RESUMEN
Phytochemical investigation of the endophytic fungus Microdiplodia sp. afforded a new m-anisaldehyde derivative named microdiplanol (1) and a new 24-methylcholestanol derivative named microdiplane (2). Their structures were confirmed by a comprehensive analysis of 1D and 2D NMR and mass spectrometric data.
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Ascomicetos/química , Benzaldehídos/aislamiento & purificación , Colestanoles/aislamiento & purificación , Benzaldehídos/química , Colestanoles/química , Estructura Molecular , Resonancia Magnética Nuclear Biomolecular , EspañaRESUMEN
Besides plants and animals, the fungal kingdom consists of several species characterized by various forms and applications. Fungi are amazing producers of bioactive natural products with applications in medicine and agriculture. Though this kingdom has been extensively investigated worldwide, it remains relatively underexplored in Africa. To address the knowledge gaps, encourage research interest, and suggest opportunities for the discovery of more bioactive substances from African fungi, we considered it appropriate to extensively review the research work carried out on African fungi since 1988. This review summarizes the diversity and distribution of fungi throughout Africa, the secondary metabolites yet reported from studied fungi, their biological activities and, the countries where they were collected. The studied fungi originated from eleven African countries and were mainly endophytic fungi and higher fungi (macrofungi). Their investigation led to the isolation of five hundred and three (503) compounds with polyketides representing the main class of secondary metabolites. The compounds exhibited varied biological activities with antibacterial and antiproliferative properties being the most prominent.
RESUMEN
Canthium Lam. is a genus of flowering plants of the Rubiaceae family with about 80-102 species mainly distributed in Asia, tropical and subtropical Africa. The genus is closely related to Keetia E. Phillips and Psydrax Gaertn. and plants of this genus are used in folk medicine for the treatment of diarrhea, worms, leucorrhoea, constipation, snake bites, diabetes, hypertension, venereal diseases, and malaria. The present review covers a period of 52 years of biological and chemical investigations into the genus Canthium and has resulted in the isolation of about 96 secondary metabolites and several reported biological properties. For the Rubiaceae family, iridoids were reported as being the chemotaxonomic markers of this genus (â¼25%). Other reported classes of compounds include alkaloids, flavonoids, phenolic compounds, cyanogenic glycosides, coumarins, sugar alcohols, lignans, triterpenoids, and benzoquinones. The main reported pharmacological properties of most species of this genus include antioxidant, antiplasmodial, antipyretic, anti-inflammatory, antidiabetic, neuroprotective and antimicrobial activities with the latter being the most prominent. Considering the diversity of compounds reported from plants of this genus and their wide range of biological activities, it is considered to be worthy to further investigate them for the discovery of potentially new and cost effective drugs.
Asunto(s)
Fitoterapia , Rubiaceae , Etnofarmacología , Extractos Vegetales/química , Estructura Molecular , FitoquímicosRESUMEN
Chemical investigation of an endophytic fungus herein identified as Diaporthe cf. ueckeri yielded four known compounds, named cytochalasins H and J and dicerandrols A and B. Reports of acid sensitivity within the cytochalasan family inspired an attempt of acid-mediated conversion of cytochalasins H and J, resulting in the acquisition of five polycyclic cytochalasins featuring 5/6/5/8-fused tetracyclic and 5/6/6/7/5-fused pentacyclic skeletons. Two of the obtained polycyclic cytochalasins constituted unprecedented analogues, for which the trivial names cytochalasins J4 and J5 were proposed, whereas the others were identified as the known phomopchalasin A, phomopchalasin D and 21-acetoxycytochalasin J3. The structures of the compounds were determined by extensive spectral analysis, namely HR-ESIMS, ESIMS and 1D/2D NMR. The stereochemistry of cytochalasins J4 and J5 was proposed using their ROESY data, biosynthetic and mechanistic considerations and by comparison of their ECD spectra with those of related congeners. All compounds except for cytochalasins H and J were tested for antimicrobial and cytotoxic activity. Cytochalasins J4 and J5 showed neither antimicrobial nor cytotoxic activity in the tested concentrations, with only weak antiproliferative activity observable against KB3.1 cells. The actin disruptive properties of all cytochalasins obtained in this study and of the previously reported cytochalasins RKS-1778 and phomopchalasin N were examined, and monitored by fluorescence microscopy using human osteo-sarcoma (U2-OS) cells. Compared to their precursor molecules (cytochalasins H and J), phomopchalasins A and D, 21-acetoxycytochalasin J3, cytochalasins J4 and J5 revealed a strongly reduced activity on the F-actin network, highlighting that the macrocyclic ring is crucial for bioactivity.
