroxypseudovincadifformine (2) showed a new hydroxylation pattern, isoakuammiline (1) revealed a novel skeleton for monoterpene indole alkaloids. In spite of the isolation of stemmadenine from the fruit tissues in other Tabernaemontana species, this vital biosynthetic precursor of iboga, aspidosperma, and pseudoaspidosperma skeletons was not found in T. litoralis.

The primary aim of this study was to determine the anti-neuropathic activity of (±)-18-methoxycoronaridine [(±)-18-MC] and (+)-catharanthine in mice by using the oxaliplatin-induced neuropathic pain paradigm and cold plate test. The results showed that both coronaridine congeners induce anti-neuropathic pain activity at a dose of 72 mg/kg (per os), whereas a lower dose (36 mg/kg) of (+)-catharanthine decreased the progress of oxaliplatin-induced neuropathic pain. To determine the underlying molecular mechanism, electrophysiological recordings were performed on α9α10, α3β4, and α4β2 nAChRs as well as voltage-gated calcium (CaV2.2) channels modulated by G protein-coupled γ-aminobutyric acid type B receptors (GABABRs). The results showed that (±)-18-MC and (+)-catharanthine competitively inhibit α9α10 nAChRs with potencies higher than that at α3β4 and α4β2 nAChRs and directly block CaV2.2 channels without activating GABABRs. Considering the potency of the coronaridine congeners at Cav2.2 channels and α9α10 nAChRs, and the calculated brain concentration of (+)-catharanthine, it is plausible that the observed anti-neuropathic pain effects are mediated by peripheral and central mechanisms involving the inhibition of α9α10 nAChRs and/or CaV2.2 channels.

Active plant metabolites have been used as prototype drugs. In this context, Tabernaemontana catharinensis (Apocynaceae) has been highlighted because of the presence of active indole alkaloids. Thus, this study aims the bio-guided search of T. catharinensis cytotoxic alkaloids. The chemical composition was identified by high-resolution mass spectrometry, and fractionation was performed by open column and preparative thin-layer chromatography, from plant stems. The enriched fractions were tested in vitro in tumour cells A375 (melanoma cell line) and A549 (adenocarcinomic human alveolar basal epithelial cells), and non-tumour Vero cells (African green monkey kidney epithelial cells). The alkaloids identified as active were submitted to in silico toxicity prediction by ADME-Tox and OSIRIS programs and, also, to molecular docking, using topoisomerase I (PDB ID: 1SC7) by iGEMDOCK. As a result, six sub-fractions were obtained, which were identified as containing 16-epi-affinine, 12-methoxy-n-methyl-voachalotine, affinisine, voachalotine, coronaridine hydroxyindoline and ibogamine, respectively. The affinisine-containing sub-fraction showed selective toxicity against A375, with an IC50 of 11.73 µg mL−1, and no cytotoxicity against normal cells (Vero). From the in silico toxicity test results, all indole alkaloid compounds had a low toxicity risk. The molecular docking data provided structural models and binding affinities of the plant’s indole alkaloids and topoisomerase I. In summary, this bio-guided search revealed that the indole alkaloids from T. catharinensis display selective cytotoxicity in A375 tumour cells and toxicity in silico. Particularly, affinisine might be a chemotherapeutic for A375 melanoma cells.

Four alkaloids, voacangine (1), isovoacangine (2), coronaridine (3), and coronaridine hydroxyindolenine (4), were isolated from the MeOH extract of Tabernaemontana divaricata aerial parts by activity-guided fractionation for Wnt signal inhibitory activity. Compounds 1-4 exhibited TCF/β-catenin inhibitory activities with IC50 values of 11.5, 6.0, 5.8, and 7.3 μM, respectively. Of these, coronaridine (3) decreased β-catenin levels in SW480 colon cancer cells, while this decrease in β-catenin was not suppressed by a co-treatment with 3 and MG132, a proteasome inhibitor. These results suggested that the decrease observed in β-catenin levels by coronaridine (3) did not depend on a proteasomal degradation process. On the other hand, the treatment of SW480 cells with coronaridine (3) caused a decrease in β-catenin mRNA levels. Thus, coronaridine (3) may inhibit the Wnt signaling pathway by decreasing the mRNA expression of β-catenin.

