RESUMEN
From the leaves of Tithonia diversifolia, nine sesquiterpenoids (1-9), including two new ones (1, 2) were isolated and structurally determined. Their chemical structures were elucidated by extensive analyses of HRESIMS and NMR spectral data, as well as comparison with the literature. All of the isolated compounds (except compounds 7, 8, 9) significantly exhibited cytotoxic activity against four human cancer cell lines (KB, HepG2, A549 and MCF7), with IC50 values ranging from 0.29-17.0 µM, which was in the same range as the positive control ellipticine or even lower. Further, the apoptosis induction of two new compounds 1 and 2 were also investigated and reported. While compound 2 did not induce cell apoptosis in KB cells at test concentrations, compound 1 was found to possess anti-proliferative activity through concentration-dependently inducing cell cycle arrest at S phase, morphological changes, activation of caspase 3, and an increase in the early-stage apoptosis of KB cells at a concentration of 7.26 µM.
RESUMEN
The Streptomyces strain G222, isolated from a Vietnamese marine sediment, was confidently identified by 16S rRNA gene sequencing. Its AcOEt crude extract was successfully analyzed using non-targeted LC-MS/MS analysis, and molecular networking, leading to a putative annotation of its chemical diversity thanks to spectral libraries from GNPS and in silico metabolite structure prediction obtained from SIRIUS combined with the bioinformatics tool conCISE (Consensus Annotation Propagation of in silico Elucidations). This dereplication strategy allowed the identification of an interesting cluster of a series of putative cyclic and linear lipopeptides of the lichenysin and surfactin families. Lichenysins (3-7) were isolated from the sub-fraction, which showed significant anti-biofilm activity against Pseudomonas aeruginosa MUC-N1. Their structures were confirmed by detailed 1D and 2D NMR spectroscopy (COSY, HSQC, HMBC, TOCSY, ROESY) recorded in CD3OH, and their absolute configurations were determined using the modified Marfey's method. The isolated lichenysins showed anti-biofilm activity at a minimum concentration of 100 µM. When evaluated for antibacterial activity against a panel of Gram-positive and Gram-negative strains, two isolated lichenysins exhibited selective activity against the MRSA strain without affecting its growth curve and without membranotropic activity. This study highlights the power of the MS/MS spectral similarity strategy using computational methods to obtain a cross-validation of the annotated molecules from the complex metabolic profile of a marine sediment-derived Streptomyces extract. This work provides the first report from a Streptomyces strain of combined cyclic and linear lichenysins and surfactins, known to be characteristic compounds of the genus Bacillus.
Asunto(s)
Sedimentos Geológicos , Espectrometría de Masas en Tándem , Humanos , Cromatografía Liquida , ARN Ribosómico 16S , VietnamRESUMEN
Induced by the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the COVID-19 pandemic underlined the clear need for antivirals against coronaviruses. In an effort to identify new inhibitors of SARS-CoV-2, a screening of 824 extracts prepared from various parts of 400 plant species belonging to the Rutaceae and Annonaceae families was conducted using a cell-based HCoV-229E inhibition assay. Due to its significant activity, the ethyl acetate extract of the leaves of Clausena harmandiana was selected for further chemical and biological investigations. Mass spectrometry-guided fractionation afforded three undescribed phenolic lipids (1-3), whose structures were determined via spectroscopic analysis. The absolute configurations of 1 and 2 were determined by analyzing Mosher ester derivatives. The antiviral activity against SARS-CoV-2 was subsequently shown, with IC50 values of 0.20 and 0.05 µM for 2 and 3, respectively. The mechanism of action was further assessed, showing that both 2 and 3 are inhibitors of coronavirus entry by acting directly on the viral particle. Phenolic lipids from Clausena harmandiana might be a source of new antiviral agents against human coronaviruses.