Asunto(s)
Antineoplásicos , Citocalasinas , Humanos , Estructura Molecular , HongosRESUMEN
The genus Diaporthe (Diaporthaceae, Diaporthales) is a large group of fungi frequently reported as phytopathogens, with ubiquitous distribution across the globe. Diaporthe have traditionally been characterized by the morphology of their ana- and teleomorphic state, revealing a high degree of heterogeneity as soon as DNA sequencing was utilized across the different members of the group. Their relevance for biotechnology and agriculture attracts the attention of taxonomists and natural product chemists alike in context of plant protection and exploitation for their potential to produce bioactive secondary metabolites. While more than 1000 species are described to date, Africa, as a natural habitat, has so far been under-sampled. Several endophytic fungi belonging to Diaporthe were isolated from different plant hosts in Cameroon over the course of this study. Phylogenetic analyses based on DNA sequence data of the internal transcribed spacer region and intervening 5.8S nrRNA gene, and partial fragments of the calmodulin, beta-tubulin, histone and the translation elongation factor 1-α genes, demonstrated that these isolates represent four new species, i.e. D.brideliae, D.cameroonensis, D.pseudoanacardii and D.rauvolfiae. Moreover, the description of D.isoberliniae is here emended, now incorporating the morphology of beta and gamma conidia produced by two of our endophytic isolates, which had never been documented in previous records. Moreover, the paraphyletic nature of the genus is discussed and suggestions are made for future revision of the genus.
RESUMEN
During the course of a study on the biodiversity of endophytes from Cameroon, a fungal strain was isolated. A multigene phylogenetic inference using five DNA loci revealed that this strain represents an undescribed species of Diaporthe, which is introduced here as D.breyniae. Investigation into the chemistry of this fungus led to the isolation of two previously undescribed secondary metabolites for which the trivial names fusaristatins G (7) and H (8) are proposed, together with eleven known compounds. The structures of all of the metabolites were established by using one-dimensional (1D) and two-dimensional (2D) Nuclear Magnetic Resonance (NMR) spectroscopic data in combination with High-Resolution ElectroSpray Ionization Mass Spectrometry (HR-ESIMS) data. The absolute configuration of phomopchalasin N (4), which was reported for the first time concurrently to the present publication, was determined by analysis of its Rotating frame Overhauser Effect SpectroscopY (ROESY) spectrum and by comparison of its Electronic Circular Dichroism (ECD) spectrum with that of related compounds. A selection of the isolated secondary metabolites were tested for antimicrobial and cytotoxic activities, and compounds 4 and 7 showed weak antifungal and antibacterial activity. On the other hand, compound 4 showed moderate cytotoxic activity against all tested cancer cell lines with IC50 values in the range of 5.8-45.9 µM. The latter was found to be less toxic than the other isolated cytochalasins (1-3) and gave hints in regards to the structure-activity relationship (SAR) of the studied cytochalasins. Fusaristatin H (8) also exhibited weak cytotoxicity against KB3.1 cell lines with an IC50 value of 30.3 µM. Graphical abstract.