To characterize the interaction of coronaridine congeners with human (h) α3β4 nicotinic acetylcholine receptors (AChRs), structural and functional approaches were used. The Ca(2+) influx results established that coronaridine congeners noncompetitively inhibit hα3β4 AChRs with the following potency (IC50's in μM) sequence: (-)-ibogamine (0.62±0.23)∼(+)-catharanthine (0.68±0.10)>(-)-ibogaine (0.95±0.10)>(±)-18-methoxycoronaridine [(±)-18-MC] (1.47±0.21)>(-)-voacangine (2.28±0.33)>(±)-18-methylaminocoronaridine (2.62±0.57 μM)∼(±)-18-hydroxycoronaridine (2.81±0.54)>(-)-noribogaine (6.82±0.78). A good linear correlation (r(2)=0.771) between the calculated IC50 values and their polar surface area was found, suggesting that this is an important structural feature for its activity. The radioligand competition results indicate that (±)-18-MC and (-)-ibogaine partially inhibit [(3)H]imipramine binding by an allosteric mechanism. Molecular docking, molecular dynamics, and in silico mutation results suggest that protonated (-)-18-MC binds to luminal [i.e., β4-Phe255 (phenylalanine/valine ring; position 13'), and α3-Leu250 and β4-Leu251 (leucine ring; position 9')], non-luminal, and intersubunit sites. The pharmacophore model suggests that nitrogens from the ibogamine core as well as methylamino, hydroxyl, and methoxyl moieties at position 18 form hydrogen bonds. Collectively our data indicate that coronaridine congeners inhibit hα3β4 AChRs by blocking the ion channel's lumen and probably by additional negative allosteric mechanisms by interacting with a series of non-luminal sites.

The inhibitory activity of coronaridine congeners on human (h) α4β2 and α7 nicotinic acetylcholine receptors (AChRs) is determined by Ca2+ influx assays, whereas their effects on neurons in the ventral inferior (VI) aspect of the mouse medial habenula (MHb) are determined by patch-clamp recordings. The Ca2+ influx results clearly establish that coronaridine congeners inhibit hα3β4 AChRs with higher selectivity compared to hα4β2 and hα7 subtypes, and with the following potency sequence, for hα4β2: (±)-18-methoxycoronaridine [(±)-18-MC] > (+)-catharanthine > (±)-18-methylaminocoronaridine [(±)-18-MAC] ∼ (±)-18-hydroxycoronaridine [(±)-18-HC]; and for hα7: (+)-catharanthine > (±)-18-MC > (±)-18-HC > (±)-18-MAC. Interestingly, the inhibitory potency of (+)-catharanthine (27 ± 4 μM) and (±)-18-MC (28 ± 6 μM) on MHb (VI) neurons was lower than that observed on hα3β4 AChRs, suggesting that these compounds inhibit a variety of endogenous α3β4* AChRs. In addition, the interaction of bupropion with (−)-ibogaine sites on hα3β4 AChRs is tested by [3H]ibogaine competition binding experiments. The results indicate that bupropion binds to ibogaine sites at desensitized hα3β4 AChRs with 2-fold higher affinity than at resting receptors, suggesting that these compounds share the same binding sites. In conclusion, coronaridine congeners inhibit hα3β4 AChRs with higher selectivity compared to other AChRs, by interacting with the bupropion (luminal) site. Coronaridine congeners also inhibit α3β4*AChRs expressed in MHb (VI) neurons, supporting the notion that these receptors are important endogenous targets for their anti-addictive activities.