Asunto(s)
COVID-19 , Clausena , Humanos , SARS-CoV-2 , Clausena/química , Pandemias , Antivirales/farmacología , Hojas de la Planta , LípidosRESUMEN
A comprehensive metabolomic strategy, integrating 1H NMR and MS-based multi-block modelling in conjunction with multi-informational molecular networking, has been developed to discriminate sponges of the order Haplosclerida, well known for being taxonomically contentious. An in-house collection of 33 marine sponge samples belonging to three families (Callyspongiidae, Chalinidae, Petrosiidae) and four different genera (Callyspongia, Haliclona, Petrosia, Xestospongia) was investigated using LC-MS/MS, molecular networking, and the annotations processes combined with NMR data and multivariate statistical modelling. The combination of MS and NMR data into supervised multivariate models led to the discrimination of, out of the four genera, three groups based on the presence of metabolites, not necessarily previously described in the Haplosclerida order. Although these metabolomic methods have already been applied separately, it is the first time that a multi-block untargeted approach using MS and NMR has been combined with molecular networking and statistically analyzed, pointing out the pros and cons of this strategy.
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Poríferos , Espectrometría de Masas en Tándem , Animales , Cromatografía Liquida , Espectroscopía de Resonancia Magnética , Metabolómica/métodos , Poríferos/químicaRESUMEN
Libraries of microorganisms have served as a cornerstone of therapeutic drug discovery, though the continued re-isolation of known natural product chemical entities has remained a significant obstacle to discovery efforts. A major contributing factor to this redundancy is the duplication of bacterial taxa in a library, which can be mitigated through the use of a variety of DNA sequencing strategies and/or mass spectrometry-informed bioinformatics platforms so that the library is created with minimal phylogenetic, and thus minimal natural product overlap. IDBac is a MALDI-TOF mass spectrometry-based bioinformatics platform used to assess overlap within collections of environmental bacterial isolates. It allows environmental isolate redundancy to be reduced while considering both phylogeny and natural product production. However, manually selecting isolates for addition to a library during this process was time intensive and left to the researcher's discretion. Here, we developed an algorithm that automates the prioritization of hundreds to thousands of environmental microorganisms in IDBac. The algorithm performs iterative reduction of natural product mass feature overlap within groups of isolates that share high homology of protein mass features. Employing this automation serves to minimize human bias and greatly increase efficiency in the microbial strain prioritization process.
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Productos Biológicos , Biología Computacional , Bacterias/genética , Productos Biológicos/química , Biblioteca de Genes , Humanos , Filogenia , Espectrometría de Masa por Láser de Matriz Asistida de Ionización DesorciónRESUMEN
ORPphilins are bioactive natural products that strongly and selectively inhibit the growth of some cancer cell lines and are proposed to target intracellular lipid-transfer proteins of the oxysterol-binding protein (OSBP) family. These conserved proteins exchange key lipids, such as cholesterol and phosphatidylinositol 4-phosphate (PI(4)P), between organelle membranes. Among ORPphilins, molecules of the schweinfurthin family interfere with intracellular lipid distribution and metabolism, but their functioning at the molecular level is poorly understood. We report here that cell line sensitivity to schweinfurthin G (SWG) is inversely proportional to cellular OSBP levels. By taking advantage of the intrinsic fluorescence of SWG, we followed its fate in cell cultures and show that its incorporation at the trans-Golgi network depends on cellular abundance of OSBP. Using in vitro membrane reconstitution systems and cellular imaging approaches, we also report that SWG inhibits specifically the lipid transfer activity of OSBP. As a consequence, post-Golgi trafficking, membrane cholesterol levels, and PI(4)P turnover were affected. Finally, using intermolecular FRET analysis, we demonstrate that SWG directly binds to the lipid-binding cavity of OSBP. Collectively these results describe SWG as a specific and intrinsically fluorescent pharmacological tool for dissecting OSBP properties at the cellular and molecular levels. Our findings indicate that SWG binds OSBP with nanomolar affinity, that this binding is sensitive to the membrane environment, and that SWG inhibits the OSBP-catalyzed lipid exchange cycle.
