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Kopsileuconines A-D (1-4), four monoterpenoid bisindole alkaloids with unprecedented skeletons, along with their biosynthetically related precursors (5-8) were isolated from the roots of Kopsia hainanensis. Compound 1 possessed an undescribed C-6-C-5' dimerization pattern of aspidofractinine-type alkaloids. Compounds 2-4 were rhazinilam-kopsine (2) and rhazinilam-aspidofractinine type (3 and 4) bisindole alkaloids with undescribed skeletons, respectively. Their structures with absolute configurations were fully accomplished by extensive spectroscopic analysis, quantum-chemical calculations, and X-ray crystallography. A plausible biosynthetic pathway for 1-4 was proposed. Compound 2 exhibited a significant inhibitory effect against human lung cancer cell lines PC9 (EGFR mutant), with an IC50 value of 15.07 ± 1.19 µM.
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Phytochemical investigation on the extract of the seeds of Thevetia peruviana resulted in the isolation of six new cardiac glycosides, namely theveperosides A-F (1-6), including a rare 19-nor-cardenolide (1), together with seven known analogues (7-13). The chemical structures of these compounds were determined based on detailed spectroscopic analysis. The cytotoxic activities of 1-13 were evaluated against MCF-7, HCT-116, HeLa, and HepG2 cancer cell lines, and their structure-activity relationships (SARs) were investigated. Compound 3 exhibited the significant cytotoxic effects with IC50 values ranging from 0.032 to 0.055 µΜ, which could induce HepG2 cells apoptosis in a dose-dependent manner.
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Antineoplásicos Fitogénicos , Glicósidos Cardíacos , Fitoquímicos , Semillas , Thevetia , Humanos , Glicósidos Cardíacos/farmacología , Glicósidos Cardíacos/aislamiento & purificación , Glicósidos Cardíacos/química , Semillas/química , Estructura Molecular , Antineoplásicos Fitogénicos/farmacología , Antineoplásicos Fitogénicos/aislamiento & purificación , Thevetia/química , Relación Estructura-Actividad , Fitoquímicos/farmacología , Fitoquímicos/aislamiento & purificación , Apoptosis/efectos de los fármacosRESUMEN
Eleven undescribed monoterpenoid bisindole alkaloids, alstomaphyines A-K (1-11), along with three known analogues were isolated from the leaves and stem bark of the Alstonia macrophylla. Compounds 1-3 were unprecedented dimerization alkaloids incorporating a macroline-type motif with an ajmaline-type motif via a C-C linkage. Their structures and absolute configurations were elucidated by extensive spectroscopic analysis, electronic circular dichroism (ECD) calculation, and CD exciton chirality method. Compounds 1-3 displayed potential inhibitory bioactivity against AChE with IC50 values of 4.44 ± 0.35, 3.59 ± 0.18, and 3.71 ± 0.23 µM, respectively. Enzyme kinetic study revealed compounds 1-3 as mixed competitive AChE inhibitors. Besides, compounds 8 and 12-14 exhibited better cytotoxicity against human cancer cell line HT-29 than cisplatin. Flow cytometry data revealed that compounds 8, 13, and 14 significantly induced the HT-29 cells arrest in G0/G1 phase in a concentration-dependent manner.
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Aqueous and hydroalcoholic extracts from the pulp of Ambelania acida Aubl. (Apocynaceae) fruits were subjected to analysis through UHPLC-HRMS and antioxidant potential using the TPC, DPPH, ABTS, FRAP, and ORAC assays. A putative identification of the compounds carried out by comparison of the fragmentation spectra revealed the predominance of the monoterpene indole alkaloids tabersonine, pseudocopsinine, ajmalicine, and strictosidine. Additionally, gallic acid, caffeic acid, citric acid, 3-O-p-coumaroylquinic acid, chlorogenic acid, catechin, ellagic acid, eschweilenol C (ellagic acid deoxyhexoside), and sucrose were identified. In face of the phenolic compounds observed, hydroalcoholic extract showed a higher antioxidant activity compared to the aqueous extract, observed at TPC (108.85 mg GAE/100g), FRAP (0.73 µmol Fe2SO4/g), DPPH (1221.76 µmol TE/g), ABTS (3460.00 µmol TE/g), and ORAC assays (120.47 µmol TE/g). These findings underscore the abundant presence of bioactive compounds, including phenolics and alkaloids, in an edible Amazonian fruit.