Virtual Screening and Molecular Docking analysis for Tabernaemontana divaricata derived 66 Law Molecular Weight Compounds (LMW) was conducted and to identified and predicted novel molecules as a inhibitor of Streptococcus pneumonia. The investigation has revealed several compounds with optimum binding towards Penicillin-binding proteins, Sialidases, Aspartate betasemialdehide dehydrogenase cell membrane protein of Streptococcus pneumonia. Docking results were computed in term of binding energy, ligand efficiency and number of hydrogen bonding. Apparicine (-5.14), 5-Hydroxyvoaphylline (-4.78), Voacangine (-4.7), 19-Hydroxycoronaridine (-4.44) and Coronaridine (-4.72) are identified as most suitable to bind with N-acetylglucosamine-1- phosphate uridyltransferase receptor. Ervaticine (-6.33), Ibogamine (-6.15), Methylvoaphylline (-5.74) and Coronaridine hydroxyindolenine (-5.32) has showed novel binding against the penicillin-binding proteins. Ervaticine (-6.42), 5-oxo-11-hydroxy voaphylline (-6.18), Conolobine B (-6.02) has found optimum binding against the active site of NanB sialidase of Streptococcus pneumonia. The compounds 3S-Cyanocoronaridine (-6.71), 19-Epivoacristine (-5.48) and Ervaticine(-5.45) interacting with aspartate beta-semialdehide and found suitable with least docking score.

We report on the isolation and the identification of the alkaloid coronaridine from Vinca rosea L. The 1H NMR data are discussed.

The leaves of Voacanga foetida (Bl.) Rolfe, have been used ethnomedically for the treatment of wounds, itches, and swellings particularly in Lombok island. A phytochemical study has been done to investigate chemical compounds responsible against the cause of the diseases. By separating alkaloidal fraction from the leaves was found voacristine 1 as the major alkaloidal compound, and voacangine 2 and coronaridine 3 as the minor components. The structure elucidation of the compounds was carried out on the basis of spectroscopy data. A structure revision of voacristine 1 was also reported. Keywords: alkaloids, Voacanga foetida, Lombok

A necessidade da introdução de novos agentes quimioterápicos é uma realidade no controle de doenças infecciosas. O Brasil é o país mais rico em biodiversidade, e o Laboratório de Extração da Universidade Paulista tem coletado plantas na Amazônia e Mata Atlântica com a finalidade de identificar extratos vegetais antibacterianos e antitumorais. Estudos prévios demonstraram que a fração etanólica obtida do extrato bruto orgânico do caule de Tabernaemontana angulata Mart. ex Müll. Arg. apresentou atividade antimicrobiana significante contra Staphylococcus aureus ATCC6538, no ensaio de diluição em caldo. Verificou-se por cromatografia em camada delgada que os compostos majoritários presentes na fração ativa eram alcalóides. No presente trabalho, foi obtida a fração de alcalóides totais a partir do extrato bruto, da qual os compostos majoritários foram isolados por sucessivas cromatografias e, posteriormente, identificados por CG-EM e ¹H-RMN como os alcalóides indólicos coronaridina e voacangina. As frações obtidas do isolamento foram testadas no ensaio biológico, porém não demonstraram atividade antimicrobiana. Introducing new chemotherapeutic agents is a great demand in the control of infectious diseases. Brazil is one of the richest countries in biodiversity and the Laboratório de Extração at UNIP has been collecting plants from the Amazon and Atlantic Rain Forests with the aim of screening for new antibacterial and antitumor plant extracts. Previous studies demonstrated that the ethanol fraction obtained from the crude extract of Tabernaemontana angulata stems showed an antibacterial activity against Staphylococcus aureus (ATCC 6538) in the microdilution broth assay. Two alkaloids were the major compounds in the active fraction, verified by thin layer chromatography analysis. In the present study, the total alkaloids were obtained from the crude extract and were fractionated by preparative thin layer chromatography for the isolation of the main components. The isolated compounds were identified by GC/MS and ¹H-NMR as coronaridine and voacangine. The alkaloid fractions obtained from the isolation procedure were tested for antibacterial activity, but no activity was detected.