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Transporte Biológico/efectos de los fármacos , Lípidos/genética , Receptores de Esteroides/metabolismo , Estilbenos/metabolismo , Proteínas Portadoras/química , Proteínas Portadoras/genética , Retículo Endoplásmico/química , Retículo Endoplásmico/genética , Fluorescencia , Humanos , Lípidos/química , Unión Proteica/genética , Transporte de Proteínas/genética , Receptores de Esteroides/química , Estilbenos/química , Red trans-Golgi/química , Red trans-Golgi/genéticaRESUMEN
Maesa membranacea A. DC. (Primulaceae) is a plant species that has been frequently used by practitioners of the traditional ethnobotany knowledge from northern and central Vietnam. However, the chemical constituents of the plant remained unknown until recently. Chromatographic separation of a chloroform-soluble fraction of extract from leaves of M. membranacea led to the isolation of two new polyesterified ursane triterpenes (1-2) and two known apocarotenoids: (+)-dehydrovomifoliol (3) and (+)-vomifoliol (4). The chemical structures of the undescribed triterpenoids were elucidated using 1D and 2D MNR and HRESIMS spectral data as 2α,6ß,22α-triacetoxy-11α-(2-methylbutyryloxy)-urs-12-ene-3α,20ß-diol (1) and 2α,6ß,22α-triacetoxy-urs-12-ene-3α,11α,20ß-triol (2). The newly isolated triterpenoids were tested for their cytotoxic activity in vitro against two melanoma cell lines (HTB140 and A375), normal skin keratinocytes (HaCaT), two colon cancer cell lines (HT29 and Caco-2), two prostate cancer cell lines (DU145 and PC3) and normal prostate epithelial cells (PNT-2). Doxorubicin was used as a reference cytostatic drug. The 2α,6ß,22α-triacetoxy-11α-(2-methylbutyryloxy)-urs-12-ene-3α,20ß-diol demonstrated cytotoxic activity against prostate cancer cell lines (Du145-IC50 = 35.8 µg/mL, PC3-IC50 = 41.6 µg/mL), and at a concentration of 100 µg/mL reduced viability of normal prostate epithelium (PNT-2) cells by 41%.
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Antineoplásicos Fitogénicos , Citotoxinas , Maesa/química , Neoplasias/tratamiento farmacológico , Hojas de la Planta/química , Triterpenos , Antineoplásicos Fitogénicos/química , Antineoplásicos Fitogénicos/aislamiento & purificación , Antineoplásicos Fitogénicos/farmacología , Células CACO-2 , Citotoxinas/química , Citotoxinas/aislamiento & purificación , Citotoxinas/farmacología , Células HT29 , Humanos , Neoplasias/metabolismo , Neoplasias/patología , Células PC-3 , Triterpenos/química , Triterpenos/aislamiento & purificación , Triterpenos/farmacologíaAsunto(s)
Hemangioma Cavernoso del Sistema Nervioso Central , Hemangioma Cavernoso del Sistema Nervioso Central/patología , Humanos , Animales , Complejo Represivo Polycomb 1/genética , Complejo Represivo Polycomb 1/metabolismo , Complejo Represivo Polycomb 1/antagonistas & inhibidores , Ratones , MasculinoRESUMEN
Two new phenanthroquinolizidine alkaloids (1: and 2: ) and a new piperidine derivative (3: ) were isolated from the leaves of Pilea aff. martinii together with 3 known alkaloids: julandine (4: ), cryptopleurine (5: ), and 1,3,6,6-tetramethyl-5,6,7,8-tetrahydro-isoquinolin-8-one (6: ). Their structures were determined by spectral data analyses including mass spectrometry and 2-dimensional nuclear magnetic resonance data. The absolute configurations of 1: -3: were established by comparison of their experimental circular dichroism data with the calculated electronic circular dichroism spectra. The isolated compounds were evaluated for their cytotoxicity against 4 cancer cell lines: KB (mouth epidermal carcinoma cells), HepG-2 (human liver hepatocellular carcinoma cells), LU-1 (human lung adenocarcinoma cells), and MCF-7 (human breast cancer cells). The new phenanthroquinolizidine pileamartine D (2: ) showed strong and selective proliferation inhibition toward KB and HepG-2 cells with IC50 values of 25 and 27 nM, respectively. Pileamartine C (1: ), julandine (4: ), and cryptopleurine (5: ) exhibited cytotoxicity against 4 tested cancer cell lines with IC50 values less than 1 µM.
