RESUMEN
The rising geriatric population is expected to increase the demand for drugs treating neurodegenerative diseases. The present work is aimed to discover acetylcholinesterase (AChE) inhibitors from Cissampelos pareira Linn. aerial parts (Family: Menispermaceae). Bioassay-guided isolation, AChE inhibition study and estimation of the therapeutic marker in different parts of raw herbs were conducted. The structure of the compound (1) was elucidated as N-methylneolitsine by using NMR (1D and 2D) and ESI-MS/MS spectral data, which is a new natural analogue of neolitsine. It showed good AChE inhibition with an IC50 value of 12.32 µg/mL. It was densitometrically estimated to be 0.074 - 0.33% in aerial parts of C. pareira, collected from various locations. The alkaloid reported here could be potentially useful for the treatment of various neurodegenerative diseases and the aerial part of C. pareira could be used as a promising ingredient for various preparations treating neurodegenerative diseases.
Asunto(s)
Cissampelos , Menispermaceae , Enfermedades Neurodegenerativas , Anciano , Humanos , Cissampelos/química , Acetilcolinesterasa , Inhibidores de la Colinesterasa/farmacología , Espectrometría de Masas en Tándem , Extractos Vegetales/farmacología , Extractos Vegetales/química , Componentes Aéreos de las Plantas , BioensayoRESUMEN
Plant-derived medicinal compounds are increasingly being used to treat acute and chronic inflammatory diseases, which are generally caused by aberrant inflammatory responses. Stephania pierrei Diels, also known as Sabu-lueat in Thai, is a traditional medicinal plant that is used as a remedy for several inflammatory disorders. Since aporphine alkaloids isolated from S. pierrei tubers exhibit diverse pharmacological characteristics, we aimed to determine the anti-inflammatory effects of crude extracts and alkaloids isolated from S. pierrei tubers against lipopolysaccharide (LPS)-activated RAW264.7 macrophages. Notably, the n-hexane extract strongly suppressed nitric oxide (NO) while exhibiting reduced cytotoxicity. Among the five alkaloids isolated from the n-hexane extract, the aporphine alkaloid oxocrebanine exerted considerable anti-inflammatory effects by inhibiting NO secretion. Oxocrebanine also significantly suppressed prostaglandin E2, tumour necrosis factor-α, interleukin (IL)-1ß, IL-6, inducible nitric oxide synthase, and cyclooxygenase (COX)-2 protein expression by inactivating the nuclear factor κB, c-Jun NH2-terminal kinase, extracellular signal-regulated kinase 1/2, and phosphatidylinositol 3-kinase/Akt inflammatory signalling pathways. Molecular docking analysis further revealed that oxocrebanine has a higher affinity for toll-like receptor 4/myeloid differentiation primary response 88 signalling targets and the COX-2 protein than native ligands. Thus, our findings highlight the potential anti-inflammatory effects of oxocrebanine and suggest that certain alkaloids of S. pierrei could be used to treat inflammatory diseases.
Asunto(s)
Aporfinas , Stephania , Antiinflamatorios/metabolismo , Antiinflamatorios/farmacología , Aporfinas/metabolismo , Aporfinas/farmacología , Ciclooxigenasa 2/metabolismo , Lipopolisacáridos/farmacología , Macrófagos , Simulación del Acoplamiento Molecular , FN-kappa B/metabolismo , Óxido Nítrico/metabolismo , Óxido Nítrico Sintasa de Tipo II/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Stephania/metabolismoRESUMEN
Five new alkaloids (1-5), including three new aporphine alkaloids and two new phenanthrene alkaloids, together with 10 known compounds (6-15) were obtained from the roots of Stephania tetrandra. Their structures were elucidated by spectroscopic methods, single-crystal X-ray diffraction, and electronic circular dichroism analyses. Compounds 7-10, and 13 showed antioxidant activities with malondialdehyde (MDA) inhibitory rates of 62.50 ± 1.91 to 98.44 ± 0.34% at the concentration of 10 µM.