The alkaloids (-)-pseudotabersonine (I), (-)-pseudovincadifformine (II) and (+)-coronaridine (III) are synthesized from commercially available (+)-catharanthine by Ir-catalyzed photoredox reaction.

Indole alkaloids from Tabernaemontana catharinensis, collected from different places, were extracted using a mixture of supercritical CO2 plus ethanol. The effects of the process variables: temperature, pressure, solvent flow rate, and percentage of cosolvent on the total yield, chemical composition of the extract, and extraction kinetics were determined. The extracts were solvent-partitioned and their composition analyzed by TLC, GC-MS and 1H and 13C NMR. Voacangine and coronaridine were identified as the major compounds in the extracts; the individual alkaloids were quantified by GC-FID using external standard. At 250 bar and 45 °C the largest yield (1.29%) and the faster extraction rate were obtained; increasing the percentage of cosolvent improved the extraction rate as well as the yield. Employing an intermittent process consisting in six pressurization–depressurization steps appreciably reduced the total extraction time.

In previous studies, we demonstrated the leishmanicide effect of coronaridine, a natural indole alkaloid isolated from stem bark ofPeschiera australis(Delorenzi et al., Antimicrob. Agents Chemother.45:1349-1354, 2001). In this study we show the leishmanicidal effect of the synthetic coronaridine and its racemic 18-methoxylated analog, 18-methoxycoronaridine. Both alkaloids revealed a potent leishmanicide effect againstLeishmania amazonensis, a causative agent of cutaneous and diffuse cutaneous leishmaniasis in the New World. Despite their potent leishmanicide effect, both alkaloids were neither toxic to murine macrophages nor did they modulate their oxidative or cytokine production responses.

In this study, we show the leishmanicidal effects of a chloroform fraction (CLF) and a purified indole alkaloid obtained from crude stem extract ofPeschiera australisagainstLeishmania amazonensis, a causative agent of cutaneous leishmaniasis in the New World. In a bioassay-guided chemical fractionation, the leishmanicidal activity in CLF completely and irreversibly inhibited promastigote growth. This fraction was also active against amastigotes in infected murine macrophages. Chemical analysis of CLF identified an iboga-type indole alkaloid coronaridine as one of its major compounds. Coronaridine showed potent antileishmanial activity, inhibiting promastigote and amastigote growth. Promastigotes and amastigotes treated with CLF or coronaridine showed pronounced alterations in their mitochondria as assessed by transmission electron microscopy.

Condensation of indoloazepines bearing the chiral N b -substituents: 1-( R )-naphthyl-α-ethyl, [1-( R )-[( S )-2-(diphenylphospheno)ferrocenyl]-ethyl], or 2,3-( R )-ferroceno-6,6-dimethyl-1-( S )-cyclohexyl, with 4-(1,3-dioxolan-2-yl)-hexanal, or with 4-(1,3-dioxolan-2-yl)-6-methoxyhexanal, gave diastereoselectively, through a secodine-type intramolecular Diels–Alder reaction, tetracyclic intermediates that could be carried to (−)-coronaridine or to the important anti-addictive (−)-18-methoxycoronaridine. The 2,3-( R )-ferroceno-6,6-dimethyl-1-( S )-cyclohexyl chiral auxiliary was most effective, providing >99% ee of a tetracyclic intermediate after removal of the chiral auxiliary group.

Through bioassay-guided fractionation and chromatography technique, eight indole alkaloids were furnished from the stems of Ervatamia hainanensis. All isolates were evaluated for acetylcholinesterase (AChE) inhibition activities, in which compounds 1 and 3 exhibited the same level of activities as galantamine, a marketed cholinesterase inhibitor for the treatment of Alzheimer's disease. Discussion about the relationships between structure and activity of these alkaloids was also presented.