RESUMEN
A chemical study of the hydro-ethanol extract of the leaves of Combretum glutinosum resulted in the isolation of nine compounds, including 5-demethylsinensetin (1), umuhengerin (2), (20S,24R)-ocotillone (3), lupeol (4), ß-sitosterol (5), oleanolic acid (6), betulinic acid (7), corymbosin (8) and ß-sitosterol glucoside (9). Four compounds have been isolated for the first time from the genus Combretum [viz. (1), (2), (3) and (8)]. The crystal structures of flavonoid (2), C20H20O8, Z' = 2, and triterpene (3), C30H50O3, Z' = 1, have been determined for the first time; the latter confirmed the absolute configuration of native (20S,24R)-ocotillone previously derived from the crystal structures of related derivatives. The molecules of (3) are linked into supramolecular chains by intermolecular O-H...O hydrogen bonds. The crude extracts obtained by aqueous decoction and hydro-ethanolic maceration, as well as the nine isolated compounds, were tested for their anthelmintic activity on the larvae and adult worms of Haemonchus contortus, a hematophage that causes parasitic disorders in small ruminants. The evaluated anthelmintic activity showed that the extracts at different doses, as well as all the compounds tested at 150â µgâ ml-1, inhibited the migration of the larvae and the motility of the adult worms of the parasite compared with the phosphate buffer solution negative reference control. The best activity was obtained with flavonoids (1), (2) and (8) on both stages of the parasite. The flavones that showed good activity can be used for the further development of other derivatives, which could increase the anthelmintic efficacy.
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Antihelmínticos/farmacología , Antiinfecciosos/farmacología , Combretaceae/efectos de los fármacos , Combretum/química , Flavonas/farmacología , Flavonoides/química , Haemonchus/efectos de los fármacos , Larva/efectos de los fármacos , Hojas de la Planta/efectos de los fármacos , Animales , Antihelmínticos/química , Antihelmínticos/uso terapéutico , Antiinfecciosos/química , Cristalografía por Rayos X , Flavonas/química , Flavonoides/farmacología , Haemonchus/crecimiento & desarrollo , Enlace de Hidrógeno , Hojas de la Planta/químicaRESUMEN
Senegalin (1), a new phenylpropanoid has been isolated from the stem bark of Ekebergia senegalensis A. Juss. along with twelve known secondary metabolites including coumarins 2-5, 4-hydroxy-3,5-methylbenzoic acid (6), pentacyclic triterpenoids 7-9, acyclic triterpenoids 10 and 11 and steroids 12 and 13, respectively. Their structures were elucidated with the help of spectroscopic techniques including 1 D- and 2 D-NMR. The antibacterial activity of the major compounds (2, 9-11) was evaluated on five bacterial strains. However, only compounds 2 and 11 showed a weak inhibition against Bacillus subtilis and Pseudomonas agarici. Furthermore, the chemotaxonomic significance of these compounds has also been elaborated.
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Meliaceae , Triterpenos , Corteza de la Planta , PseudomonasRESUMEN
Four new iridoids viz., plumeridoids A, B, and C and epiplumeridoid C were isolated from the stem bark of Plumeria rubra Linn. together with twenty-four known compounds viz., 1-( P-hydroxyphenyl)propan-1-one, isoplumericin, plumericin, dihydroplumericin, allamcin, fulvoplumerin, allamandin, plumieride, P- E-coumaric acid, 2,6-dimethoxy- P-benzoquinone, scopoletin, cycloart-25-en-3 beta,24-diol, 2,4,6-trimethoxyaniline, ajunolic acid, ursolic acid, oleanolic acid, beta-amyrin acetate, betulinic acid, lupeol and its acetate, 2,3-dihydroxypropyl octacosanoate, glucoside of beta-sitosterol, and a mixture of common sterols (stigmasterol and beta-sitosterol). Their structures were determined by means of spectroscopic data including HREIMS, 1H NMR, 13C NMR, 2D NMR (HMQC, HMBC, NOESY) and by comparison with published data. All but one of thirteen tested compounds exhibited antifungal, antialgal, and/or antibacterial activities.
Asunto(s)
Antibacterianos/farmacología , Apocynaceae/química , Iridoides/farmacología , Corteza de la Planta/química , Tallos de la Planta/química , Antibacterianos/química , Bacterias/efectos de los fármacos , Iridoides/química , Estructura Molecular , Corteza de la Planta/metabolismo , Tallos de la Planta/metabolismoRESUMEN
The study of the chemical constituents of the stem bark of Teclea afzelii (Rutaceae) has resulted in the isolation and characterization of four furoquinoline alkaloids, namely kokusaginine (1), tecleaverdoornine (2), maculine (3) and montrifoline (4) together with lupeol (5) and beta-sitosterol glucopyranoside (6). The structures of the isolated compounds were elucidated based on spectroscopic studies. The antimalarial activity of compounds 1-4 against Plasmodium falciparum in vitro shows partial suppression of parasitic growth.