Asunto(s)
Alcaloides/farmacología , Antioxidantes/farmacología , Aporfinas/farmacología , Fenantrenos/farmacología , Stephania tetrandra/química , Alcaloides/aislamiento & purificación , Animales , Antioxidantes/aislamiento & purificación , Aporfinas/aislamiento & purificación , China , Dicroismo Circular , Peroxidación de Lípido , Malondialdehído/antagonistas & inhibidores , Microsomas Hepáticos/efectos de los fármacos , Estructura Molecular , Fenantrenos/aislamiento & purificación , Fitoquímicos/aislamiento & purificación , Fitoquímicos/farmacología , Raíces de Plantas/química , RatasRESUMEN
One new aporphine named tavoyanine A (1), along with four known aporphines laetanine (2), roemerine (3), laurolitsine (4), and boldine (5), and one morphinandienone type sebiferine (6) were isolated from the leaves of Phoebe tavoyana (Meissn.) Hook f. (Lauraceae). The isolation was achieved by chromatographic techniques, and the structural elucidation was performed via spectral methods. This paper also reports the antiplasmodial activity of roemerine (3), laurolitsine (4), boldine (5), and sebiferine (6). The results showed that 3-6 have a potent inhibitory activity against the growth of Plasmodium falciparum 3D7 clone, with IC50 values of 0.89, 1.49, 1.65, and 2.76 µg/ml, respectively.
Asunto(s)
Alcaloides , Antimaláricos , Aporfinas , Lauraceae , Estructura Molecular , Extractos Vegetales , Hojas de la Planta , Plasmodium falciparumRESUMEN
Three undescribed aporphine alkaloids dasymaroine A (1), 3-methoxyoxoputerine N-oxide (2), and dasymaroine B (3), along with nine known analogues (4-12) were isolated from the stems of Dasymaschalon rostratum Merr. The structures were elucidated using spectroscopic methods and by comparison with published NMR spectroscopic data. Compound 1 is a rarely reported nitro aporphine alkaloid and its absolute configuration was defined based on negative specific rotation and single-crystal X-ray diffraction. Compound 2 represents the first example of oxoaporphine alkaloid N-oxide. All compounds were evaluated for their activities of six pathogenic bacteria, 1 exhibited significant inhibition against Escherichia coli and Saphylococcus aureus with MIC values of 1.2 and 2.5⯵M, respectively. As well as compounds 1-5, 7, 10, 12 were evaluated for their anti-HIV activities with EC50 ranged from 1.93 to 9.70⯵M.
Asunto(s)
Alcaloides/farmacología , Annonaceae/química , Antibacterianos/farmacología , Fármacos Anti-VIH/farmacología , Aporfinas/química , Extractos Vegetales/farmacología , Tallos de la Planta/química , Bacterias/efectos de los fármacos , VIH/efectos de los fármacos , Estructura MolecularRESUMEN
Nine compounds were isolated from chloroform fraction of Houttuynia cordata,and the isolates were identified as follows:( S)-5,6,6 a,7-tetrahydro-2,10-dimethoxy-4 H-dibenzo [DE,G] quinoline-1,9-diol( 1),( +)-isoboldine ß-N-oxide( 2),liriotulipiferine( 3),telitoxinone( 4),isoboldine( 5),(-)-clovane-2ß,9α-diol( 6),benzoic acid( 7),acantrifoside E( 8),and dibutyl phthalate( 9). Among them,compound 1 was new,and compounds 2-9 were reported from this species for the first time.
Asunto(s)
Medicamentos Herbarios Chinos/química , Houttuynia/química , Fitoquímicos/análisis , Extractos Vegetales/química , CloroformoRESUMEN
Nine compounds were isolated from chloroform fraction of Houttuynia cordata,and the isolates were identified as follows:( S)-5,6,6 a,7-tetrahydro-2,10-dimethoxy-4 H-dibenzo [DE,G] quinoline-1,9-diol( 1),( +)-isoboldine β-N-oxide( 2),liriotulipiferine( 3),telitoxinone( 4),isoboldine( 5),(-)-clovane-2β,9α-diol( 6),benzoic acid( 7),acantrifoside E( 8),and dibutyl phthalate( 9). Among them,compound 1 was new,and compounds 2-9 were reported from this species for the first time.
