Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 194
Filtrar
1.
Toxins (Basel) ; 13(2)2021 Feb 12.
Artículo en Inglés | MEDLINE | ID: mdl-33673235

RESUMEN

We are investigating plant species from the Canadian prairie ecological zone by phenotypic cell assays to discover toxins of biological interest. We provide the first report of the effects of extracts prepared from the shrub Symphoricarpos occidentalis in several human cell lines. S. occidentalis (Caprifoliaceae) extracts are cytotoxic, and, strikingly, treated cells undergo light-dependent vacuolation near the nucleus. The range of irradiation is present in standard ambient light and lies in the visible range (400-700 nm). Vacuolization in treated cells can be induced with specific wavelengths of 408 or 660 nm at 1 J/cm2 energies. Vacuolated cells show a striking phenotype of a large perinuclear vacuole (nuclear associated vacuole, NAV) that is distinct from vesicles observed by treatment with an autophagy-inducing agent. Treatment with S. occidentalis extracts and light induces an intense lamin A/C signal at the junction of a nuclear vacuole and the nucleus. Further study of S. occidentalis extracts and vacuolation provide chemical tools that may contribute to the understanding of nuclear envelope organization and human cell biology.

2.
Future Med Chem ; 13(5): 487-504, 2021 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-33565317

RESUMEN

Oceans harbor a vast biodiversity that is not represented in terrestrial habitats. Marine sponges have been the richest source of marine natural products reported to date, and sponge-derived natural products have served as inspiration for the development of several drugs in clinical use. However, many promising sponge-derived drug candidates have been stalled in clinical trials due to lack of efficacy, off-target toxicity, metabolic instability or poor pharmacokinetics. One possible solution to this high clinical failure rate is to design drug delivery systems that deliver drugs in a controlled and specific manner. This review critically analyzes drugs/drug candidates inspired by sponge natural products and the potential use of drug delivery systems as a new strategy to enhance the success rate for translation into clinical use.

3.
ACS Omega ; 5(40): 25593-25604, 2020 Oct 13.
Artículo en Inglés | MEDLINE | ID: mdl-33073085

RESUMEN

The marine natural product latonduine A (1) shows F508del-cystic fibrosis transmembrane regulator (CFTR) corrector activity in cell-based assays. Pull-down experiments, enzyme inhibition assays, and siRNA knockdown experiments suggest that the F508del-CFTR corrector activities of latonduine A and a synthetic analogue MCG315 (4) result from simultaneous inhibition of PARP3 and PARP16. A library of synthetic latonduine A analogs has been prepared in an attempt to separate the PARP3 and PARP16 inhibitory properties of latonduine A with the goal of discovering selective small-molecule PARP3 and PARP16 inhibitory cell biology tools that could confirm the proposed dual-target F508del-CFTR corrector mechanism of action. The structure activity relationship (SAR) study reported herein has resulted in the discovery of the modestly potent (IC50 3.1 µM) PARP3 selective inhibitor (±)-5-hydroxy-4-phenyl-2,3,4,5-tetrahydro-1H-benzo[c]azepin-1-one (5) that shows 96-fold greater potency for inhibition of PARP3 compared with its inhibition of PARP16 in vitro and the potent (IC50 0.362 µM) PARP16 selective inhibitor (±)-7,8-dichloro-5-hydroxy-4-(pyridin-2-yl)-2,3,4,5-tetrahydro-1H-benzo[c]azepin-1-one (6) that shows 205-fold selectivity for PARP16 compared with PARP3 in vitro. At 1 or 10 µM, neither 5 or 6 alone showed F508del-CFTR corrector activity, but when added together at 1 or 10 µM each, the combination exhibited F508del-CFTR corrector activity identical to 1 or 10 µM latonduine A (1), respectively, supporting its novel dual PARP target mechanism of action. Latonduine A (1) showed additive in vitro corrector activity in combination with the clinically approved corrector VX809, making it a potential new partner for cystic fibrosis combination drug therapies.