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Alcaloides/aislamiento & purificación , Citotoxinas/aislamiento & purificación , Hojas de la Planta/química , Urticaceae , Línea Celular Tumoral/efectos de los fármacos , Dicroismo Circular , Células Hep G2/efectos de los fármacos , Humanos , Células MCF-7/efectos de los fármacos , Espectroscopía de Resonancia Magnética , Espectrometría de Masas , Urticaceae/químicaRESUMEN
Three new lavandulylated flavonoids, (2S,2''S)-6-lavandulyl-7,4'-dimethoxy-5,2'-dihydroxylflavanone (1), (2S,2''S)-6-lavandulyl-5,7,2',4'-tetrahydroxylflavanone (2), and (2''S)-5'-lavandulyl-2'-methoxy-2,4,4',6'-tetrahydroxylchalcone (3), along with seven known compounds 4-10 were isolated from culture broth of Streptomyces sp. G248. Their structures were established by spectroscopic data analysis, including 1D and 2D nuclear magnetic resonance (NMR), and high-resolution electrospray ionization mass spectrometry (HR-ESI-MS). The absolute configurations of 1-3 were resolved by comparison of their experimental and calculated electronic circular dichroism spectra. Compounds 1-3 exhibited remarkable antimicrobial activity. Whereas, two known compounds 4 and 5 exhibited inhibitory activity against Mycobacterium tuberculosis H37Rv with minimum inhibitory concentration (MIC) values of 6.0 µg/mL and 11.1 µg/mL, respectively.
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Antibióticos Antituberculosos/farmacología , Flavonoides/farmacología , Poríferos/microbiología , Streptomyces/química , Animales , Antibióticos Antituberculosos/química , Antibióticos Antituberculosos/aislamiento & purificación , Línea Celular Tumoral , Dicroismo Circular , Flavonoides/química , Flavonoides/aislamiento & purificación , Espectroscopía de Resonancia Magnética , Pruebas de Sensibilidad Microbiana , Estructura Molecular , Mycobacterium tuberculosis/efectos de los fármacos , Espectrometría de Masa por Ionización de Electrospray , VietnamRESUMEN
Four new compounds N-salicyl-3-hydroxyanthranilic acid methyl ester (1), N-(2'-dehydroxysalicyl)-3-hydroxyanthranilic acid methyl ester (2), methyl-4-ß-D-allopyranosyl-ferulate (3), and methyl-4-ß-D-gulopyranosyl-cinnamate (4), along with six known compounds (5-10), were isolated from the roots of Aconitum carmichelii Debx. Their structures were elucidated on the basis of spectral data analysis, including 1D, 2D-NMR, and HR-ESI-MS. Compounds 1 and 2 showed the inhibition of nitric oxide (NO) production with IC50 values of 9.13 and 19.94 µM, respectively.