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Six undescribed bisindole alkaloids, namely taberdisines A-F (1-6), were isolated from the leaves of Tabernaemontana divaricata 'Dwaft'. Among them, alkaloids 1 and 2 were the first examples of strychnos-iboga type alkaloid with both C-C linkage patterns. Alkaloid 3, a new type of aspidosperma-iboga with a furan-ring, as well as other three undescribed ones was disclosed. Their structures were elucidated by comprehensive spectroscopic analyses. Alkaloids 1 and 5 showed insecticide activity on Sf9 cell and eggs of Spodoptera frugiperda in vivo, which might explain the potential of the plants for insect resistance.
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Alcaloides Indólicos , Insecticidas , Hojas de la Planta , Spodoptera , Tabernaemontana , Tabernaemontana/química , Hojas de la Planta/química , Insecticidas/química , Insecticidas/farmacología , Insecticidas/aislamiento & purificación , Animales , Spodoptera/efectos de los fármacos , Alcaloides Indólicos/química , Alcaloides Indólicos/aislamiento & purificación , Alcaloides Indólicos/farmacología , Estructura Molecular , Células Sf9RESUMEN
Specialized metabolites possess diverse interesting biological activities and some cardenolides- and monoterpene indole alkaloids- (MIAs) derived pharmaceuticals are currently used to treat human diseases such as cancers or hypertension. While these two families of biocompounds are produced by specific subfamilies of Apocynaceae, one member of this medicinal plant family, the succulent tree Pachypodium lamerei Drake (also known as Madagascar palm), does not produce such specialized metabolites. To explore the evolutionary paths that have led to the emergence and loss of cardenolide and MIA biosynthesis in Apocynaceae, we sequenced and assembled the P. lamerei genome by combining Oxford Nanopore Technologies long-reads and Illumina short-reads. Phylogenomics revealed that, among the Apocynaceae whose genomes have been sequenced, the Madagascar palm is so far the species closest to the common ancestor between MIA producers/non-MIA producers. Transposable elements, constituting 72.48% of the genome, emerge as potential key players in shaping genomic architecture and influencing specialized metabolic pathways. The absence of crucial MIA biosynthetic genes such as strictosidine synthase in P. lamerei and non-Rauvolfioideae species hints at a transposon-mediated mechanism behind gene loss. Phylogenetic analysis not only showcases the evolutionary divergence of specialized metabolite biosynthesis within Apocynaceae but also underscores the role of transposable elements in this intricate process. Moreover, we shed light on the low conservation of enzymes involved in the final stages of MIA biosynthesis in the distinct MIA-producing plant families, inferring independent gains of these specialized enzymes along the evolution of these medicinal plant clades. Overall, this study marks a leap forward in understanding the genomic dynamics underpinning the evolution of specialized metabolites biosynthesis in the Apocynaceae family, with transposons emerging as potential architects of genomics restructuring and gene loss.
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The genus Vincetoxicum includes a couple of highly invasive vines in North America that threaten biodiversity and challenge land management strategies. Vincetoxicum species are known to produce bioactive phenanthroindolizidine alkaloids that might play a role in the invasiveness of these plants via chemical interactions with other organisms. Untargeted, high-resolution mass spectrometry-based metabolomics approaches were used to explore specialized metabolism in Vincetoxicum plants collected from invaded sites in Ontario, Canada. All metabolites corresponding to alkaloids in lab and field samples of V. rossicum and V. nigrum were identified, which collectively contained 25 different alkaloidal features. The biosynthesis of these alkaloids was investigated by the incorporation of the stable isotope-labelled phenylalanine precursor providing a basis for an updated biosynthetic pathway accounting for the rapid generation of chemical diversity in invasive Vincetoxicum. Aqueous extracts of aerial Vincetoxicum rossicum foliage had phytotoxic activity against seedlings of several species, resulting in identification of tylophorine as a phytotoxin; tylophorine and 14 other alkaloids from Vincetoxicum accumulated in soils associated with full-sun and a high-density of V. rossicum. Using desorption-electrospray ionization mass spectrometry, 15 alkaloids were found to accumulate at wounded sites of V. rossicum leaves, a chemical cocktail that would be encountered by feeding herbivores. Understanding the specialized metabolism of V. rossicum provides insight into the roles and influences of phenanthroindolizidine alkaloids in ecological systems and enables potential, natural product-based approaches for the control of invasive Vincetoxicum and other weedy species.