4.
J Nat Prod ; 2020 Oct 30.
Artículo en Inglés | MEDLINE | ID: mdl-33124806

RESUMEN

Synthetic analogues of the marine natural product sintokamides have been prepared in order to investigate the structure-activity relationships for the androgen receptor N-terminal domain (AR NTD) antagonist activity of the sintokamide scaffold. An in vitro LNCaP cell-based transcriptional activity assay with an androgen-driven luciferase (Luc) reporter was used to monitor the potency of analogues. The data have shown that the chlorine atoms on the leucine side chains are essential for potent activity. Analogues missing the nonchlorinated methyl groups of the leucine side chains (C-1 and C-17) are just as active and in some cases more active than the natural products. Analogues with the natural R configuration at C-10 and the unnatural R configuration at C-4 are most potent. Replacing the natural propionamide N-terminus cap with the more sterically hindered pivaloylamide N-terminus cap leads to enhanced potency. The tetramic acid fragment and the methyl ether on the tetramic acid fragment are essential for activity. The SAR optimized analogue 76 is more selective, easier to synthesize, more potent, and presumed to be more resistant to proteolysis than the natural sintokamides.

5.
iScience ; 23(8): 101433, 2020 Aug 21.
Artículo en Inglés | MEDLINE | ID: mdl-32823063

RESUMEN

The anti-inflammatory actions of interleukin-10 (IL10) are thought to be mediated primarily by the STAT3 transcription factor, but pro-inflammatory cytokines such as interleukin-6 (IL6) also act through STAT3. We now report that IL10, but not IL6 signaling, induces formation of a complex between STAT3 and the inositol polyphosphate-5-phosphatase SHIP1 in macrophages. Both SHIP1 and STAT3 translocate to the nucleus in macrophages. Remarkably, sesquiterpenes of the Pelorol family, which we previously described as allosteric activators of SHIP1 phosphatase activity, could induce SHIP1/STAT3 complex formation in cells and mimic the anti-inflammatory action of IL10 in a mouse model of colitis. Using crystallography and docking studies we identified a drug-binding pocket in SHIP1. Our studies reveal new mechanisms of action for both STAT3 and SHIP1 and provide a rationale for use of allosteric SHIP1-activating compounds, which mimic the beneficial anti-inflammatory actions of IL10. VIDEO ABSTRACT.

6.
Mol Oncol ; 14(10): 2455-2470, 2020 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-32734688

RESUMEN

Resistance of castration-resistant prostate cancer (CRPC) to enzalutamide and abiraterone involves the expression of constitutively active, truncated androgen receptor (AR) splice variants (AR-Vs) that lack a C-terminal ligand-binding domain (LBD). Both full-length AR and truncated AR-Vs require a functional N-terminal domain (NTD) for transcriptional activity thereby providing rationale for the development of ralaniten (EPI-002) as a first-in-class antagonist of the AR-NTD. Here, we evaluated the antitumor effect of a next-generation analog of ralaniten (EPI-7170) as a monotherapy or in combination with enzalutamide in prostate cancer cells that express AR-V7 that were resistant to enzalutamide. EPI-7170 had 8-9 times improved potency compared to ralaniten. Enzalutamide increased levels of AR-V7 and expression of its target genes. Knockdown of AR-V7 restored sensitivity to enzalutamide, indicating a role for AR-V7 in the mechanism of resistance. EPI-7170 inhibited expression of genes transcriptionally regulated by full-length AR and AR-V7. A combination of EPI-7170 and enzalutamide resulted in synergistic inhibition of proliferation of enzalutamide-resistant cells that was consistent with results from cell cycle and clonogenic assays. In addition, this drug enhanced the antitumor effect of enzalutamide in enzalutamide-resistant CRPC preclinical models. Thus, a combination therapy targeting both the NTD and LBD of AR, and thereby blocking both full-length AR and AR-Vs, has potential for the treatment of enzalutamide-resistant CRPC.