Asunto(s)
Cloroformo , Medicamentos Herbarios Chinos , Química , Houttuynia , Química , Fitoquímicos , Extractos Vegetales , QuímicaRESUMEN
Three undescribed aporphine alkaloids laurodionine B (1), illigerine A (2), and N-formyl-laurolitsine (3) were isolated from the methanolic extracts of the Chinese medicinal plant, Illigera aromatica, together with three known analogues (4-6). The chemical structures of 1-6 were identified by spectroscopic methods including 1D and 2D NMR (1H, 13C, COSY, HSQC, and HMBC) and high resolution mass spectrometry (HRESIMS). Compounds 1-3 showed moderate inhibitory activities in vitro against two cultured tumor cell lines, Hela and SMMC7721, with IC50 values of 32.42-62.90⯵M. Only compound 1 had in vitro cytotoxic activity against Bcap37â¯cells, with the IC50 value of 90.61⯵M.
Asunto(s)
Antineoplásicos Fitogénicos/farmacología , Aporfinas/farmacología , Medicamentos Herbarios Chinos/farmacología , Hernandiaceae/química , Antineoplásicos Fitogénicos/química , Antineoplásicos Fitogénicos/aislamiento & purificación , Aporfinas/química , Aporfinas/aislamiento & purificación , Proliferación Celular/efectos de los fármacos , China , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales , Medicamentos Herbarios Chinos/química , Medicamentos Herbarios Chinos/aislamiento & purificación , Humanos , Medicina Tradicional China , Estructura Molecular , Relación Estructura-Actividad , Células Tumorales CultivadasRESUMEN
Three new monoterpene phenylpropionic acid esters, illigerates A-C (1-3), and one new aporphine alkaloid, illigeranine (4), as well as four known ones, actinodaphnine (5), nordicentrine (6), 8-hydroxy carvacrol (7), and 3-hydroxy-α,4-dimethyl styrene (8), were isolated from the tubers of Illigera aromatica. The structures of 1-4 were identified by HRESIMS, 1D and 2D NMR, and electronic circular dichroism spectra. Compound 1 potently inhibited NO production in LPS-stimulated RAW264.7 cells with an IC50 value of 18.71 ± 0.85 µM; compound 1, 3, and 4 showed moderate butyrylcholinesterase inhibitory activities with the IC50 values of 46.86 ± 0.65, 53.51 ± 0.71, and 31.62 ± 1.15 µM, respectively. Compound 4 showed weak AChE inhibitory activity with an IC50 value of 81.69 ± 2.07 µM, and compounds 5 and 6 possessed moderate AChE inhibitory activities with the IC50 values of 47.74 ± 1.66 and 40.28 ± 2.73 µM, respectively. This paper provides a chemical structure and bioactive foundation for using I. aromatica as an herbal medicine.
Asunto(s)
Aporfinas/farmacología , Inhibidores de la Colinesterasa/farmacología , Ésteres/farmacología , Hernandiaceae/química , Monoterpenos/farmacología , Óxido Nítrico/metabolismo , Acetilcolinesterasa/metabolismo , Animales , Aporfinas/química , Aporfinas/aislamiento & purificación , Butirilcolinesterasa/metabolismo , Inhibidores de la Colinesterasa/química , Inhibidores de la Colinesterasa/aislamiento & purificación , Relación Dosis-Respuesta a Droga , Ésteres/química , Ésteres/aislamiento & purificación , Lipopolisacáridos/antagonistas & inhibidores , Lipopolisacáridos/farmacología , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Ratones , Estructura Molecular , Monoterpenos/química , Monoterpenos/aislamiento & purificación , Óxido Nítrico/biosíntesis , Teoría Cuántica , Células RAW 264.7 , Relación Estructura-ActividadRESUMEN
An unusual proaporphine alkaloid bearing an isopropanenitrile group at isoquinoline nitrogen, named epiganine A (1) and a new aporphine alkaloid, epiganine B (2), together with eight known alkaloids, pronuciferine (3), dehydrodicentrine (4), romerine (5), romeline (6), N-methylcalycinine (7), phanostenine (8), dicentrine (9), and N-methyllaurotetanine (10), were isolated from the roots of Stephania epigaea. The absolute configuration of 1 was determined by calculating electronic circular dichroism (ECD) and comparing with experimental data. Compounds 2 and 4 showed strong acetylcholinesterase (AChE) inhibitory effects with the IC50 values of 4.36 and 2.98µM, respectively. Compounds 5-9 also exhibited potent AChE inhibitory activities.