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1.
Front Pharmacol ; 13: 993498, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36506533

RESUMO

Osteoarthritis (OA) is a multifactorial and chronic degenerative joint disease. Due to the adverse effects of currently used drugs, a safer and more effective therapy for treating OA is needed. Peroxisome proliferator-activated receptor-γ (PPARγ) is a key protein protecting cartilage. DNMT1-mediated hypermethylation of PPARγ promoter leads to its suppression. Therefore, DNMT1 might be an effective target for exerting cartilage protective effects by regulating the epigenetic expression of PPARγ. Dabushen decoction (DD) is a representative prescription of Dunhuang ancient medical prescription, which has a potential therapeutic effect on OA. So far, the research of the efficacy and material basis of DD in the treatment of OA remains unclear. In this study, Micro-CT, HE staining, S-O staining, and immunohistochemistry analysis were used to demonstrate that DD increased the expression of PPARγ and collagen synthesis in an OA rat model. Next, the structure of DNMT1 was used to screen the active constituents of DD by molecular docking method for treatment OA. Seven potential active constituents, including isoliquiritigenin, emodin, taxifolin, catalpol, alisol A, zingerone, and schisandrin C were hited. The protective effect of the potential active constituents to chondrocytes were evaluated by protein capillary electrophoresis, immunofluorescence assays, and ex vivo culture of rat knee cartilage. The five constituents, such as alisol A, emodin, taxifolin, isoliquiritigenin, and schisandrin C could promote the expression of PPARγ and ameliorate IL-1ß-induced downregulation of collagen II and the production of MMP-13. Alisol A and Emodin could effectively mitigate cartilage damage. At last, molecular dynamics simulations with MM-GBSA method was applied to investigate the interaction pattern of the active constituents and DNMT1 complexes. The five constituents, such as alisol A, emodin, taxifolin, isoliquiritigenin, and schisandrin C achieved a stable binding pattern with DNMT1, in which alisol A has a relatively high binding free energy. In conclusion, this study elucidates that the active constituents of DD (alisol A, emodin, taxifolin, isoliquiritigenin, and schisandrin C) could ameliorate osteoarthritis via PPARγ preservation by targeting DNMT1.These findings facilitated clinical use of DD and provided a valuable strategy for developing natural epigenetic modulators from Chinese herbal formula.

2.
Chem Biodivers ; 19(4): e202100946, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35253972

RESUMO

We identified two new diterpenoidal acrocalyenes A (1) and B (2) through chemical investigation on Acrocalymma sp., a plant-associated fungus from the tender stem isolates of Sinomenium acutum collected from the Qinling Mountains, along with seven already-recognized compounds (3-9). The HR-ESI-TOF-MS and 1D/2D NMR data were utilized for structural elucidation of these compounds, and the single-crystal X-ray diffraction was employed for absolute configuration clarification of the novel acrocalyenes 1 and 2. Bioassays revealed that the cytotoxicities of compounds 2, 4, 6, 7, and 8 against three human carcinoma cells (RKO, HeLa and HCC-1806) were moderate to strong, with IC50 between 6.70-38.82 µM. These isolates were also evaluated for their fungal resistant potentials against Botrytis cinerea, Fusarium culmorum and Fusarium solani, in which 3 displayed significant inhibitory effects on all three phytopathogenic fungi, showing respective MIC of 50, 25 and 25 µM.


Assuntos
Ascomicetos , Carcinoma Hepatocelular , Diterpenos , Neoplasias Hepáticas , Antifúngicos/química , Antifúngicos/farmacologia , Ascomicetos/química , Diterpenos/química , Diterpenos/farmacologia , Humanos , Sinomenium
3.
Nat Prod Res ; 34(20): 2945-2951, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31081703

RESUMO

A pair of new neo-clerodane diterpenoid epimers, 3S-methoxyl-teucvin (1) and 3R-methoxyl-teucvin (2), were isolated from the Roots of Croton crassifolius. Their structures were completely established on the basis of spectroscopic methods, and the absolute configurations were determined by analysis of electronic circular dichroism (ECD) spectroscopy and X-ray diffraction analysis. Compounds 1 and 2 exhibited anti-inflammatory activities with IC50 values of 0.82 and 0.54 µM, respectively, while the IC50 value of dexamethasone as a positive control was found to be 0.14 µM.


Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Croton/química , Diterpenos Clerodânicos/química , Diterpenos Clerodânicos/farmacologia , Animais , Anti-Inflamatórios/análise , Anti-Inflamatórios não Esteroides/química , Dicroísmo Circular , Cristalografia por Raios X , Diterpenos , Avaliação Pré-Clínica de Medicamentos , Furanos , Espectroscopia de Ressonância Magnética , Camundongos , Raízes de Plantas/química , Células RAW 264.7
4.
Bioorg Med Chem Lett ; 28(3): 515-518, 2018 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-29295796

RESUMO

Four new diphenyl ether derivatives, sinopestalotiollides A-D (1-4), one new natural α-pyrone product (11), as well as twelve known compounds (5-1 7), were obtained from the ethyl acetate extract of the endophytic fungus Pestalotiopsis palmarum isolated from the leaves of medicinal plant Sinomenium acutum (Thunb.) Rehd et Wils. The structures were elucidated by HR-ESI-MS and NMR spectrometry data. Bioassay experiments revealed that compounds 1-4 and 11 exhibited strong to weak cytotoxicities against three human tumor cell lines Hela, HCT116 and A549.


Assuntos
Antineoplásicos/farmacologia , Éteres Fenílicos/farmacologia , Xylariales/química , Células A549 , Antineoplásicos/química , Antineoplásicos/isolamento & purificação , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Células HCT116 , Células HeLa , Humanos , Estrutura Molecular , Éteres Fenílicos/química , Éteres Fenílicos/isolamento & purificação , Sinomenium/microbiologia , Relação Estrutura-Atividade
5.
RSC Adv ; 8(57): 32597-32600, 2018 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-35547701

RESUMO

A one-pot approach to substituted 1,2,4-triazolo[4,3-a]pyridines has been developed that is based on a KI-catalyzed oxidative cyclization of α-keto acids and 2-hydrazinopyridines. This transition-metal-free procedure was highly efficient and shows good economical and environmental advantages.

6.
Bioorg Med Chem Lett ; 27(9): 1993-1998, 2017 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-28343876

RESUMO

One new flavone hydrate named lobatflavate (1), one new chromone named lobatchrosin (2), and one new isoflavone named 3S,4R-tuberosin (3), along with four known isoflavone analogues (4-7), were isolated from the traditional Chinese medicinal plant of Pueraria lobata (Willd.) ohwi. Their structures were elucidated by extensive spectroscopic methods of IR, UV, HR-ESI-MS, 1D and 2D NMR. The absolute configuration of 3 was determined by CD spectrum associated with TD-DFT calculation analysis. All compounds except for 2 were assayed the inhibitory activity against α-glucosidase. Every tested compound was proved to be more active than positive control of acarbose. Of which 1 and 4 showed significant activity with IC50 value of 1.79µM and 23.01µM (IC50 of acarbose was 1998.79µM). Enzyme kinetic experiments revealed that 1 was irreversible whereas 4 was reversible and non-competitive α-glucosidase inhibitors. Moreover, structure-activity relationship was discussed and the docking studies of 1, 3 and 4 were also carried out.


Assuntos
Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/farmacologia , Inibidores de Glicosídeo Hidrolases/química , Inibidores de Glicosídeo Hidrolases/farmacologia , Pueraria/química , Cromonas/química , Cromonas/farmacologia , Flavonas/química , Flavonas/farmacologia , Humanos , Hipoglicemiantes/química , Hipoglicemiantes/farmacologia , Isoflavonas/química , Isoflavonas/farmacologia , Simulação de Acoplamento Molecular , Relação Estrutura-Atividade , alfa-Glucosidases/metabolismo
7.
Org Biomol Chem ; 11(40): 6960-6, 2013 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-24056968

RESUMO

New Tb(iii) and Eu(iii) complexes have been synthesized as potential pH probes using a tripodal substituted-salicylic ligand (H3). Among them, this carboxylate ligand is found to be a good sensitizer for Tb(iii) emission owing to the superior match of the triplet energy level of the ligand with the (5)D4 emitting level of Tb(iii). The resulting · complex exhibited high sensitivity in the physiological pH range with significant "off-on-off" fluorescence changes in aqueous solution. Furthermore, this unique rare-earth complex has been successfully used to monitor pH variations within HeLa cells and with filter papers.