7.
Molecules ; 25(12)2020 Jun 24.
Artículo en Inglés | MEDLINE | ID: mdl-32599753

RESUMEN

The increasing prevalence of drug-resistant influenza viruses emphasizes the need for new antiviral countermeasures. The M2 protein of influenza A is a proton-gated, proton-selective ion channel, which is essential for influenza replication and an established antiviral target. However, all currently circulating influenza A virus strains are now resistant to licensed M2-targeting adamantane drugs, primarily due to the widespread prevalence of an M2 variant encoding a serine to asparagine 31 mutation (S31N). To identify new chemical leads that may target M2(S31N), we performed a virtual screen of molecules from two natural product libraries and identified chebulagic acid as a candidate M2(S31N) inhibitor and influenza antiviral. Chebulagic acid selectively restores growth of M2(S31N)-expressing yeast. Molecular modeling also suggests that chebulagic acid hydrolysis fragments preferentially interact with the highly-conserved histidine residue within the pore of M2(S31N) but not adamantane-sensitive M2(S31). In contrast, chebulagic acid inhibits in vitro influenza A replication regardless of M2 sequence, suggesting that it also acts on other influenza targets. Taken together, results implicate chebulagic acid and/or its hydrolysis fragments as new chemical leads for M2(S31N) and influenza-directed antiviral development.

8.
Cancers (Basel) ; 12(7)2020 Jul 21.
Artículo en Inglés | MEDLINE | ID: mdl-32708219

RESUMEN

Blocking androgen receptor (AR) transcriptional activity by androgen deprivation therapy (ADT) improves the response to radiotherapy for intermediate and high risk prostate cancer. Unfortunately, ADT, antiandrogens, and abiraterone increase expression of constitutively active splice variants of AR (AR-Vs) which regulate DNA damage repair leading to resistance to radiotherapy. Here we investigate whether blocking the transcriptional activities of full-length AR and AR-Vs with ralaniten leads to enhanced sensitivity to radiotherapy. Combination therapies using ralaniten with ionizing radiation were evaluated for effects on proliferation, colony formation, cell cycle, DNA damage, and Western blot analyses in human prostate cancer cells that express both full-length AR and AR-Vs. Ralaniten and a potent next-generation analog (EPI-7170) decreased expression of DNA repair genes whereas enzalutamide had no effect. FACS analysis revealed a dose-dependent decrease of BrdU incorporation with increased accumulation of γH2AX with a combination of ionizing radiation with ralaniten. An additive inhibitory effect on proliferation of enzalutamide-resistant cells was achieved with a combination of ralaniten compounds with ionizing radiation. Ralaniten and EPI-7170 sensitized prostate cancer cells that express full-length AR and AR-Vs to radiotherapy whereas enzalutamide had no added benefit.

9.
Phytochemistry ; 177: 112439, 2020 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-32562917

RESUMEN

Three undescribed spirosteroids, asparacemosones A-C, an undescribed spiro-21-norsteroid, asparacemosone D, along with seven known compounds were isolated from Thai herbal plant Asparagus racemosus Willd. roots. Their structures were elucidated by spectroscopic analysis including NMR, UV, IR and mass spectrometry. The absolute configurations of asparacemosones A, B, and D were determined by single crystal X-ray diffraction using CuKα radiation. Among the isolated compounds, the norlignan nyasol and three acetylenic norlignans demonstrated potent α-glucosidase inhibition, with IC50 values ranging from 0.003 to 0.004 µM which is 5 × 104 fold more potent than the standard acarbose.


Asunto(s)
Asparagus (Planta) , alfa-Glucosidasas , Extractos Vegetales , Raíces de Plantas
10.
J Antibiot (Tokyo) ; 73(8): 568-573, 2020 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-32404991

RESUMEN

Crude extracts of the marine sponge Chelonaplysilla sp. collected in Samoa, that were obtained from the NCI Open Repository (NCS 21903), inhibited Mycobacterium tuberculosis growth. Assay-guided fractionation of the extract led to the isolation and structural elucidation of the known diterpenoid macfarlandin D (1) and three new diterpenoids macfarlandins F (2), G (3), and H (4). Macfarlandin D (1) exhibited potent antimicrobial activity against M. tuberculosis with an MIC of 1.2 ± 0.4 µg mL-1. Macfarlandins F (2), G (3), and H (4) exhibited significantly weaker antitubercular activities, revealing SAR for the macfarlandin antitubercular pharmacophore. The structures of compounds 2, 3, and 4 were elucidated via detailed analysis of NMR and MS data.