Asunto(s)
Alcaloides/farmacología , Antimaláricos/farmacología , Plasmodium falciparum/efectos de los fármacos , Quinolinas/farmacología , Rutaceae/química , Alcaloides/aislamiento & purificación , Antimaláricos/aislamiento & purificación , Dioxoles , Furanos/aislamiento & purificación , Furanos/farmacología , Estructura Molecular , Corteza de la Planta/química , Extractos Vegetales/farmacología , Plasmodium falciparum/crecimiento & desarrollo , Quinolinas/aislamiento & purificaciónRESUMEN
From the extracts of all parts of the plant Helichrysum cameroonense, five compounds were isolated and identified. One of them, a ceramide, named cameroonemide A (1), is reported for the first time as a new natural product. Its structure was determined by comprehensive analyses of their 1D and 2D NMR and HR-EI-MS spectral data. The remaining four known compounds were identified by comparing their spectroscopic data with those reported in the literature as kaurenoic acid (2), 3-acetyloxykaurenoic acid (3), beta-sitosterol (4), and beta-sitosterol glucopyranoside (5). Preliminary studies showed that 3-acetyloxykaurenoic acid (3) inhibited the alga Chlorella fusca, while kaurenoic acid (2) showed strong antibacterial activity against Bacillus megaterium.
Asunto(s)
Antibacterianos/aislamiento & purificación , Bacillus megaterium/efectos de los fármacos , Ceramidas/aislamiento & purificación , Helichrysum/química , Antibacterianos/química , Antibacterianos/farmacología , Camerún , Ceramidas/química , Ceramidas/farmacología , Pruebas de Sensibilidad Microbiana , Estructura Molecular , Resonancia Magnética Nuclear BiomolecularRESUMEN
Two new tetracyclic polyketides with a spirocenter, simplicilones A (1) and B (2) were isolated from the broth-culture of the endophytic fungus Simplicilliumsubtropicum (SPC3) in the course of our screening for new bioactive secondary metabolites. This endophytoic fungus is naturally harboured in the fresh bark of the Cameroonian medicinal plant Duguetia staudtii (Engl. and Diels) Chatrou. The planar structures of the simplicilones were elucidated by MS and 1D as well as 2D NMR spectroscopic techniques. The relative configuration was assigned by NOESY experiments in conjunction with coupling constants; subsequently, the absolute configurations were assigned by the modified Mosher's method. The compounds showed weak cytotoxic effects against the cell line KB3.1 (in vitro cytotoxicity (IC50) = 25 µg/mL for 1, 29 µg/mL for 2), but were inactive against the tested Gram-positive and Gram-negative bacteria as well as fungi.
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One of the major problems with the formulation of herbal medicines is the quality control of plant material to ensure its efficacy and safety. Quality control of medicinal plants requires analysis of many bioactive compounds present in the plant. C-alkylated flavonoids are an important bioactive subclass of flavonoids. A simple, rapid, sensitive and selective method is presented here for the quantification of bioactive C-alkylated flavonoids. This is the first quantitative method for analysis of C-alkylated flavonoids based on the multiple reaction monitoring (MRM) approach so far. This study focuses on method development for quantification of bioactive C-alkylated flavonoids. Quantification of a total of five C-alkylated flavonoids was done employing the MRM approach on an HPLC-QqQ-MS instrument. LODs and LOQs for quantified flavonoids were in the range of 0.41-1.32 and 1.23-3.96 ng/mL, respectively. Linear calibration curves between 25 and 1500 ng/mL were obtained with the regression coefficients of ≥0.996. Accuracy (% bias) and precision (% RSD) of the analyses were found to be less than 5%. Developed HPLC-ESI-MS/MS can be employed as a quality control method of plant raw materials.