Six indole alkaloids were isolated from the stems of Ervatamia yunnanensis. Among them, yunnanensine (I) is new. The other five are known alkaloids, namely: 19,20-E-vallesamine (II), 19s-heyneanine (III), ibogaine (IV), ibogamine (V), coronaridine (VI). The structural elucidation of the alkaloids was based on spectral means.

This paper reports the separation and identification of indole alkaloids, steroids and triterpenoids from the ethanolic extracts of Tabernaemontana hilariana (Apocynaceae). The alkaloidal fractions from the ethanolic extracts obtained (root barks, green fruits, ripe fruits and seeds) were fractionated and analysed by thin-layer chromatography, capillary gas chromatography–flame ionization detection (cGC–FID) as well as by high-resolution gas chromatography–mass spectrometry (HRGC–MS). 3-Hydroxycoronaridine, ibogamine, coronaridine pseudoindoxyl, coronaridine, catharanthine, voacangine hydroxyindolenine, voacangine pseudoindoxyl, tabernanthine, tetraphyllicine, 3-hydroxyvoacangine, voacangine, isovoacangine and 3-oxocoronaridine were identified. The insoluble fraction of ethanolic extracts obtained from the root barks and green fruits were analysed and ten aliphatic constituents were also identified by cGC–FID and HRGC–MS.

A new bisindole alkaloid, 19,20-dihydroervahanine A was isolated from the stems of Ervatamia coronaria grown in Brazil, together with five known alkaloids: coronaridine, heyneanine, voacristine, voacamine, descarbomethoxyvoacamine and five phenolic acids: vanillic, gentisic, syringic, 4-hydroxybenzoic and salicylic acid. The aqueous and alcoholic extracts, when administered p.o. or i.p. to rats 1 h before subplantar injection of carrageenin had a significant anti-inflammatory effect. The alcoholic extract also had an analgesic effect and increased the pentobarbital induced sleeping time.

Chemical study of the leaves and stem bark of Ervatamia peduncularis afforded two novel bisindole alkaloids, pedunculine and peduncularidine, together with seven known alkaloids, coronaridine, coronaridine hydroxyindolenine, eglandine, heyneanine, eglandulosine, heyneanine hydroxyindolenine and N(1)-methyl-aspidos-permidine. Structural elucidation of the new alkaloids was based on their spectral data.

During an investigation of the stem bark and leaves of Peschiera buchtieni , 34 alkaloids were isolated. Eight new alkaloids were obtained from the stem bark, N -methyl-pericyclivine, 18,19( R )-dihydroxycoronaridine, chloromethylene affinisinium, demethylaccedinisine, 18-hydroxyaffinisine, buchtienine, 3-hydroxytetrahydroolivacine and demethylceridimine. The known alkaloids from the stem bark were coronaridine, voaphylline, coronaridine hydroxyindolenine, heyneanine, eglandine, eglandulosine, 19-epi-heyneanine, voachalotine, ochropamine, olivacine, ibogamine, affinisine, N -oxyaffinisine, vallesamine, ( E )-isositsirikine, voaphylline hydroxyindolenine, normacusine B, janetine, 3,14-dihydroolivacine, 3′( R / S )-hydroxy- N -demethyl-tabernamine, 4′,17β-dihydrotchibangensine, ceridimine and N -demethyltabernamine. Apodine, voacristine, voacristine hydroxyindolenine and olivacine were identified in leaves.