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Aconitum/química , Cinamatos/química , Raíces de Plantas/química , ortoaminobenzoatos/química , Animales , Cinamatos/farmacología , Medicamentos Herbarios Chinos , Glucósidos/química , Glucósidos/farmacología , Espectroscopía de Resonancia Magnética , Ratones , Estructura Molecular , Óxido Nítrico/antagonistas & inhibidores , Óxido Nítrico/biosíntesis , Células RAW 264.7 , Espectrometría de Masa por Ionización de Electrospray , ortoaminobenzoatos/farmacologíaRESUMEN
Marine microorganisms are an invaluable source of novel active secondary metabolites possessing various biological activities. In this study, the extraction and isolation of the marine sediment Penicillium species collected in Vietnam yielded ten secondary metabolites, including sporogen AO-1 (1), 3-indolecarbaldehyde (2), 2-[(5-methyl-1,4-dioxan-2-yl)methoxy]ethanol (3), 2-[(2R-hydroxypropanoyl)amino]benzamide (4), 4-hydroxybenzandehyde (5), chrysogine (6), 3-acetyl-4-hydroxycinnoline (7), acid 1H-indole-3-acetic (8), cyclo (Tyr-Trp) (9), and 2',3'-dihydrosorbicillin (10). Their structures were identified by the analysis of 1D and 2D NMR data. Among the isolated compounds, 2-[(5-methyl-1,4-dioxan-2-yl)methoxy]ethanol (3) showed a strong inhibitory effect against Enterococcus faecalis with a minimum inhibitory concentration value of 32 µg/mL. Both 2-[(2R-hydroxypropanoyl)amino]benzamide (4) and 4-hydroxybenzandehyde (5) selectively inhibited E. coli with minimum inhibitory concentration values of 16 and 8 µg/mL, respectively. 2',3'-Dihydrosorbicillin (10) potentially inhibited α-glucosidase activity at a concentration of 2.0 mM (66.31%).
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Antibacterianos , Organismos Acuáticos , Enterococcus faecalis/crecimiento & desarrollo , Penicillium , Antibacterianos/química , Antibacterianos/metabolismo , Antibacterianos/farmacología , Organismos Acuáticos/química , Organismos Acuáticos/metabolismo , Estructura Molecular , Penicillium/química , Penicillium/metabolismo , VietnamRESUMEN
Chemical investigation of the methanol extract of the Vietnamese marine sponge Ircinia echinata led to the isolation of six new 9α-hydroxy-5α,6α-epoxysterols: 5α,6α-epoxycholesta-7,22(E)-dien-3ß,9α-diol (1), 5α,6α-epoxycholesta-7,24(28)-dien-3ß,9α-diol (2), (24R)-5α,6α-epoxy-24-ethyl-cholesta-7-en-3ß,9α-diol (3), 5α,6α-epoxycholesta-7-en-3ß,9α-diol (4), (24S)-5α,6α-epoxyergosta-7,22-dien-3ß,9α-diol (5), and (24R)-5α,6α-epoxy-24-methyl-cholesta-7-en-3ß,9α-diol (6) along with the known 5α-6α-epoxysterols: 5α,6α-epoxystigmasta-7-en-3ß-ol (7), 5α,6α-epoxystigmasta-7,22-dien-3ß-ol (8), and 5α,6α-epoxyergosta-7-en-3ß-ol (9). Their structures and their configurations were established on the basis of high resolution mass spectra and extensive 1D and 2D NMR spectroscopic data and by comparison with the literature. Their cytotoxic activity, evaluated against three human cancer cell lines, MCF-7, Hep-G2 and LU-1, revealed that only compounds 3 and 4 exhibited significant antiproliferative activity and compound 3 showed a selective inhibition towards the MCF-7 human breast cancer cells.