Assuntos
Corantes Fluorescentes/química , Compostos Organometálicos/química , Ácido Salicílico/química , Térbio/química , Células HeLa , Humanos , Concentração de Íons de Hidrogênio , Modelos Moleculares , Estrutura Molecular , Espectrometria de Fluorescência
8.
Life Sci ; 90(23-24): 929-33, 2012 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-22569298

RESUMO

AIMS: Inhibition of acetylcholinesterase (AChE) is still considered as a strategy for the treatment of neurological disorders such as Alzheimer's disease (AD). Many plant derived alkaloids (such as huperzine A, galanthamine and rivastigmine) are known for their AChE inhibitory activity. The aim of the present work was to isolate and identify new AChE inhibitors from Holarrhen antidysenterica. MAIN METHODS: These compounds were tested for AChE inhibiting activity by the Ellman's method in 96-well microplates. In addition, molecular modeling was performed to explore the binding mode of inhibitors 1-5 at the active site of AChE, and the preliminary structure-activity relationships (SARs) were discussed. KEY FINDINGS: In the course of searching for AChE inhibitors from herb medicines, the total alkaloidal extract from the seeds of H. antidysenterica was found having potent AChE inhibitory activity with an IC(50) value of 6.1 µg/mL. Further bioactivity-guided chromatographic fractionation afforded five steroidal alkaloids, conessine 1, isoconessimine 2, conessimin 3, conarrhimin 4 and conimin 5. All the isolated compounds, except for 2, showed strong AChE inhibiting activity with IC(50) values ranging from 4 to 28 µM. The most active inhibitor is compound 3 with an IC(50) value of 4 µM. The mode of AChE inhibition by 3 was reversible and non-competitive. SIGNIFICANCE: The results suggest that these alkaloids could be potential candidates for further development of new drugs against AD.


Assuntos
Alcaloides/farmacologia , Inibidores da Colinesterase/farmacologia , Holarrhena/química , Extratos Vegetais/farmacologia , Esteroides/farmacologia , Alcaloides/química , Alcaloides/isolamento & purificação , Inibidores da Colinesterase/química , Inibidores da Colinesterase/isolamento & purificação , Concentração Inibidora 50 , Modelos Moleculares , Extratos Vegetais/química , Sementes , Esteroides/química , Esteroides/isolamento & purificação , Relação Estrutura-Atividade
9.
Nat Prod Res ; 26(1): 22-8, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-21714741

RESUMO

Geissoschizine methyl ether (1), a newly discovered strong acetylcholinesterase (AChE) inhibitor, along with six weakly active alkaloids, vallesiachotamine (2), hisuteine (3), hirsutine (4), isorhynchophylline (5), cisocorynoxeine (6) and corynoxeine (7) have been isolated from Uncaria rhynchophylla. Geissoschizine methyl ether (1) inhibited 50% of AChE activity at concentrations of 3.7 ± 0.3 µg mL(-1) while the IC(50) value of physostigmine as a standard was 0.013 ± 0.002 µg mL(-1). The mode of AChE inhibition by 1 was reversible and non-competitive. In addition, molecular modelling was performed to explore the binding mode of inhibitor 1 at the active site of AChE.


Assuntos
Inibidores da Colinesterase/análise , Medicamentos de Ervas Chinesas/química , Indóis/análise , Modelos Moleculares , Uncaria/química , Alcaloides/análise , Sítios de Ligação/genética , Bioensaio , Inibidores da Colinesterase/química , Inibidores da Colinesterase/farmacologia , Alcaloides Indólicos , Indóis/química , Indóis/farmacologia , Concentração Inibidora 50 , Estrutura Molecular , Ligação Proteica
10.
Fitoterapia ; 83(1): 137-41, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22037568

RESUMO

Pingbeimunone A (1), a new compound, together with the known ussuriedine (2), benzo[7,8]fluoreno[2,1-b]quinolizine cevane-3,6,16,20-tetrol (3), ebeiedinone (4), pingbeimine C (5) and verticine (6) were isolated from Fritillaria ussuriensis. The structure was elucidated on the basis of spectral analysis (IR, NMR and MS spectroscopy). In addition, their AChE inhibitory activities were also tested.


Assuntos
Alcaloides/química , Fritillaria/química , Estrutura Molecular
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