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1.
Sci Rep ; 14(1): 20677, 2024 09 05.
Artículo en Inglés | MEDLINE | ID: mdl-39237741

RESUMEN

Mosquito-borne diseases, such as malaria, dengue, and Zika, pose major public health challenges globally, affecting millions of people. The growing resistance of mosquito populations to synthetic insecticides underscores the critical need for effective and environmentally friendly larvicides. Although chemical pesticides can initially be effective, they often lead to negative environmental consequences and health hazards for non-target species, including humans. This study aimed to evaluate the larvicidal effects of Trachyspermum ammi essential oil and Delphinium speciosum extract on the larvae of three major mosquito species: Aedes aegypti, Anopheles stephensi, and Culex quinquefasciatus. Mosquito larvae of Ae. aegypti, An. stephensi, and Cx. quinquefasciatus were reared under controlled laboratory conditions. The larvicidal activity of T. ammi essential oil and D. speciosum extract was evaluated through standard bioassays, using various concentrations of essential oils (10, 20, 40, 80, and 160 ppm) and extracts (160, 320, 640, 1280, and 2560 ppm) to determine the lethal concentration (LC50) values after 24 h of exposure. Fresh plant materials were collected, with the essential oil extracted via hydro-distillation, and the extract prepared using methanol solvent extraction. The chemical composition of T. ammi essential oil was examined using gas chromatography-mass spectrometry (GC-MS). Additionally, the preliminary analysis of the chemical compounds in D. speciosum extract was carried out using thin layer chromatography (TLC) and nuclear magnetic resonance spectroscopy (NMR) techniques. The results indicated that the essential oil of T. ammi exhibited more effective larvicidal activity compared to the D. speciosum extract. Specifically, the essential oil demonstrated LC50 values of 18 ppm for Cx. quinquefasciatus and 19 ppm for Ae. aegypti. In contrast, the D. speciosum extract showed the strongest larvicidal effect against An. stephensi, with an LC50 of 517 ppm. Concentrations of 40 ppm of the essential oil and 1280 ppm of the extract resulted in 100% mortality across all three species. Both the essential oil of T. ammi and the D. speciosum extract exhibited concentration-dependent larvicidal activity, and these results were statistically significant (p < 0.001) compared to the no-treatment group. GC-MS analysis revealed thymol (88.95%), o-cymen-5-ol (4.11%), and γ-terpinene (2.10%) as the major constituents of the T. ammi essential oil. Additionally, TLC verified the presence of alkaloids in both chloroform and methanolic extracts. Proton NMR identified a diterpene structure for these alkaloids. These findings suggest that T. ammi essential oil is a promising candidate for natural mosquito control strategies. Given its efficacy, further research is warranted to explore its potential in integrated vector management programs.


Asunto(s)
Delphinium , Insecticidas , Larva , Mosquitos Vectores , Aceites Volátiles , Extractos Vegetales , Animales , Aceites Volátiles/farmacología , Aceites Volátiles/química , Larva/efectos de los fármacos , Mosquitos Vectores/efectos de los fármacos , Extractos Vegetales/farmacología , Extractos Vegetales/química , Insecticidas/farmacología , Insecticidas/química , Delphinium/química , Aedes/efectos de los fármacos , Dengue , Malaria/prevención & control , Anopheles/efectos de los fármacos , Filariasis , Culex/efectos de los fármacos , Control de Mosquitos/métodos
2.
Phytochemistry ; 225: 114186, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38878944

RESUMEN

The ethanol extract of the whole plant of Delphinium trichophorum Franch was subjected to a phytochemical study, leading to the isolation of ten unprecedented diterpenoid alkaloids, including nine delnudine-type C20-diterpenoid alkaloids named trichophodines A-I and one kusnezoline-type C20-diterpenoid alkaloid named trichophozine A. Additionally, seven known compounds were also identified. Their structures were elucidated on the basis of extensive spectroscopic analysis, including HSQC, HMBC, 1H-1H COSY, NOESY and X-ray crystallographic analysis. Most isolated compounds were screened for inhibitory activities against LPS-induced NO production in RAW 264.7 macrophage cells and acetylcholinesterase inhibitory effects. Guan-fu base V exhibited potent inhibitory activity against acetylcholinesterase, demonstrating an inhibitory rate of 53.81% at a concentration of 40 µM.