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Alcaloides , Indolizinas , Fenantrenos , Vincetoxicum , Espectrometría de MasasRESUMEN
Rauvolfia mannii is a plant from western and eastern areas of African continent and is widely used in folk medicine for the treatment of various diseases including malaria. Herein, one previously undescribed acylated triterpene (1), together with five already published natural products (2-6) were removed from its roots. The chemical structures of these compounds were determined by spectroscopic and spectrometric means (NMR, HRESIMS, IR and UV). In addition to the isolated triterpenoids, components 5 and 6 are also newly reported from the genus Rauvolfia. Moreover, some constituents were further tested against the chloroquine-sensitive strain of P. falciparum (3D7). It has been found that 3 and 4 showed a moderate antiplasmodial activity with IC50 values of 46.25 and 39.79 µM respectively.
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In tropical forests, Hoya, a plant with significant indigenous medicinal applications, has been underexplored in pharmacological studies. This systematic review meticulously investigates the diverse pharmacological effects exhibited by various Hoya species on human health. A comprehensive literature search, encompassing Scopus, ScienceDirect, and SpringerLink databases, employed specific keyword combinations ('Hoya' and 'pharmacological properties' OR 'pharmacology property'). The included studies exclusively focused on Hoya's impact on human health. The findings underscore Hoya's potential as a medicinal plant, demonstrating promising attributes such as anticancer, antibacterial, antioxidant, anti-inflammatory, anti-diabetic, antinociceptive, and parasympatholytic effects. Despite these promising indications, the review underscores the necessity for further in vivo investigations to fully unlock Hoya's therapeutic potential. A comprehensive understanding of its mechanisms of action, efficacy, and safety in living systems is imperative for realising its holistic therapeutic benefits.
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Phytochemical investigation of the roots of Zygostelma benthamii Baill. (Apocynaceae) led to the isolation of eleven known compounds. The isolated compounds were identified by analysis of physical and spectroscopic data. We report three phenolic compounds (1-3), four triterpenoids (4-7), one coumarin (8), one lignan (9), one pregnane terpenoid (10), and one diterpenoid (11). It is the first time that Zygostelma benthamii is investigated, and this is therefore the first study of the Zygostelma genus. In addition, compound 7 and 11 are reported from the Apocynaceae family for the first time. Compounds 6, 7, 10 and 11 were evaluated against several cancer cell lines (KKU-M213B, KKU-100, KKU-M055, and A549) and Vero cells. Compound 10 showed strong anti-proliferative activity against all the selected cell lines, with IC50 values in the range of 1.70-6.8 µg/mL.
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ETHNOPHARMACOLOGICAL RELEVANCE: Melodinus axillaris W.T.Wang has been widely used as an important medicine in China. In the folk of China, its whole plant has been used for fractures, rheumatic heart disease, testitis, hernia, abdominal pain, and dyspepsia, etc. Despite its extensive use, there is a shortage of literature investigating the specific bioactive compounds and underlying mechanisms responsible for their anti-inflammatory effects. This knowledge gap serves as the primary impetus for conducting this study, which aims to shed light on the previously unexplored therapeutic potential of M. axillaris. AIM OF THE STUDY: This study aims to investigate the material basis and potential mechanism of anti-inflammatory activity of M. axillaris. MATERIALS AND METHODS: Compounds were isolated from the 95% ethanol extract of M. axillaris using a systematic phytochemical method. The structures were established by extensive spectroscopic analysis, including 1D and 2D NMR, HR-ESI-MS, ECD calculation, and DP4+ analysis. The anti-inflammatory activities of ethanol extract and compounds from M. axillaris were tested by an inflammation model of LPS-stimulated RAW264.7 cells in vitro. Western blot analysis was employed to evaluate the expressions of COX-2, iNOS, and NF-κB signaling pathways, aiming to elucidate the underlying mechanisms. RESULTS: Eleven undescribed monoterpenoid indole alkaloids (MIAs), axillines A-K (1-11), along with thirteen known analogs were isolated from M. axillaris. Compound 1 was the first representative of vincadine alkaloid with unprecedented 6/5/9/6/6 skeletons. Compounds 1-11 and ethanol extract showed significant anti-inflammatory effects in vitro. Among them, compound 2 had the best activity of inhibiting NO release (IC50 = 3.7 ± 0.9 µM). Additionally, subsequent Western blot analysis revealed that 2 could significantly inhibit the up-regulation of NF-κB signaling pathways, iNOS, and COX-2 in LPS-stimulated RAW264.7 cells, thereby demonstrating its anti-inflammatory activity. CONCLUSION: This study provides support for the traditional use of M. axillaris in terms of its anti-inflammatory properties and highlights the potential of MIAs as promising candidates for further development as anti-inflammatory drugs.