Ibogaine, a naturally occurring alkaloid, has been claimed to be effective in treating addiction to opioid and stimulant drugs and has been reported to decrease morphine and cocaine self-administration in rats. The present study sought to determine if other iboga alkaloids, as well as the chemically related harmala alkaloid harmaline, would also reduce the intravenous self-administration of morphine and cocaine in rats. Because both ibogaine and harmaline induce tremors, an effect that may be causally related to neurotoxicity in the cerebellar vermis, the temorigenic activities of the other iboga alkaloids were assessed. Lastly, in view of the involvement of the dopaminergic mesolimbic system in the actions of drugs of abuse, the effects of some of the iboga alkaloids on extracellular levels of dopamine and its metabolites in the nucleus accumbens and striatum were determined. All of the tested alkaloids (i.e., ibogaine, tabernanthine, R- and S-coronaridine, R- and S-ibogamine, desethylcoronaridine, and harmaline) dose-dependently (2.5–80 mg/kg) decreased morphine and cocaine intake in the hour after treatment; decreases in morphine and cocaine intake intake were also apparent the day after administration of some but not all of these alkaloids (i.e., ibogaine, tabernanthine, desethylcoronaridine, and the R-isomers of coronaridine and ibogamine). In some rats, there were persistent decreases in morphine or cocaine intake for several days after a single injection or after two or three weekly injections of one or another of these alkaloids; R-ibogamine produced such effects more consistently than any of the other alkaloids. At the doses used to assess effects on drug self-administration, ibogaine, tabernanthine, desethylcoronaridine and harmaline all induced tremors for at least 2–3 h; both enantiomers of both coronaridine and ibogamine induced very weak or no tremors. Using in vivo microdialysis, the effects of the R- and S-enantiomers of coronaridine and ibogamine on extracellular dopamine levels in the nucleus accumbens and striatum were compared. The R-enantiomers decreased dopamine levels in both brain regions whereas the S-enantiomers produced no significant changes in dopamine levels in either region. The results of this study indicate that the ‘anti-addictive’ and tremorigenic effects of the iboga alkaloids can be dissociated and that long-term effects of these alkaloids on drug self-administration appear to be related to initial decreases in dopaminergic activity in specific brain areas.

Two cell lines of Tabernaemontana divaricata derived from the same suspension culture were compared with respect to their biotransformation capacity. One is a high indole alkaloid-producing culture which accumulated mainly O-acetylvallesamine. The other cell line biosynthesizes terpenoid indole alkaloids in much lower amounts. Both cell lines were cultured in medium containing either conopharyngine, coronaridine, vobasine or tabersonine. Chemical breakdown was followed in fresh and used culture medium in the absence of cell culture. All the alkaloids investigated underwent chemical transformation. Most of the biotransformation products accumulated by the cultures have been reported to occur in intact plants. Since all the alkaloids added were transformed in the same way by both cultures, the two cell lines seem to have the same biotransformation potential.

Seven indole alkaloids (coronaridine, tabersonine, olivacine, coronaridine-hydroxyindolenine, catharinensine, decarbomethoxyvoacamine AND tabernamine) were isolated from Peschiera australis in Brazil. Four phenolic acids (vanillic acid, syringic acid, gentisic acid AND salicylic acid) were also found. Crude extracts of P. australis seeds AND leaves showed in vivo antineoplastic activity against two experimental tumor models: Ehrlich's carcinoma AND Sarcoma 180. Aqueous AND alcohol leaf extracts administered to rats 1 h before subplantar carrageenan injection had a significant dose-related anti-inflammatory effect. The same extracts also showed analgesic activity against acetic acid-induced abdominal writhing.

A new alkaloid designated as ervatine, in addition to seven known alkaloids, viz. tabersonine, coronaridine, heyneanine, voacristine, voacristine hydroxyindolenine, hydroxyibogamine, and coronaridine hydroxyindolenine, were isolated from the fruit of Tabernaemontana heyneana Wall. Characterisation and structure elucidation of these compounds was made on the basis of their spectral analyses. The ethanolic extract and isolated alkaloids heyneanine and voacristine prevented pregnancy when administered during the preimplantation period in Sprague-Dawley rats. These were, however, found to possess significant uterotrophic activity.

Condensation of indoloazepines bearing the chiral N b -substituents: 1-( R )-naphthyl-α-ethyl, [1-( R )-[( S )-2-(diphenylphospheno)ferrocenyl]-ethyl], or 2,3-( R )-ferroceno-6,6-dimethyl-1-( S )-cyclohexyl, with 4-(1,3-dioxolan-2-yl)-hexanal, or with 4-(1,3-dioxolan-2-yl)-6-methoxyhexanal, gave diastereoselectively, through a secodine-type intramolecular Diels–Alder reaction, tetracyclic intermediates that could be carried to (−)-coronaridine or to the important anti-addictive (−)-18-methoxycoronaridine. The 2,3-( R )-ferroceno-6,6-dimethyl-1-( S )-cyclohexyl chiral auxiliary was most effective, providing >99% ee of a tetracyclic intermediate after removal of the chiral auxiliary group.