Asunto(s)
Alcaloides , Inhibidores de la Colinesterasa , Delphinium , Diterpenos , Delphinium/química , Ratones , Diterpenos/química , Diterpenos/farmacología , Diterpenos/aislamiento & purificación , Animales , Células RAW 264.7 , Alcaloides/química , Alcaloides/farmacología , Alcaloides/aislamiento & purificación , Estructura Molecular , Inhibidores de la Colinesterasa/farmacología , Inhibidores de la Colinesterasa/química , Inhibidores de la Colinesterasa/aislamiento & purificación , Lipopolisacáridos/farmacología , Lipopolisacáridos/antagonistas & inhibidores , Óxido Nítrico/antagonistas & inhibidores , Óxido Nítrico/biosíntesis , Acetilcolinesterasa/metabolismo , Acetilcolinesterasa/efectos de los fármacos , Relación Estructura-Actividad , Relación Dosis-Respuesta a Droga
3.
Bioorg Chem ; 148: 107478, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38788366

RESUMEN

The current standard treatment for ovarian cancer consists of surgery to reduce the size of the tumor, followed by treatment with chemotherapeutic drugs, which have major side effects. Therefore, finding a new natural product drug with fewer side effects is a strategy. Delphinium brunonianum (D. brunonianum) is a traditional Tibetan medicine, mainly from southern Tibet, China, whereas the chemical constituents in this plant remain elusive. The major metabolites in the dichloromethane fraction of D. brunonianum were analyzed and purified by HPLC and various column chromatography techniques. Nine diterpenoid alkaloids (1-9) and one amide alkaloid (10) were isolated from D. brunonianum, including three novel C19-type diterpenoid alkaloids (Brunonianines D-F) (1-3). Their structures were elucidated by 1D/2D NMR, HR-ESI-MS and single-crystal X-ray diffraction analyses. All compounds were evaluated for toxicity in four tumor cell lines. Most of the compounds exhibited potent inhibitory effects on Skov-3 cell lines, with IC50 values ranging from 2.57 to 8.05 µM. The western blotting experiment was used to further analyze the expression levels of molecules in the Bax/Bcl-2/Caspase-3 signaling pathway for compound 1. Molecular docking was performed to predict the binding modes of Brunonianine D with target proteins. In vivo experiments were also performed and evaluated in real time by monitoring the size of the Skov-3 tumor. Additionally, tumor H&E staining and the TUNEL assay used to evaluate anti-tumor effects.


Asunto(s)
Alcaloides , Antineoplásicos Fitogénicos , Apoptosis , Proliferación Celular , Delphinium , Diterpenos , Ensayos de Selección de Medicamentos Antitumorales , Neoplasias Ováricas , Femenino , Humanos , Delphinium/química , Alcaloides/farmacología , Alcaloides/química , Alcaloides/aislamiento & purificación , Antineoplásicos Fitogénicos/farmacología , Antineoplásicos Fitogénicos/química , Antineoplásicos Fitogénicos/aislamiento & purificación , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/patología , Relación Estructura-Actividad , Animales , Estructura Molecular , Diterpenos/farmacología , Diterpenos/química , Diterpenos/aislamiento & purificación , Proliferación Celular/efectos de los fármacos , Apoptosis/efectos de los fármacos , Ratones , Relación Dosis-Respuesta a Droga , Línea Celular Tumoral , Simulación del Acoplamiento Molecular
4.
Daru ; 32(1): 237-251, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38498253