11.
Org Lett ; 22(11): 4053-4057, 2020 06 05.
Artículo en Inglés | MEDLINE | ID: mdl-32283033

RESUMEN

Methods for the focused isolation of low-abundance natural products with specific chemical substructures could expand known bioactive chemical diversity for drug discovery. Here we report the combined use of genome mining and an 15N NMR-based screening method for the targeted isolation of the low-abundance piperazic-acid-containing peptides incarnatapeptins A (1) and B (3). Incarnatapeptin B (3) shows in vitro cytotoxicity to LNCaP prostate cancer cells.

12.
Bioorg Med Chem ; 28(10): 115462, 2020 05 15.
Artículo en Inglés | MEDLINE | ID: mdl-32247751

RESUMEN

The first phytochemical investigation of Polyalthia cinnamomea led to the isolation and identification of two new oxoprotoberberine alkaloids, (-)-(13aS)-polyalthiacinnamines A and B, together with eleven known compounds. The structures of the new compounds were elucidated by extensive spectroscopic methods. The absolute configuration of miliusacunine E and consanguine B was established by X-ray diffraction analysis using Cu Kα radiation and ECD spectra, whereas the absolute configurations of polyalthiacinnamines A and B were established by comparison of their ECD spectra and specific rotations with those of miliusacunine E and consanguine B. Compounds 1-4, 6, and 8 exhibited α-glucosidase inhibitory activities (IC50 values ranging from 11.3 to 57.9 µM) better than a positive control (acarbose, IC50 83.5 µM). Compound 2 also exhibited NO production inhibitory activity with an IC50 value of 24.4 µM (indomethacin, a positive control, IC50 = 32.2 µM).

13.
ACS Omega ; 5(7): 3661-3669, 2020 Feb 25.
Artículo en Inglés | MEDLINE | ID: mdl-32118181

RESUMEN

4-N,N-Dimethylamino-1,8-naphthalimide conjugate of trehalose (DMN-Tre) is a fluorogenic dye recently developed as a diagnostic tool for tuberculosis. DMN-Tre selectively labels the mycobacterial cell wall through the Ag85 enzymes. In this work, we disclose a protocol describing the total synthesis of DMN-Tre with more than 99% purity. We further developed a protocol for in vitro and intercellular labeling of various mycobacterial strains. DMN-Tre labeling was found to be a useful tool to study in vitro and intracellular Mycobacterium tuberculosis (Mtb) physiology and as an end-point readout system in high-content image-based screening (HCS) of drug molecules. Such uses of DMN-Tre labeling provide a simple, fast, and cheap alternative to the existing, time-consuming approach that requires Mtb strains to be genetically transformed with fluorescent reporter genes.

14.
Phytochemistry ; 171: 112248, 2020 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-31918304

RESUMEN

The phytochemical investigation of the twig and leaf extracts of Goniothalamus tamirensis led to the isolation and identification of 15 compounds including three rare previously undescribed styryllactones, goniotamirenones A-C, together with 12 known compounds. (Z)-6-Styryl-5,6-dihydro-2-pyranone and 5-(1-hydroxy-3-phenyl-allyl)-dihydro-furan-2-one are reported here for the first time as previously undescribed natural products. Their structures were elucidated by spectroscopic methods. Goniotamirenone A was synthesized via a [2 + 2] cycloaddition reaction of 6-styrrylpyran-2-one in quantitative yield. The absolute configurations of goniotamirenones B and C were identified from experimental and calculated ECD data, while the absolute configurations of (-)-5-acetoxygoniothalamin, (-)-isoaltholactone, parvistone E, and 5-(1-hydroxy-3-phenyl-allyl)-dihydro-furan-2-one were identified by single-crystal X-ray diffraction analysis using Cu Kα radiation. The absolute configurations of the other related compounds were determined from comparisons of their ECD spectra with relevant compounds reported in the literature. (-)-5-Acetoxygoniothalamin exhibited potent cytotoxicity against the colon cancer cell line (HCT116) with an IC50 value of 8.6 µM which was better than the standard control (doxorubicin, IC50 = 9.7 µM), while (Z)-6-styryl-5,6-dihydro-2-pyranone was less active with an IC50 value of 22.1 µM.