Generation of the key tetracyclic intermediates 14a,b in six steps (42% overall) and subsequent short reduction, oxidation, and arylation sequences results in total syntheses of the title compounds 8, 9, 10, 11, 12, and 13

The analgesic components were isolated from a Bornean medicinal plant, Tabernaemontana pauciflora BLUME (syn. Ervatamia blumeana MARK gr.), and the major components were identified as coronaridine and 3-(2-oxo-propyl)coronaridine. Four minor components were estimated to be 5R- and 5S-(2-oxopropyl)coronaridine, 3-(2-oxopropyl)voacangine and 3, 3'-(oxopropyl)dicoronaridine, which might be produced during the isolaion process. Voacangine was also isolated as a major component of T. pandacaqui POIR. Coronaridine and voacangine exhibited significant analgesic and hypothermic effects in mice at a dose of 25 mg/kg, p.o., while 3-(2-oxopropyl)coronaridine was less effective. The former two compounds also revealed a surface anesthesia.

A new sarpagine-type alkaloid with N-oxide group, called ervahainanmine, and three known ones including coronaridine, 19(S)-heyneanineguan, and coronaridine hydroxyindolenineguan were isolated from the stems of Evratamia hainanensis. The structure was established by spectroscopic methods, especially 2D NMR techniques.

Six indole alkaloids were isolated from the stems of Ervatamia yunnanensis. Among them, yunnanensine (I) is new. The other five are known alkaloids, namely: 19,20-E-vallesamine (II), 19s-heyneanine (III), ibogaine (IV), ibogamine (V), coronaridine (VI). The structural elucidation of the alkaloids was based on spectral means.

A new monoterpenoid indole alkaloid, 15,20-dehydro-3α-(2-oxopropyl) coronaridine (1), along with sixteen analogues (2–17) were isolated from the leaves of Catharanthus roseus cultivated in Yunnan. The new alkaloid was elucidated on the basis of extensive spectroscopic analysis, and the known alkaloids were identified by comparison with the reported spectroscopic data. Among them, alkaloid 16 was isolated from Catharanthus for the first time.

A fast and efficient procedure was elaborated to identify the alkaloid constituents from Tabernaemontana hilariana (Apocynaceae). The strategy based on fractioning of the crude alkaloid fraction in small cartridges followed by thin-layer chromatography (TLC), capillary gas chromatography-flame ionization detection as well as high-resolution gas chromatography-mass spectrometry afforded voacangine, coronaridine, ibogamine pseudoindoxyl, voacangine hydroxyindolenine, 3-hydroxycoronaridine and 3-(2-oxopropyl)coronaridine.

Ten indole alkaloids from the chloroform extract of stalk of Tabernaemontana australis (Muell. Arg) Miers were tentatively identified by GC–MS, viz. , coronaridine ( 1 ), voacangine ( 2 ), voacangine hydroxyindolenine ( 3 ), rupicoline ( 4 ), ibogamine ( 5 ), ibogaine ( 6 ), ibogaline ( 7 ), desethyl-voacangine ( 8) , voachalotine ( 9 ), and affinisine ( 10 ). Of these, the first four were isolated by silica gel open column chromatography, identified by uni- and bidimensional NMR, IR, MS and showed anti-cholinesterasic activity at the same concentration as the reference compounds physostigmine and galanthamine (detection limit of 0.01 mM) by TLC assay using the modified Ellman’s method.