RESUMEN

BACKGROUND: The cholinergic hypothesis posits a robust correlation between the onset of Alzheimer's disease and a pronounced deficit in acetylcholine, a pivotal neurotransmitter crucial for the central cholinergic nervous system's function, pivotal for memory and learning. Diterpene alkaloids exhibit intricate and distinctive chemical structures that facilitate their passage through the blood-brain barrier. Moreover, their potent pharmacological attributes render them promising candidates for addressing central nervous system disorders. OBJECTIVES: This investigation aims to scrutinize the alkaloidal composition of Delphinium cyphoplectrum (Ranunculaceae) roots, further exploring their anticholinesterase inhibitory activity and mode of inhibition. METHOD: Innovative chromatography techniques were repetitively employed to purify the alkaloids. Acetylcholinesterase (AChE) inhibition assays were conducted using Ellman's tests. The mode of inhibition was meticulously characterized through Michaelis-Menten, and Lineweaver-Burk plots. Conducting molecular docking studies, we employed the AUTO DOCK 4.2 software package. RESULTS: Eight alkaloids were identified including five C19-diterpene alkaloids (6,14,16,18-tetramethoxy-1,7,8-trihydroxy-4-methylaconitane (1), 6,16,18-trimethoxy-1,7,8,14-tetrahydroxy-4-methylaconitane (2), 6,8,16,18-tetramethoxy-1,7,14-trihydroxy-4-methylaconitane (3), 6,14,16-trimethoxy-1,7,8,18-tetrahydroxy-4-methylaconitane (4), and 14-O-acetyl-8,16-dimethoxy-1,6,7,18-tetrahydroxy-4-methylaconitane (5)), an epoxy C18-diterpene alkaloid (6,8,16-trimethoxy-1,7,14-trihydroxy-3,4-epoxyaconitane (6)), a known (pyrrolidin-2-one (7) and an undescribed amide alkaloid (1-(2'-hydroxylethylamine)-3,5,5,-trimethyl-1,5-dihydro-2H-pyrrol-2-one (8). All diterpene alkaloids underwent assessment for acetylcholinesterase (AChE) inhibition assay and displayed noteworthy AChE activity, surpassing that of the reference drug (with IC50 values of 13.7, 21.8, 23.4, 28.2, 40.4, and 23.9 for compounds 1-6, respectively, in comparison to 98.4 for Rivastigmine). Analysis of Michaelis-Menten and Lineweaver-Burk plots represents an uncompetitive mode of inhibition for compound 1 on AChE. Notably, computational docking simulations indicated that all diterpene alkaloids were accommodated within the same enzymatic cleft as the reference ligand, and displaying superior free binding energy values (from - 10.32 to -8.59 Kcal.mol-1) in contrast to Rivastigmine (-6.31 Kcal.mol-1). CONCLUSION: The phytochemical analysis conducted on the roots of Delphinium cyphoplectrum yielded the identification of eight alkaloidal compounds including one C18-diterpene, five C19-diterpene, one pyrrolidine and one amide alkaloids. AChE inhibition assay and molecular simulations unveiled remarkable significant potency attributed to the C19-diterpene alkaloids by the order of 1 > 2 > 3,6 > 4 > 5. Presence of hydroxyl group on C-1, C-7, C-8, C-14, and C-18 increased the effect. The best in vitro activity was recorded for compound 1 able to bind to Asp72 in the narrow region of PAS, while interacting by pi-sigma with Phe330 at the hydrophobic region of the gorge involving the acyl and choline binding site. This observation underscores the substantial promise of this category of natural products in the realm of drug discovery for Alzheimer's Disease, offering a compelling avenue for further research and therapeutic development.


Asunto(s)
Inhibidores de la Colinesterasa , Delphinium , Simulación del Acoplamiento Molecular , Raíces de Plantas , Inhibidores de la Colinesterasa/farmacología , Inhibidores de la Colinesterasa/química , Delphinium/química , Raíces de Plantas/química , Alcaloides Diterpénicos/química , Acetilcolinesterasa/química , Acetilcolinesterasa/metabolismo , Extractos Vegetales/química , Extractos Vegetales/farmacología , Alcaloides/química , Alcaloides/farmacología , Alcaloides/aislamiento & purificación , Animales , Diterpenos/química , Diterpenos/farmacología , Diterpenos/aislamiento & purificación
5.
Phytochemistry ; 219: 113987, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38218306

RESUMEN

Cyano tends to have better biological activity, but it is rarely reported in natural products, especially in the C20-diterpene alkaloids. Herein, three unprecedented C20-diterpenoid alkaloids, brunonianines A-C (1-3), possessing rare cyano functional group as well as an atisine backbone constructed from a phenethyl substituent and a tetrahydropyran ring, along with four C19-alkaloids (4-7) and one amide alkaloids (8), were isolated from the whole plant of Delphinium brunonianum Royle. Compounds 1-3 are also the first atisine type diterpenoid alkaloids with cyano group obtained from nature. The structures of the previously undescribed compounds were elucidated by HR-ESI-MS, 1D/2D NMR spectroscopic data and electronic circular dichroism calculations and single-crystal X-ray diffraction. Reasonable speculations have also been made regarding the biogenic synthetic pathways of compounds 1-3. In addition, the inhibitory activity of all compounds was also tested against four tumor lines: A549, Caco-2, H460 and Skov-3, where compound 2 (IC50 2.20 ± 0.21 µM) showed better inhibitory activity against Skov-3 cells than the hydroxycamptothecin. Using flow cytometry, cell staining, migration and invasion analysis, and Western blot, compound 2 was found to arrest cells in the G2/M phase and was able to effectively inhibit cell motility to achieve potent anti-tumor effects. In addition, compound 2 can effectively induce apoptosis by activating the Bax/Bcl-2/Caspase-3 signaling pathway.