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FN-kappa B , Alcaloides de Triptamina Secologanina , Ratones , Animales , FN-kappa B/metabolismo , Alcaloides de Triptamina Secologanina/farmacología , Ciclooxigenasa 2/metabolismo , Lipopolisacáridos/farmacología , Transducción de Señal , Antiinflamatorios/farmacología , Células RAW 264.7 , Extractos Vegetales/farmacología , Etanol/farmacologíaRESUMEN
Three previously undescribed compounds named rauvolphyllas A-C (1-3), along with thirteen known compounds, 18ß-hydroxy-3-epi-α-yohimbine (4), yohimbine (5), α-yohimbine (6), 17-epi-α-yohimbine (7), (E)-vallesiachotamine (8), (Z)-vallesiachotamine (9), 16S-E-isositsirikine (10), Nb -methylisoajimaline (11), Nb -methylajimaline (12), ajimaline (13), (+)-lyoniresinol 3α-O-ß-D-glucopyranoside (14), (+)-isolarisiresinol 3α-O-ß-D-glucopyranoside (15), and (-)-lyoniresinol 3α-O-ß-D-glucopyranoside (16) were isolated from the aerial parts of Rauvolfia tetraphylla L. Their chemical structures were elucidated based on the extensive spectroscopic interpretation of HR-ESI-MS, 1D and 2D NMR spectra. The absolute configurations of 2 and 3 were determined by experimental ECD spectra. Compounds 5, 6, 7, and 11-13 exhibited nitric oxide production inhibition activity in LPS-activated RAW 264.7 cells with the IC50 values of 79.10, 44.34, 51.28, 33.54, 37.67, and 28.56â µM, respectively, compared to that of the positive control, dexamethasone, which showed IC50 value of 13.66â µM. The other isolates were inactive with IC50 values over 100â µM.
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Alcaloides , Anisoles , Lignanos , Naftalenos , Rauwolfia , Animales , Ratones , Lignanos/química , Células RAW 264.7 , Lipopolisacáridos/farmacología , Óxido Nítrico , Alcaloides/análisis , Espectroscopía de Resonancia Magnética , Componentes Aéreos de las Plantas/química , Yohimbina , Estructura MolecularRESUMEN
Nine previously unreported various types of monoterpenoid indole alkaloids, together with seven known analogues were isolated from the stem barks of Alstonia scholaris through a silica gel free methodology. The structures of 1-9 were elucidated by spectroscopic data analysis, electronic circular dichroism calculations, and single-crystal X-ray diffraction. Compound 1 is a modified echitamine-type alkaloid with a novel 6/5/5/7/6/6 hetero hexacyclic bridged ring system, and 8 and 9 exist as a zwitterion and trifluoroacetate salt, respectively. The anti-Toxoplasma activity of all isolates on infected Vero cells were evaluated, which revealed that compound 14 at 0.24 µM displayed potent activity. This study expanded the structural diversity of alkaloids of A. scholaris, and presented their potential application in anti-Toxoplasma drug development.