Asunto(s)
Antineoplásicos Fitogénicos/farmacología , Goniothalamus/química , Lactonas/farmacología , Fitoquímicos/farmacología , Extractos Vegetales/farmacología , Estirenos/farmacología , Antineoplásicos Fitogénicos/química , Antineoplásicos Fitogénicos/aislamiento & purificación , Proliferación Celular/efectos de los fármacos , Cristalografía por Rayos X , Teoría Funcional de la Densidad , Ensayos de Selección de Medicamentos Antitumorales , Células HCT116 , Humanos , Lactonas/química , Lactonas/aislamiento & purificación , Modelos Moleculares , Estructura Molecular , Fitoquímicos/química , Fitoquímicos/aislamiento & purificación , Extractos Vegetales/química , Extractos Vegetales/aislamiento & purificación , Estirenos/química , Estirenos/aislamiento & purificación
15.
J Nat Prod ; 83(1): 164-168, 2020 01 24.
Artículo en Inglés | MEDLINE | ID: mdl-31860303

RESUMEN

Five new compounds-two phloroglucinol benzophenones, garciniacowones F (1) and G (2), and three xanthones, garciniacowones H (3), I (4), and J (5)-together with seven known xanthones (6-12) were isolated from the fresh leaves of Garcinia cowa. Their structures were elucidated by detailed analysis of NMR and MS data. Compounds 1 and 2 are phloroglucinol benzophenones containing a polyprenylated bicyclo[3.3.1]nonane ring system, while compounds 3-5 are rare xanthones having farnesyl (3 and 5) and geranylgeranyl (5) units at C-8. Compounds 1, 3, 4, 7, 8, and 10 exhibited inhibitory effects on NO production in LPS-induced RAW264.7 macrophage cells with IC50 values ranging from 5.4 to 18.6 µM. Compounds 4 and 8 had α-glucosidase inhibitory activities with IC50 values of 15.4 and 11.4 µM, respectively, which were more potent than that of the acarbose control.

16.
Nat Prod Rep ; 37(5): 617-633, 2020 05 01.
Artículo en Inglés | MEDLINE | ID: mdl-31750842

RESUMEN

Covering: 2000 to 2019The discovery of new natural products that have some combination of unprecedented chemical structures, biological activities of therapeutic interest for urgent medical needs, and new molecular targets provides the fuel that sustains the vitality of natural products chemistry research. Unfortunately, finding these important new compounds is neither routine or trivial and a major challenge is finding effective discovery paradigms. This review presents examples that illustrate the effectiveness of a chemical genetics approach to marine natural product (MNP) discovery that intertwines compound discovery, molecular target identification, and phenotypic response/biological activity. The examples include MNPs that have complex unprecedented structures, new or understudied molecular targets, and potent biological activities of therapeutic interest. A variety of methods to identify molecular targets are also featured.

17.
Pest Manag Sci ; 76(4): 1541-1548, 2020 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-31696600

RESUMEN

BACKGROUND: Larvae of the diamond back moth (DBM), Plutella xylostella, are destructive cabbage pests causing economic losses worldwide. Continuous application of synthetic pesticides to control this pest has resulted in environmental pollution and resistant pest strains. Thus, there is a crucial need to seek natural alternatives with minimal detrimental effects. This study was designed to investigate the antifeedant activities of endophytic fungi of Cyperus iria and to determine the antifeedant, contact toxicity and oviposition deterrent activities of phyllostine acetate and phyllostine of the endophytic Diaporthe miriciae fungus. RESULTS: Two cyclohexeneoxidediones, phyllostine acetate (1) and phyllostine (2), isolated from an ethyl acetate extract of D. miriciae exhibited strong antifeedant, contact toxicity, and oviposition deterrent activities against P. xylostella. Phyllostine acetate (1) and phyllostine (2) showed feeding deterrent indexes of 100% at 50 µg cm-2 in the no-choice leaf disc assay and 50% feeding deterrence (DC50 ) values of 9 and 4.7 µg cm-2 respectively. The median lethal concentration (LC50 ) values of phyllostine acetate (1) and phyllostine (2) were 4.38 and 6.54 µg/larva in the contact toxicity assay. The oviposition deterrent indexes of the two compounds were 100% for phyllostine acetate (1) and 28.6% for phyllostine (2) at 50 µg cm-2 . CONCLUSION: Phyllostine acetate and phyllostine show promise as compounds for the control of P. xylostella. This study encourages further investigation of endophytic fungi of the family Cyperacea, for the development of natural pest control agents in agriculture. © 2019 Society of Chemical Industry.