Asunto(s)
Alcaloides , Delphinium , Diterpenos , Humanos , Delphinium/química , Estructura Molecular , Células CACO-2 , Alcaloides/farmacología , Alcaloides/química , Diterpenos/farmacología , Diterpenos/química
6.
Chem Biodivers ; 21(6): e202301923, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38191840

RESUMEN

Two new C19-diterpenoid alkaloids of the lycoctonine-type (liangshanine A and liangshanine B) and nineteen known compounds (3-21) were isolated from the whole plant of Delphinium liangshanense W. T. Wang, and all the compounds were identified by different spectroscopic analyses, such as IR, HR-ESI-MS and NMR. All the compounds were isolated from this plant for the first time and tested for the anti-proliferation effects on MH7 A and SF9 cells to figure their anti-rheumatoid arthritis and anti-insect activity, but none of them showed remarkable activity.


Asunto(s)
Alcaloides , Delphinium , Diterpenos , Delphinium/química , Diterpenos/química , Diterpenos/aislamiento & purificación , Diterpenos/farmacología , Alcaloides/química , Alcaloides/aislamiento & purificación , Alcaloides/farmacología , Animales , Proliferación Celular/efectos de los fármacos , Línea Celular , Spodoptera/efectos de los fármacos , Estructura Molecular , Humanos , Conformación Molecular
7.
Chem Biodivers ; 21(2): e202301958, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38130145

RESUMEN

Three novel diterpenoid alkaloids, comprising two C19 -diterpenoid alkaloids (1 and 2) and one C20 -diterpenoid alkaloid (3), were isolated from Delphinium ajacis, alongside the six known compounds (4-9). Their structures were elucidated by spectroscopic methods (MS, UV, IR, 1D and 2D NMR) and chemical properties. Simultaneously, the anti-inflammatory properties of all compounds (1-9) was conducted, focusing on nitric oxide (NO) production in LPS-induced BV-2 cells. The results indicated compounds 1-3, 7, and 8 have potential anti-inflammatory activity.


Asunto(s)
Alcaloides , Delphinium , Diterpenos , Delphinium/química , Espectroscopía de Resonancia Magnética , Alcaloides/farmacología , Alcaloides/química , Diterpenos/farmacología , Diterpenos/química , Antiinflamatorios/farmacología , Estructura Molecular
8.
Phytochemistry ; 215: 113822, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37574118

RESUMEN

Delphinium kamaonense Huth is a sort of folkloric plant resource which is cultivated and planted with great ornamental and medicinal values. In this work, seven undescribed lycaconitine-type C19-diterpenoid alkaloids, especially a rare skeleton with -CH=N and N-oxide moieties, along with ten known compounds, were isolated from D. kamaonense, of which the structures were determined by various spectroscopic data, combined with calculated electronic circular dichroism (ECD) and single-crystal X-ray diffraction analysis. In vitro nitric oxide inhibitory activities assay of these compounds indicated that lycaconitine-type C19-diterpenoid alkaloids had significant anti-inflammatory inhibitory activities, with kamaonensine E being the most potent (0.9 ± 0.2 µM) stronger than positive (9.0 ± 1.3 µM). In the network pharmacology studies, binding three key targets mitogen-activated protein kinase 8 (MAPK8), mitogen-activated protein kinase 14 (MAPK14), and heat shock protein HSP 90-alpha (HSP90α), the anti-inflammatory mechanism might be related to MAPK signaling pathways. Furthermore, the molecular docking results revealed that the uncommon amides and methylenedioxy groups might be the most two promising pharmacophores for lycaconitine-type C19-diterpenoid alkaloids.


Asunto(s)
Alcaloides , Delphinium , Diterpenos , Delphinium/química , Simulación del Acoplamiento Molecular , Alcaloides/química , Diterpenos/química , Dicroismo Circular , Estructura Molecular
9.
J Asian Nat Prod Res ; 25(12): 1175-1183, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37218665

RESUMEN

Three new hetisine type C20-diterpenoid alkaloids, named as trichophorines A-C (1-3), were isolated from Delphinium trichophorum, together with nine known alkaloids (4-12). Their structures were elucidated on the basis of spectroscopic data (1D, 2D NMR, single-crystal X-ray, and HR-ESI-MS). All compounds were evaluated for the inhibitory activities against LPS induced NO production in RAW 264.7 macrophage cells, and none of them showed considerable inhibitory activity.