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Alstonia , Alcaloides de Triptamina Secologanina , Toxoplasma , Animales , Chlorocebus aethiops , Alcaloides de Triptamina Secologanina/farmacología , Alcaloides de Triptamina Secologanina/química , Estructura Molecular , Alstonia/química , Células Vero , Alcaloides IndólicosRESUMEN
Specialization in plant pollination systems can arise from traits that function as filters of flower visitors. This may involve chemical traits such as floral volatiles that selectively attract favoured visitors and non-volatile nectar constituents that selectively deter disfavoured visitors through taste or longer-term toxic effects or both. We explored the functions of floral chemical traits in the African milkweed Gomphocarpus physocarpus, which is pollinated almost exclusively by vespid wasps, despite having nectar that is highly accessible to other insects such as honeybees. We demonstrated that the nectar of wasp-pollinated G. physocarpus contains cardenolides that had greater toxic effects on Apis mellifera honeybees than on Vespula germanica wasps, and also reduced feeding rates by honeybees. Behavioural experiments using natural compositions of nectar compounds showed that these interactions are mediated by non-volatile nectar chemistry. We also identified volatile compounds with acetic acid as a main component in the floral scent of G. physocarpus that elicited electrophysiological responses in wasp antennae. Mixtures of these compounds were behaviourally effective for attraction of V. germanica wasps. The results show the importance of both volatile and non-volatile chemical traits as filters that lead to specialization in plant pollination systems.
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Néctar de las Plantas , Avispas , Animales , Abejas , Polinización , Flores , CardenólidosRESUMEN
BACKGROUND: Plant mitochondrial genomes are characterized by high homologous recombination, extensive intergenic spacers, conservation in DNA sequences, and gene content. The Hancornia genus belongs to the Apocynaceae family, with H. speciosa Gomes being the sole species in the genus. It is an siganificant commercial fruit crop; however, only a number of studies have been conducted. In this study, we present the mitochondrial genome of H. speciosa and compare it with other mitochondrial genomes within the Apocynaceae family. METHODS AND RESULTS: A total of 2.8 Gb of Illumina paired-end reads were used to obtain the mitogenome, resulting in 22 contigs that were merged using 6.1 Gb of Illumina mate-pair reads to obtain a circular chromosome. The mitochondrial genome of H. speciosa is circular, containing 63 predicted functional genes, spanning a length of 741,811 bp, with a CG content of 44%. Within the mitogenome, 50 chloroplast DNA sequences, equivalent to 1.72% of the genome, were detected. However, intergenic spaces accounted for 703,139 bp (94.79% of the genome), and 287 genes were predicted, totaling 173,721 bp. CONCLUSION: This suggests the incorporation of nuclear DNA into the mitogenome of H. speciosa and self duplication. Comparative analysis among the mitogenomes in the Apocynaceae family revealed a diversity in the structure mediated by recombination, with similar gene content and large intergenic spaces.
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Apocynaceae , Genoma Mitocondrial , Genoma Mitocondrial/genética , Retroelementos/genética , ADN Intergénico/genética , CloroplastosRESUMEN
Rauvolfia dichotoma, a shrub of Apocynaceae, was collected from the Islands of SAO Tome and Principe and cultivated locally for medicinal purpose. Phytochemical investigation of 95% ethanol extract from the stems and leaves of R. dichotoma led to the isolation of two new Nb-oxide indole alkaloids, namely Nb-oxide-mitoridine (1) and Nb-oxide-raucaffricine (2), together with two known alkaloids (3-4) and eleven known lignans (5-15). Their chemical structures were elucidated by extensive NMR and HR-ESI-MS data analysis. All compounds (except 13) were tested for their ß-hematin inhibitory activity. Compounds 2, 4, 14, and 15 showed certain inhibitory activity, indicating that they may have an antimalarial effect.