Asunto(s)
Cromatografía Líquida de Alta Presión/métodos , Fabaceae/química , Flavonoides/análisis , Extractos Vegetales/química , Espectrometría de Masas en Tándem/métodos , Límite de Detección , Modelos Lineales , Modelos Químicos , Reproducibilidad de los ResultadosRESUMEN
Three new metabolites, microsphaeropsones A-C (1-3) with a unique oxepino[2,3-b]chromen-6-one (ring-enlarged xanthone) skeleton, were isolated from the endophytic fungus Microsphaeropsis species, co-occurring with their putative biogenetic anthraquinoide precursors citreorosein (4) and emodin (5). From another Microsphaeropsis species, large amounts of fusidienol A (8 a), smaller amounts of emodin (5), the known aromatic xanthones 9 a and 9 b, the new 3,4-dihydrofusidienol A (8 b), and the new aromatic xanthone 9 c were isolated. The endophyte Seimatosporium species produced a new aromatic xanthone, seimatoxanthone A (10), and 3,4-dihydroglobosuxanthone A (12), closely related to alpha-diversolonic ester (13) from Microdiplodia sp.. The structures were determined mainly by extensive 1D and 2D NMR experiments and supported by X-ray single-crystal analysis of 1 and the oxidation product 7. The absolute configurations of the microsphaeropsones A-C (1-3) were established by comparison of the electronic and vibrational circular dichroism (ECD and VCD) spectra of 1 with time-dependent DFT (TDDFT) and DFT calculations by using either the solid-state structures or DFT-optimized geometries as inputs. Preliminary studies indicated that 1, 2, and enone 7 showed antibacterial, fungicidal, and algicidal properties.
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Cromonas/química , Cromonas/aislamiento & purificación , Hongos/química , Oxepinas/química , Xantonas/química , Xantonas/aislamiento & purificación , Bacterias/efectos de los fármacos , Productos Biológicos/química , Productos Biológicos/aislamiento & purificación , Productos Biológicos/farmacología , Chlorella/efectos de los fármacos , Cromonas/farmacología , Dicroismo Circular , Hidrogenación , Espectroscopía de Resonancia Magnética , Xantonas/farmacologíaRESUMEN
Two new prenylated anthronoids, harunmadagascarins A and B, were isolated from the stem bark of Harungana madagascariensis along with six known compounds including two anthronoids: harunganol B and harungin anthrone, one benzophenone: methyl 3-formyl-2,4-dihydroxy-6-methyl benzoate and three pentacyclic triterpenes: friedelin, lupeol and betulinic acid. Harunmadagascarins A and B were characterized as 8,9-dihydroxy-4,4-bis-(3,3-dimethylallyl)-6-methyl-2,3-(2,2-dimethylpyrano)anthrone and 8,9-dihydroxy-4,4,5-tris-(3,3-dimethylallyl)-6-methyl-2,3-(2,2-dimethylpyrano)anthrone, respectively. The structures of these secondary metabolites were determined by spectroscopic means and comparison with the published data. Methyl 3-formyl-2,4-dihydroxy-6-methyl benzoate was isolated for the first time from a plant. Harunmadagascarins A and B, harunganol B and harungin anthrone exhibited significant antioxidant activity.
Asunto(s)
Antracenos/química , Antioxidantes/química , Clusiaceae/química , Corteza de la Planta/química , Depuradores de Radicales Libres/química , Estructura Molecular , Tallos de la Planta/químicaRESUMEN
The absolute configurations of plumericin (1) and isoplumericin (2), isolated from Plumeria rubra, were re-assigned based on a combination of X-ray crystal-structure determination and quantum-mechanical calculations of their circular dichroism (CD) spectra. The experimental CD spectra showed an excellent match with those calculated for the (1S,5R,8R,9R,10R) absolute configuration (corresponding to ent-1 and ent-2, resp.), opposite to that generally accepted and published in the literature. Since the (false) plumericin configuration has been often used to derive the absolute configuration of related iridoids by chemical correlation, their absolute configurations also have to be reconsidered.