Asunto(s)
Alcaloides , Delphinium , Diterpenos , Delphinium/química , Espectroscopía de Resonancia Magnética , Alcaloides/farmacología , Alcaloides/química , Diterpenos/farmacología , Diterpenos/química , Estructura Molecular
10.
Chem Biodivers ; 20(3): e202200936, 2023 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-36696143

RESUMEN

Shawurenine C (1a) and D (1b), a new pair of regioisomeric C19 -diterpenoid alkaloids, and five known C19 -diterpenoid alkaloids (2-6) were isolated from the aerial part of Delphinium shawurense W. T. Wang. The chemical structures of new compounds were established based on spectroscopic analyses: HR-ESI-MS, and 1D, 2D NMR spectroscopic data. The anti-inflammatory and cytotoxic activities of these diterpenoid alkaloids were also evaluated.


Asunto(s)
Alcaloides , Delphinium , Diterpenos , Delphinium/química , Estructura Molecular , Espectroscopía de Resonancia Magnética , Alcaloides/farmacología , Alcaloides/química , Diterpenos/farmacología , Diterpenos/química
11.
Nat Prod Res ; 37(1): 130-135, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-34241556

RESUMEN

A new C19-diterpenoid alkaloid named gyalanutine A (1) and fourteen known compounds 2-15 were isolated from the plant of Delphinium gyalanum C. Marquand & Airy Shaw. Compound 1 displayed an unusual lycoctonine-type C19-diterpenoid alkaloid skeleton with the cleavage of N-C19 and C7-C17 bonds, and the construction of the N-C7 bond. Structures were identified by multiple spectroscopic analyses including 1 D, 2 D NMR, IR and HR-ESI-MS. Compounds were tested for acetylcholinesterase inhibitory and anti-inflammatory activity.


Asunto(s)
Alcaloides , Antineoplásicos , Delphinium , Diterpenos , Delphinium/química , Acetilcolinesterasa , Estructura Molecular , Alcaloides/química , Espectroscopía de Resonancia Magnética , Diterpenos/química
12.
Fitoterapia ; 162: 105268, 2022 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-35963483

RESUMEN

The main objective of our present research work was to explore molecular insight for potentially active new acetylcholinesterase inhibitor from the aerial parts of Delphinium uncinatum. New norditerpenoid alkaloids, uncinatine-A, was isolated from the basic alkaloidal fraction of D. uncinatum, based on bioactivity guided isolation. The structure of uncinatine-A was determined through latest spectroscopic techniques including single X-Ray diffraction technique. The structural data and electronic properties of uncinatine-A was also calculated by Density Functional Theory (DFT) using B3LYP/6-31þ G (p) basis set. The isolated natural product was evaluated for their acetyl cholinesterase inhibitory potential in dose dependent protocol (62.5-1000 µg/mL), followed by molecular docking studies. Significant competitive type inhibition activity (IC50 = 207.73 ± 0.3) was shown by isolated natural norditerpenoid against cholinesterase targets in comparison with standard drugs available in the market such as galanthamine. The molecular docking results showed that isolated natural product was well accommodated by AChE in the active site with docking scores -11.0326. This is the first report indicating uncinatine-A as a potent acetylcholinesterase inhibitor and can be used as a target drug in cerebral dementia and Alzheimer diseases.


Asunto(s)
Alcaloides , Productos Biológicos , Delphinium , Diterpenos , Acetilcolinesterasa/metabolismo , Inhibidores de la Colinesterasa , Delphinium/química , Teoría Funcional de la Densidad , Galantamina , Simulación del Acoplamiento Molecular , Estructura Molecular
13.
Chem Biodivers ; 19(7): e202200463, 2022 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-35785443