The Iboga alkaloid congener 18-methoxycoronaridine (18-MC) exhibits in vitro leishmanicidal and in vivo anti-addiction properties. In this paper, we describe that 18-MC inhibits HIV-1 infection in human peripheral blood mononuclear cells (PBMCs) and monocyte-derived macrophages. We found that 18-MC inhibits the replication of primary isolates of HIV-1 in a dose-dependent manner, regardless of the preferential chemokine receptor usage of the isolates, at non-cell-toxic concentrations. The antiretroviral activity of 18-MC resulted in EC (50) values of 22.5 +/- 4.7 microM and 23 +/- 4.5 microM for R5 and X4 isolates, respectively, in PBMCs, and a therapeutic index (TI) of 14.5. Similar findings were observed for inhibition of HIV-1 replication in macrophages: EC (50) equal to 12.8 +/- 5 microM and 9.5 +/- 3 microM for an R5 virus after 14 and 21 days of infection, respectively, with TI equal to 25.6 and 34.5. 18-MC moderately inhibits the HIV-1 enzyme reverse transcriptase (IC (50) = 69.4 microM), which at least partially explains its antiretroviral activity.

A series of indole alkaloids of the ibogan-type was assessed for their cytotoxic effects as well as their potential in reversing MDR in vincristine-resistant KB cells. Of a total of 25 compounds tested, 3(S)-cyanocoronaridine, 3(S)-cyanoisovoacangine, 3(S)-cyanovoacangine, and 10,11-demethoxychippiine were found to show appreciable cytotoxicity toward KB cells, while coronaridine, heyneanine, 19-epi-heyneanine, dippinine B, and dippinine C, were found to reverse MDR in vincristine-resistant KB cells.

Bioassay-directed fractionation of the alkaloid portion of a CH(2)Cl(2)-MeOH extract of Tabernaemontana calcarea resulted in the isolation of the three new cytotoxic indole alkaloids, 1-3, and the 12 known alkaloids voacangine (4), isovoacangine (5), coronaridine (6), 11-hydroxycoronaridine (7), voacristine (8), 19-epi-voacristine (9), isovoacristine (10), ibogamine (11), 10-methoxyibogamine (12), 11-methoxyibogamine (13), heyneanine (14), and 19-epi-heyneanine (15). The structures of the new compounds 1-3 were elucidated on the basis of extensive 1D and 2D NMR spectroscopic interpretation. All the compounds exhibited cytotoxic activity against the A2780 ovarian cancer cell line.

A new sarpagine-type alkaloid with N-oxide group, called ervahainanmine, and three known ones including coronaridine, 19(S)-heyneanineguan, and coronaridine hydroxyindolenineguan were isolated from the stems of Evratamia hainanensis. The structure was established by spectroscopic methods, especially 2D NMR techniques.

Made available in DSpace on 2022-04-28T19:54:52Z (GMT). No. of bitstreams: 0 Previous issue date: 1999-01-01 This paper reports the separation of the indole alkaloids from the benzene extract of the root barks of Tabernaemontana hilariana (Apocynaceae). The crude alkaloid fraction was fractionated by droplet counter-current chromatography using a low polarity mixture (hexane:ethyl acetate:ethanol:water). Nine indole alkaloids (3-hydroxycoronaridine, coronaridine, voacangine, 3-(2-oxopropyl) coronaridine, voacangine hydroxyindolenine, ibogamine, voacangine pseudoindoxyl, coronaridine pseudoindoxyl and tabernanthine) were identified using thin layer chromatography, gas chromatography coupled with mass spectrometry and nuclear magnetic resonance spectroscopy. Depto. de Química Organica Inst. de Quim. de Araraquara - Unesp, CP. 355, 14800-900 Araraquara-Sao Paulo Depto. de Química Organica Inst. de Quim. de Araraquara - Unesp, CP. 355, 14800-900 Araraquara-Sao Paulo

In the crystal structure of the racemic title compound, C22H29N2O3+·Cl−, both NH groups form N—H...Cl hydrogen bonds with the chloride counter-ion, forming translational chains along theaaxis.