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Apocynaceae/química , Indenos/química , Iridoides , Modelos Moleculares , Estructura MolecularRESUMEN
INTRODUCTION: The expression of diverse resistance mechanisms in cancer cells is one of the major barriers to successful cancer chemotherapy. METHODS: In the present study, we assessed the cytotoxicity of two naturally occurring flavonoids dorsmanin F (1, a flavanone) and poinsettifolin B (2, a chalcone) against 9 drug-sensitive and multidrug-resistant (MDR) cancer cell lines. The resazurin reduction assay was used to evaluate the cytotoxicity of these compounds, whilst caspase-Glo assay was used to detect caspase activation. Cell cycle, mitochondrial membrane potential (MMP) and levels of reactive oxygen species (ROS) were all analysed via flow cytometry. RESULTS: Compounds 1 and 2 displayed cytotoxic effects with IC50 values below 34 µM in all the 9 tested cancer cell lines. The IC50 values for flavanone 1 and chalcone 2 ranged from 5.34 µM and 1.94 µM (towards leukaemia CCRF-CEM cells) to 33.30 µM and 28.92 µM (towards MDA-MB-231-BCRP cells), respectively, and from 0.20 µM (against CCRF-CEM cells) to 195.12 µM (against CEM/ADR5000 cells) for doxorubicin. The compounds induced apoptosis in CCRF-CEM leukaemia cells, mediated by MMP disruption and increased ROS production. CONCLUSIONS: Dorsmain F and poinsettifolin B are potential cytotoxic natural products that deserve more investigations to develop novel antineoplastic drugs against multifactorial drug-resistant cancers.
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Antineoplásicos Fitogénicos/farmacología , Chalconas/farmacología , Resistencia a Múltiples Medicamentos , Resistencia a Antineoplásicos , Flavonoides/farmacología , Apoptosis/efectos de los fármacos , Caspasas/metabolismo , Ciclo Celular/efectos de los fármacos , Línea Celular Tumoral/efectos de los fármacos , Humanos , Concentración 50 Inhibidora , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Estructura Molecular , Especies Reactivas de Oxígeno/metabolismoRESUMEN
Villarinol (1), a new alkenoyloxy alkenol metabolite, has been isolated from the dichloromethane extract of Villaria odorata, an endemic Rubiaceae Philippine plant, along with the known compounds stigmasterol and 4-hydroxybenzaldehyde. The structure of 1 was elucidated on the basis of spectroscopic and spectrometric studies. The extracts of V. odorata exhibited moderate inhibition against Mycobacterium tuberculosis H37Rv, based on the colorimetric microplate alamar blue assay.
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Rubiaceae/química , Antituberculosos/química , Antituberculosos/farmacología , Benzaldehídos/química , Benzaldehídos/farmacología , Pruebas de Sensibilidad Microbiana , Mycobacterium tuberculosis/efectos de los fármacos , Extractos Vegetales/química , Extractos Vegetales/farmacología , Estigmasterol/química , Estigmasterol/farmacologíaRESUMEN
Eight compounds were isolated from the stem bark of the plant Afraegle paniculata. One of them, a dimethyl ether of S-trans-marmin (1), is reported as a new natural product. The structures were determined by comprehensive analyses of their 1D and 2D NMR spectroscopic and HREIMS data. The remaining seven known compounds, identified by comparing their spectroscopic data with those reported in the literature, were S-trans-marmin (2), psoralene (3), bergaptene (4), imperatorin (5), 2-(4-hydroxy-3,5-dimethoxyphenyl)-3-hydroxymethyl-2,3-dihydro- 1,4,5-trioxaphenanthren-6-one (6), xanthoxyletin (7), and beta-sitosterol glucopyranoside. Preliminary studies indicated that compounds 2, 3, 5, and 7 showed potent antibacterial, fungicidal, and algicidal properties, while 6 showed only moderate algicidal property.
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Antibacterianos/aislamiento & purificación , Antifúngicos/aislamiento & purificación , Cumarinas/aislamiento & purificación , Rutaceae/química , Antibacterianos/química , Antibacterianos/farmacología , Antifúngicos/química , Antifúngicos/farmacología , Cumarinas/química , Cumarinas/farmacología , Espectrometría de Masas , Pruebas de Sensibilidad Microbiana , Resonancia Magnética Nuclear Biomolecular , Corteza de la Planta/químicaRESUMEN
Pycnanthus anglonensis is known for its medicinal value. This paper deals with a phytochemical investigation of this species, from which pycnangloside (1), a new cerebroside has been isolated. Its structure was determined by comprehensive analyses of its 1D and 2D NMR spectroscopic, and ESI mass spectrometric data. Four known compounds were also isolated and identified as biochanin A, formonentin, beta-sitosterol, and beta-sitosterol glucopyranoside.