RESUMEN

A new amide (1), two new phenylpropanoid derivatives (2, 3), along with three new natural products, including three nitrogen chirality compounds, N-(3-methoxy-1,3-dioxopropyl)-D-phenylalanine methyl ester (4), N-(3-methoxy-1,3-dioxopropyl)-L-phenylalanine methyl ester (5), and N-acetyl-L-phenylalanine methyl ester (6), as well as dimethyl (2R,3R)-2-hydroxy-3-(((E)-3-(4-hydroxyphenyl)acryloyl)oxy)succinate (7) and dimethyl (S,E)-2-((3-(4-hydroxy-3-methoxyphenyl)acryloyl)oxy)succinate (8) were isolated from Delphinium kamaonense Hunth. Their structures were elucidated by extensive analysis of 1D and 2D NMR, and HR-ESI-MS experiments, and the absolute configurations were determined by comparative analysis of specific optical rotation. Compound 1 exhibited a moderate cytotoxicity effect against Hep-3B cancer cell lines (IC50 41.39±0.13 µM) and an excellent antioxidant activity (IC50 0.527±0.06 µM in ABTS assay, and 1.235±0.09 µM in DPPH assay, respectively), which was superior to vitamin C in ABTS (IC50 1.670±0.07 µM) and DPPH (IC50 19.10±0.40 µM) methods.


Asunto(s)
Antineoplásicos , Delphinium , Antineoplásicos/farmacología , Antioxidantes/farmacología , Delphinium/química , Espectroscopía de Resonancia Magnética , Estructura Molecular , Succinatos
14.
Molecules ; 27(14)2022 Jul 07.
Artículo en Inglés | MEDLINE | ID: mdl-35889221

RESUMEN

This study reports the isolation of three new C20 diterpenoid alkaloids, Chitralinine A-C (1-3) from the aerial parts of Delphinium chitralense. Their structures were established on the basis of latest spectral techniques and single crystal X-rays crystallographic studies of chitralinine A described basic skeleton of these compounds. All the isolated Compounds (1-3) showed strong, competitive type inhibition against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) in comparison to standard allanzanthane and galanthamine however, chitralinine-C remained the most potent with IC50 value of 11.64 ± 0.08 µM against AChE, and 24.31 ± 0.33 µM against BChE, respectively. The molecular docking reflected a binding free energy of -16.400 K Cal-mol-1 for chitralinine-C, having strong interactions with active site residues, TYR334, ASP72, SER122, and SER200. The overall findings suggest that these new diterpenoid alkaloids could serve as lead drugs against dementia-related diseases including Alzheimer's disease.


Asunto(s)
Alcaloides , Delphinium , Diterpenos , Acetilcolinesterasa/metabolismo , Alcaloides/química , Butirilcolinesterasa/metabolismo , Inhibidores de la Colinesterasa/química , Delphinium/química , Diterpenos/química , Simulación del Acoplamiento Molecular
15.
J Nat Prod ; 85(4): 1157-1166, 2022 04 22.
Artículo en Inglés | MEDLINE | ID: mdl-35385291

RESUMEN

Thirteen new benzamide alkaloids, delphiniumines A-M (1-13), together with one known analogue (14), were isolated from Delphinium anthriscifolium Hance. All of the structures were determined by spectroscopic and spectrometric analyses. Absolute configuration for 1 was established using experimental and calculated ECD data, as well as by X-ray crystallography analysis. Compound 1 possesses a previously undescribed polysubstituted cyclopentene carbon framework. Compound 2 was isolated as an artifact from 1 during the extraction process. Compound 7 is glycosylated with a ß-D-glucose unit. Compound 13 bears a chlorine substituent. At a concentration of 10 µM, compounds 6, 8, and 10-12 suppressed LPS-induced NO production in RAW264.7 cells with inhibition rates ranging from 40.3% to 78.8%.


Asunto(s)
Alcaloides , Delphinium , Diterpenos , Alcaloides/química , Benzamidas , Ciclopentanos/farmacología , Delphinium/química , Diterpenos/química , Estructura Molecular
16.
Molecules ; 27(7)2022 Mar 30.
Artículo en Inglés | MEDLINE | ID: mdl-35408656