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Antineoplásicos/farmacología , Organismos Acuáticos/química , Compuestos Epoxi/farmacología , Poríferos/química , Esteroles/farmacología , Animales , Antineoplásicos/química , Antineoplásicos/aislamiento & purificación , Ensayos de Selección de Medicamentos Antitumorales , Compuestos Epoxi/química , Compuestos Epoxi/aislamiento & purificación , Células Hep G2 , Humanos , Células MCF-7 , Espectroscopía de Resonancia Magnética/métodos , Espectrometría de Masas/métodos , Estructura Molecular , Esteroles/química , Esteroles/aislamiento & purificación , VietnamRESUMEN
Using a time-of-flight secondary ion mass spectrometer equipped with an argon cluster ion for sputtering and a bismuth liquid metal ion source for analysis, both surfaces of leaves and fruits of Macaranga vedeliana, an endemic New Caledonian species, have been for the first time analyzed by a dual beam depth profiling. To prevent in-vacuum evaporation of the liquid content of the small glandular trichomes covering fruits and leaves surfaces and also to be able to analyze their liquid content while preventing any sublimation of the latter, the samples were kept frozen during the whole experiment using a nitrogen cooled sample holder. Thus, it was possible to demonstrate that vedelianin, an active metabolite of the family of prenylated stilbenes named schweinfurthins, is only located in these glandular trichomes.
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Argón/química , Bismuto/química , Euphorbiaceae/química , Espectrometría de Masas/métodos , Estilbenos/química , Frutas/química , Hojas de la Planta/química , PrenilaciónRESUMEN
Four new dammarane-type triterpenoids (1-4) and twelve known compounds (5-16) were isolated from the leaves of Viburnum sambucinum Reinw. ex Blume. Their structures were determined by spectral data analysis, including MS and 2D NMR. Cytotoxic activity evaluation in vitro against four cancer cell lines (KB, LU-1, HepG2 and MCF7) suggested that the octanor-dammarane derivatives were the main cytotoxic components of the leaves of V. sambucinum.
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Antineoplásicos Fitogénicos/química , Antineoplásicos Fitogénicos/farmacología , Triterpenos/química , Triterpenos/farmacología , Antineoplásicos Fitogénicos/aislamiento & purificación , Línea Celular Tumoral , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Neoplasias/tratamiento farmacológico , Hojas de la Planta/química , Triterpenos/aislamiento & purificación , Viburnum/química , DamaranosRESUMEN
With the aim of discovering new cytotoxic prenylated stilbenes of the schweinfurthin series, Macaranga tanarius was selected for detailed phytochemical investigation among 21 Macaranga species examined by using a molecular networking approach. From an ethanol extract of the fruits, seven new prenylated stilbenes, schweinfurthins K-Q (7-13), were isolated, along with vedelianin (1), schwenfurthins E-G (2-4), mappain (5), and methyl-mappain (6). The structures of the new compounds were established by spectroscopic data analysis. The relative configurations of compounds 8, 12, and 13 were determined based on ROESY NMR spectroscopic analysis. The cytotoxic activities of compounds 1-13 were evaluated against the human glioblastoma (U87) and lung (A549) cancer cell lines.
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Antineoplásicos Fitogénicos/aislamiento & purificación , Antineoplásicos Fitogénicos/farmacología , Euphorbiaceae/química , Estilbenos/aislamiento & purificación , Estilbenos/farmacología , Antineoplásicos Fitogénicos/química , Ensayos de Selección de Medicamentos Antitumorales , Flavonoides/química , Frutas/química , Humanos , Estructura Molecular , Resonancia Magnética Nuclear Biomolecular , Hojas de la Planta/química , Prenilación , Estilbenos/química , VietnamRESUMEN
Dereplication represents a key step for rapidly identifying known secondary metabolites in complex biological matrices. In this context, liquid-chromatography coupled to high resolution mass spectrometry (LC-HRMS) is increasingly used and, via untargeted data-dependent MS/MS experiments, massive amounts of detailed information on the chemical composition of crude extracts can be generated. An efficient exploitation of such data sets requires automated data treatment and access to dedicated fragmentation databases. Various novel bioinformatics approaches such as molecular networking (MN) and in-silico fragmentation tools have emerged recently and provide new perspective for early metabolite identification in natural products (NPs) research. Here we propose an innovative dereplication strategy based on the combination of MN with an extensive in-silico MS/MS fragmentation database of NPs. Using two case studies, we demonstrate that this combined approach offers a powerful tool to navigate through the chemistry of complex NPs extracts, dereplicate metabolites, and annotate analogues of database entries.