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Chemical investigation of Caralluma hexagona Lavranos, a wild plant growing in Yemen, led to the isolation of four previously undescribed acylated pregnane glycosides, hexagonosides A-D (1-4), together with two sets of mixtures (hexagonosides E and F), each set consists of three interconvertible pregnane glycoside isomers, hexagonosides E (5a-c) and F (6a-c). The chemical structures of the isolated pregnane glycosides were elucidated by extensive 1D/2D NMR and HRESI-MS analysis, featuring 6'-O-benzoyl-1'-O-ß-glucosyl residue at aglycone C-20; while aglycone C-3 was substituted with disaccharide sugar chain (1, 2, 5a-c) or a trisaccharide sugar chain (3, 4, 6a-c). Metabolites E and F included an extra benzoyl substitution in C-20 glucosyl residue which is migrating between the OH groups of C-2', C-3' and C-4' resulting in equilibrating conformations (5a-c and 6a-c) when incubated in HPLC solvent, which we confirmed by the analytical study.
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Apocynaceae , Glicósidos , Glicósidos/química , Pregnanos/química , Apocynaceae/química , Azúcares , Estructura MolecularRESUMEN
Six previously undescribed rigidly monoterpenoid indole alkaloids, alstolactines F-K (1-6), were isolated from Alstonia scholaris. Among them, a pair of cage-like epimers, 1 and 2, featuring a rare 6/5/6/6/7 ring system, represent the first example of C5âC20-olide, while compound 3 possesses unique degraded C18 and C19. The structures of the isolates were established by multiple spectroscopic analyses, quantum computational chemistry methods, and X-ray diffraction. Furthermore, the expression levels of proteins including NLRP3, TLR4, P-p65, NF-ĸB, Notch-2, IL-18, P-p38, and p38 in LPS-induced human normal hepatocyte (LO2) cells could be significantly downregulated by compounds 1-6, which showed potent anti-inflammatory bioactivity.
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Alstonia , Alcaloides de Triptamina Secologanina , Humanos , Alstonia/química , Lactonas , Alcaloides de Triptamina Secologanina/química , Indoles , Hepatocitos , Alcaloides Indólicos , Estructura MolecularRESUMEN
Plants of Asclepiadaceae and Apocynaceae family are a rich source of pregnane and pregnane glycosides. They are found in nature either in free state or as their glycosides. They have shown antitumor, anticancer, and hypoglycaemic, antioxidant and antimicrobial activities. In our continued studies on the isolation of pregnane glycosides we have isolated a novel pregnane pentaglycoside comprised of 2-deoxy and 2, 6-dideoxy monosaccharides from Wattakaka lanceolata (Asclepiadaceae). The structure of the new glycoside, Geneoside was established as11α, 12ß-O-diacetyl-drevogenin-P-3-O-ß-D-cymaropyaranosyl (1â4)-ß-D-cymaropyranosyl (1â4) -ß-D-Oleandropyranosyl (1â4)-ß-D-digitalopyranosyl (1â4)-ß-D-digitalopyranoside. The stereoscopic structure was established by chemical degradation, chemical transformation and recent physicochemical techniques viz 1H,13C, 2-D NMR (COSY, TOCSY, HSQC and HMBC) and Mass spectrometry.
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Phytochemical investigation of the two Tabernaemontana species (Apocynaceae) T. peduncularis Wall. and T. divaricata (L.) R.Br. ex Roem. & Schult. indicated closely related biosynthetic pathways leading to lipophilic and hydrophilic alkaloids. In total, 18 specialized metabolites comprising indole-derived alkaloid aglycones, three oxindole-derived alkaloid glycosides, and two iridoid glucosides could be identified in the studied species. Among the alkaloids, the two Iboga-type alkaloids 3,7-coronaridine isoindolenine, coronaridine 3,4-iminium and a javaniside derivative bearing a glucuronic acid, named javanuronic acid, could be described by spectroscopic and spectrometric methods for the first time. A docking experiment using alpha-fold was performed to generate a protein model of the enzyme 7-deoxyloganetic acid glucosyl transferase. Performed bioassays exhibited a growth reduction of neonate Spodoptera littoralis larvae and reduced cell viability of HepG2 cells of the extracts containing Iboga alkaloids, whilst the javaniside derivatives containing hydrophilic fraction did not show any effects. These findings indicate a high flexibility in the formation of bioactive indole alkaloid aglycones by Tabernaemontana species and also evidence similar accumulation trends in both species as well as indicate that biosynthetic routes leading to oxindole alkaloids like javanisides are more widespread than reported. Furthermore, the incorporation of the three novel compounds into potential biosynthetic pathways is discussed.