RESUMEN

This research aimed to excavate compounds with activity reducing hepatocytes lipid accumulation from Delphinium brunonianum. Four novel diterpenoid alkaloids, brunodelphinine B-E, were isolated from D. brunonianum together with eleven known diterpenoid alkaloids through a phytochemical investigation. Their structures were elucidated by comprehensive spectroscopy methods including HR-ESI-MS, NMR, IR, UV, CD, and single-crystal X-ray diffraction analysis. The inhibitory effects of a total of 15 diterpenoid alkaloids on hepatocytes lipid accumulation were evaluated using 0.5 mM FFA (oleate/palmitate 2:1 ratio) to induce buffalo rat liver (BRL) cells by measuring the levels of triglyceride (TG), total cholesterol (TC), alanine transaminase (ALT), aspartate transaminase (AST), and the staining of oil red O. The results show that five diterpenoid alkaloids-brunodelphinine E (4), delbruline (5), lycoctonine (7), delbrunine (8), and sharwuphinine A (12)-exhibited significant inhibitory effects on lipid accumulation in a dose-dependent manner and without cytotoxicity. Among them, sharwuphinine A (12) displayed the strongest inhibition of hepatocytes lipid accumulation in vitro. Our research increased the understanding on the chemical composition of D. brunonianum and provided experimental and theoretical evidence for the active ingredients screened from this herbal medicine in the treatment of the diseases related to lipid accumulation, such as non-alcoholic fatty liver disease and hyperlipidemia.


Asunto(s)
Alcaloides , Delphinium , Diterpenos , Alcaloides/química , Alcaloides/farmacología , Delphinium/química , Diterpenos/química , Diterpenos/farmacología , Hepatocitos , Lípidos , Espectroscopía de Resonancia Magnética , Estructura Molecular
17.
Parasitology ; 148(11): 1392-1400, 2021 09.
Artículo en Inglés | MEDLINE | ID: mdl-34162452

RESUMEN

Acanthamoeba spp. are widely distributed in the environment and cause serious infections in humans. Treatment of Acanthamoeba infections is very challenging and not always effective which requires the development of more efficient drugs against Acanthamoeba spp. The purpose of the present study was to test medicinal plants that may be useful in the treatment of Acanthamoeba spp. Here we evaluated the trophozoital and cysticidal activity of 13 flavonoid glycosides isolated from Delphinium gracile, D. staphisagria, Consolida oliveriana and from Aconitum napellus subsp. Lusitanicum against the amoeba Acanthamoeba castellanii. AlamarBlue Assay Reagent® was used to determine the activity against trophozoites of A. castellanii, and cytotoxic using Vero cells. Cysticidal activity was assessed on treated cysts by light microscopy using a Neubauer chamber to quantify cysts and trophozoites. Flavonoids 1, 2, 3 and 4 showed higher trophozoital activity and selectivity indexes than the reference drug chlorhexidine digluconate. In addition, flavonoid 2 showed 100% cysticidal activity at a concentration of 50 µm, lower than those of the reference drug and flavonoid 3 (100 µm). These results suggest that flavonoids 2 and 3 might be used for the development of novel therapeutic approaches against Acanthamoeba infections after satisfactory in vivo evaluations.


Asunto(s)
Acanthamoeba/efectos de los fármacos , Aconitum/química , Delphinium/química , Glicósidos/farmacología , Extractos Vegetales/farmacología , Ranunculaceae/química , Acanthamoeba/crecimiento & desarrollo , Animales , Chlorocebus aethiops , Flavonoides/química , Flavonoides/aislamiento & purificación , Flavonoides/farmacología , Flavonoides/toxicidad , Glicósidos/química , Glicósidos/aislamiento & purificación , Glicósidos/toxicidad , Concentración 50 Inhibidora , Estructura Molecular , Extractos Vegetales/aislamiento & purificación , Trofozoítos/efectos de los fármacos , Trofozoítos/crecimiento & desarrollo , Células Vero/efectos de los fármacos
18.
Molecules ; 26(5)2021 Mar 04.
Artículo en Inglés | MEDLINE | ID: mdl-33806579

RESUMEN

This paper aimed to investigate the potential antifungal influences of new alkaloids from Delphinium peregrinum L. var. eriocarpum Boiss. New Diterpenoid alkaloids Delcarpum (1), Hydrodavisine (4) and known alkaloids Peregrine (2), Delphitisine (3) were isolated by different chromatographic methods from the aerial parts of D. Peregrinum eriocarpum Boiss, which grows in Syria. The structures of alkaloids were proposed based on 1D NMR spectroscopy 1H-NMR, 13C-NMR, DEPT-135, DEPT-90, 2D NMR spectroscopy DQF-COSY, HMQC, EI-Ms mass spectrum, and IR spectroscopic measurements. The antifungal activity of the isolated alkaloids was evaluated against different dermatophyte fungal isolates compared with fluconazole. In the case of Peregrine (2) the minimum inhibitory concentrations(MICs) recorded 128-256, 32-64, and 32 for Epidermophyton floccosum, Microsporum canis, and Trichophyton rubrum, respectively, compared to 32-64, 16, and 32 µg/mL in the case of fluconazole, respectively. The MICs recorded on application of the four alkaloids mixture were 64, 32, and 16 in the case of E. floccosum, M. canis, and T. rubrum, respectively, which were significantly lower than that measured for each of the individual alkaloid and were compatible for fluconazole. In conclusion, MICs of the tested alkaloids showed a variable potential effect on the investigated fungal isolates. Peregrine (2) was the most effective alkaloid, however, the application of the mixture of alkaloids induced significant synergistic activity that was more pronounced than the application of individual ones.