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Productos Biológicos/química , Espectrometría de Masas en Tándem/métodos , Cromatografía Liquida/métodos , Simulación por ComputadorRESUMEN
A screening of our actinomycete fraction library against the NCI-60 SKOV3 human tumor cell line led to the isolation of isopimara-2-one-3-ol-8,15-diene (1), lagumycin B (2), dehydrorabelomycin (3), phenanthroviridone (4), and WS-5995 A (5). These secondary metabolites were produced by a Micromonospora sp. isolated from sediment collected off the Cát Bà peninsula in the East Sea of Vietnam. Compound 1 is a novel Δ(8,9)-pimarane diterpene, representing one of approximately 20 actinomycete-produced diterpenes reported to date, while compound 2 is an angucycline antibiotic that has yet to receive formal characterization. The structures of 1 and 2 were elucidated by combined NMR and MS analysis and the absolute configuration of 1 was assigned by analysis of NOESY NMR and CD spectroscopic data. Compounds 2-5 exhibited varying degrees of cytotoxicity against a panel of cancerous and non-cancerous cell lines. Overall, this study highlights our collaborative efforts to discover novel biologically active molecules from the large, underexplored, and biodiversity-rich waters of Vietnam's East Sea.
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Abietanos/química , Antineoplásicos/química , Antineoplásicos/farmacología , Micromonospora/química , Micromonospora/metabolismo , Animales , Línea Celular Tumoral , Femenino , Humanos , Estructura Molecular , Océanos y Mares , Neoplasias Ováricas/tratamiento farmacológico , VietnamRESUMEN
A rapid screening by (1)H and (1)H-(13)C HSQC NMR spectroscopy of EtOAc extracts of Endiandra and Beilschmiedia species allowed the selection of Beilschmiedia ferruginea leaves and flowers extract for a chemical investigation, leading to the isolation of 11 new tetracyclic endiandric acid analogues, named ferrugineic acids A-K (1-11). Their structures were determined by 1D and 2D NMR spectroscopic analysis in combination with HRMS data. These compounds were assayed for Bcl-xL and Mcl-1 binding affinities. Ferrugineic acids B, C, and J (2, 3, and 10) exhibited significant binding affinity for both antiapoptotic proteins Bcl-xL (Ki = 19.2, 12.6, and 19.4 µM, respectively) and Mcl-1 (Ki = 14.0, 13.0, and 5.2 µM, respectively), and ferrugineic acid D (4) showed only significant inhibiting activity for Mcl-1 (Ki = 5.9 µM).
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Ácidos Carboxílicos/farmacología , Lauraceae/química , Proteínas Proto-Oncogénicas c-bcl-2/antagonistas & inhibidores , Proteína Destructora del Antagonista Homólogo bcl-2/antagonistas & inhibidores , Proteína bcl-X/antagonistas & inhibidores , Apoptosis/efectos de los fármacos , Ácidos Carboxílicos/química , Estructura Molecular , Resonancia Magnética Nuclear Biomolecular , VietnamRESUMEN
Eight new aryltetralin lignans, cleisindosides A-F (1-6), picroburseranin (7), and 7-hydroxypicropolygamain (8), were isolated from the fruits of Cleistanthus indochinensis (Euphorbiaceae). The structures of the isolates were established on the basis of their one- and two-dimensional NMR spectral data, as well as their mass spectrometric data. Compound 7 was found to have potent cytotoxicity against oral epidermoid carcinoma cells with an IC50 value of 0.062 µM, whereas glycosylation to 3 (IC50 7.5 µM) and stereochemical changes to 8 (IC50 10.8 µM) led to marked decreases in biological activity. Thus, it was determined that the C-7 and C-8' positions are critical for the biological activity of the lignans from this plant.