Asunto(s)
Mariposas Nocturnas , Oviposición , Acetatos , Animales , Femenino , Hongos , Gentisatos , Larva
18.
J Nat Prod ; 82(11): 3176-3180, 2019 11 22.
Artículo en Inglés | MEDLINE | ID: mdl-31661271

RESUMEN

Five new aristolactam alkaloids (1-5), dasymaschalolactams A-E, and the first isolation of dasymaschalolactone (17) as a natural product, together with 19 known compounds (6-16 and 18-25) were isolated from the twig extract of Dasymaschalon dasymaschalum. Their structures were elucidated by spectroscopic methods as well as comparisons made from the literature. Compounds 20 and 21 showed α-glucosidase inhibitory activities with IC50 values of 4.5 and 24.7 µM, respectively.


Asunto(s)
Annonaceae/química , Inhibidores Enzimáticos/química , Inhibidores Enzimáticos/farmacología , Inhibidores de Glicósido Hidrolasas/química , Inhibidores de Glicósido Hidrolasas/farmacología , Hipoglucemiantes/síntesis química , Hipoglucemiantes/farmacología , Lactamas/química , Lactamas/farmacología , Extractos Vegetales/química , Extractos Vegetales/farmacología , Tallos de la Planta/química
19.
J Nat Prod ; 82(8): 2343-2348, 2019 08 23.
Artículo en Inglés | MEDLINE | ID: mdl-31403786

RESUMEN

A chemical investigation of leaf and root extracts of Millettia extensa led to the isolation and structural elucidation of four new prenylated isoflavones, millexatins G-J (1-4), and three new coumaronochromones, millexatins K-M (5-7), along with 16 known compounds. The structures of the new compounds were determined on the basis of NMR and MS data. Compound 4 is a rare isoflavone having a 2-hydroxyethyl moiety at C-8, whereas the structures of compounds 5-7 formally arise from a ring closure through HO-2' and C-2. The absolute configurations at the C-2 and C-3 positions of 5 and 6 were determined from their ECD spectra through comparison with those of previously reported compounds. Most of compounds were evaluated for their inhibitory effects against nitric oxide (NO) production on RAW264.7 macrophages and their antibacterial activities. Compounds 18 and 19 inhibited NO production with IC50 values of 8.5 and 14.3 µM, respectively. Compounds 13 and 14 showed antibacterial activity against various Gram-positive bacteria with MIC values ranging from 2 to 8 µg/mL.


Asunto(s)
Antibacterianos/farmacología , Cromonas/farmacología , Isoflavonas/farmacología , Millettia/química , Óxido Nítrico/antagonistas & inhibidores , Animales , Isoflavonas/química , Ratones , Pruebas de Sensibilidad Microbiana , Óxido Nítrico/biosíntesis , Prenilación , Células RAW 264.7
20.
Fitoterapia ; 138: 104340, 2019 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-31465816

RESUMEN

The first phytochemical investigation of Uvaria lurida resulted in the isolation and identification of three new polyoxygenated cyclohexenes, (+)-(1R,2S,3R,6S)-uvarialuridols A-C (1-3), together with 10 known compounds (4-13). All new structures were elucidated by spectroscopic methods and HRESIMS. The absolute configurations of compounds 1 and 5 were confirmed by X-ray diffraction analysis using Cu Kα radiation. The absolute configurations of compounds 2-4 were identified from comparisons of their specific rotations and ECD spectra with those of known compounds. Compound 11 showed α-glucosidase inhibitory activity with an IC50 value of 30 µM which was better than the standard control, acarbose (74 µM) whereas, compound 10 exhibited nitric oxide (NO) production inhibitory activity with an IC50 value of 37 µM.


Asunto(s)
Ciclohexenos/farmacología , Uvaria/química , Animales , China , Ciclohexenos/aislamiento & purificación , Inhibidores de Glicósido Hidrolasas/aislamiento & purificación , Inhibidores de Glicósido Hidrolasas/farmacología , Ratones , Estructura Molecular , Óxido Nítrico/metabolismo , Fitoquímicos/aislamiento & purificación , Fitoquímicos/farmacología , Extractos Vegetales/química , Hojas de la Planta/química , Células RAW 264.7
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA
...