Asunto(s)
Alcaloides/farmacología , Antifúngicos/farmacología , Arthrodermataceae/efectos de los fármacos , Delphinium/química , Diterpenos/farmacología , Epidermophyton/efectos de los fármacos , Extractos Vegetales/farmacología , Alcaloides/aislamiento & purificación , Antifúngicos/aislamiento & purificación , Cromatografía , Diterpenos/aislamiento & purificación , Estructura Molecular , Extractos Vegetales/aislamiento & purificación
19.
Bioorg Med Chem ; 37: 116113, 2021 05 01.
Artículo en Inglés | MEDLINE | ID: mdl-33744825

RESUMEN

Three new diterpenoid alkaloids (1-3), and eight known alkaloids (4-11) were isolated from the aerial parts of Delphinium grandiflorum. Grandifline A (1) represents an unprecedented diterpenoid alkaloid ring system featuring a C-7NC17 hemiaminal moiety and a lactone fragment through the linkage of C-17OC19 unit. And we named this newly-discovered class of rearranged C19-diterpenoid alkaloid scaffold as grandiflodines (B-12). Grandifline B (2) is the first naturally-occurring 7,17-secolycoctonine diterpenoid alkaloid with a C-7OC17 unit forming a hemiacetal. Their structures were elucidated via spectroscopic data and single-crystal X-ray diffraction analysis. The protective effects of compounds 1-11 on H2O2-induced cardiomyocytes injury were assayed. And compounds 6 and 10 showed significant protective effects, with IC50 values of 1.881 ± 0.680 µM and 1.904 ± 0.750 µM, respectively. Further, compound 6 could reduce oxidative damage by inhibiting cell death via the AMPK/AKT/mTOR signaling pathway in H2O2-induced H9C2 cells.


Asunto(s)
Alcaloides/farmacología , Cardiotónicos/farmacología , Delphinium/química , Diterpenos/farmacología , Miocitos Cardíacos/efectos de los fármacos , Alcaloides/química , Alcaloides/aislamiento & purificación , Apoptosis/efectos de los fármacos , Cardiotónicos/química , Cardiotónicos/aislamiento & purificación , Diterpenos/química , Diterpenos/aislamiento & purificación , Peróxido de Hidrógeno/farmacología , Componentes Aéreos de las Plantas/química , Especies Reactivas de Oxígeno/metabolismo
20.
Nat Prod Res ; 35(17): 2982-2986, 2021 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-31674843

RESUMEN

The present study aims at phytochemical profiling and valuating the effect of crude extract of Delphinium brunonianum on fructose mediated rise in blood pressure and metabolic abnormalities in rats. Therefore, rats were fed on fructose (10%w/v) for 6 weeks. Rats in treatment groups received amlodipine 250, 500 and 1000 mg/kg of DB-Cr separately in concurrent to fructose. Various parameters of metabolic perturbations were assessed at the end of study. Further, DB-Cr was analyzed using LC-MS technique. DB-Cr exerted remarkable antihypertensive effect whereas, sympathetic hyperactivity and hyperinsulinemia in these rats was significantly blunted, further, endothelium functionality was successfully restored. LC-MS analysis of DB-Cr revealed the presence of a variety of chemical constituents (41) including quinic acid, scopolin, gingerol, Robinetin 3-rutinoside, KAPA and maleic acid. In conclusion, D. brunonianum possess the potential to combat the fructose mediated hypertension and metabolic perturbations, which may partially be due to its chemical constituents.


Asunto(s)
Delphinium , Hipertensión , Fitoquímicos/farmacología , Extractos Vegetales/farmacología , Animales , Presión Sanguínea , Delphinium/química , Fructosa , Hipertensión/inducido químicamente , Hipertensión/tratamiento farmacológico , Fitoquímicos/química , Ratas
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