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1.
Arch Pharm Res ; 47(5): 410-441, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38750332

RESUMO

The genus Tamarix in the Tamaricaceae family consists of more than 100 species of halophyte plants worldwide that are mainly used to improve saline-alkali land and for coastal windbreaks, sand fixation, and afforestation in arid areas. A considerable number of species in this genus are also used as traditional medicines to treat various human diseases, especially in Asian and African countries. This review presents a comprehensive summary of 655 naturally occurring compounds derived from the genus Tamarix, categorized into flavonoids (18.0%), phenols (13.9%), tannins (9.3%), terpenoids (10.5%), essential oils (31.0%), and others (17.3%). The investigation revealed that the crude extracts and phytochemicals of this genus exhibited significant therapeutic potential, including anti-inflammatory, anti-Alzheimer, anticancer, antidiabetic, antibacterial, and antifungal activities. Six species of Tamarix have anticancer effects by causing cancer cell death, inducing autophagy, and stopping cell division. Seven species from the same genus have the potential for treating diabetes by inhibiting α-glycosidase activity, suppressing human islet amyloid polypeptide, regulating blood glucose levels, and modulating autophagy or inflammation. The focus on antibacterial and antidiabetic effects is due to the presence of volatile oil and flavonoid components. Extensive research has been conducted on the biological activity of 30 constituents, including 15 flavonoids, 5 phenols, 3 terpenoids, 1 tannin, and 6 others. Therefore, future research should thoroughly study the mechanisms of action of these and similar compounds. This is the most comprehensive review of the phytochemistry and pharmacological properties of Tamarix species, with a critical assessment of the current state of knowledge.


Assuntos
Compostos Fitoquímicos , Tamaricaceae , Humanos , Tamaricaceae/química , Compostos Fitoquímicos/farmacologia , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/química , Animais , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Hipoglicemiantes/farmacologia , Hipoglicemiantes/química , Hipoglicemiantes/isolamento & purificação , Antineoplásicos Fitogênicos/farmacologia , Antineoplásicos Fitogênicos/isolamento & purificação , Antineoplásicos Fitogênicos/química
2.
J Appl Toxicol ; 44(3): 344-354, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37718569

RESUMO

Narcissin is a natural flavonoid from some edible and traditional medicinal plants. It has been proven to have multiple biological functions and exhibits potential therapeutic effects on hypertension, cancer, and Alzheimer's disease. However, the toxicity of narcissin is largely unknown. Here, we revealed that narcissin treatment led to reduced hatchability, increased malformation rate, shorter body length, and slowed blood flow in zebrafish. Furthermore, bradycardia, pericardial edema, increased SV-BA distance, diminished stroke volume, ejection fraction, and ventricular short-axis shortening rate were also found. A large accumulation of ROS, increased apoptotic cells, and histopathological changes were detected in the heart region. Moreover, the gene expression profiles and molecular docking analysis indicated that Nrf2/HO-1 and calcium signaling pathways were involved in narcissin-induced toxicity. In conclusion, here we provide the first evidence that demonstrates narcissin-induced developmental toxicity and cardiotoxicity in zebrafish via Nrf2/HO-1 and calcium signaling pathways for the first time.


Assuntos
Flavonóis , Fator 2 Relacionado a NF-E2 , Peixe-Zebra , Animais , Peixe-Zebra/metabolismo , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , Cardiotoxicidade , Sinalização do Cálcio , Simulação de Acoplamento Molecular , Embrião não Mamífero , Estresse Oxidativo
3.
Artigo em Inglês | MEDLINE | ID: mdl-37915543

RESUMO

A total of 18% of global breast cancer (BC) deaths are attributed to BC in China, making it one of the five most common cancers there. There has been a steady rise in BC morbidity and mortality in women in the last few years and it is now a leading cancer among Chinese women. Conventional treatments for BC are currently effective but have several limitations and disadvantages, and Traditional Chinese medicine (TCM) plays a vital role in the overall process of cancer prevention and therapy. It is known that TCM can treat a variety of conditions at a variety of sites and targets. In recent years, increasingly, research has been conducted on TCM's ability to treat BC. TCM has shown positive results in the treatment of breast cancer and the adverse effects of radiotherapy and chemotherapy. This review describes the progress of clinical observation and mechanism research of TCM in the treatment of breast cancer in recent years. It provides some ideas and theoretical basis for the treatment of BC with TCM.

4.
J Adv Res ; 2023 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-37949300

RESUMO

BACKGROUND: Flavonoids are one of the most important metabolites with vast structural diversity and a plethora of potential pharmacological applications, which have drawn considerable attention in the laboratory. Nevertheless, it remains uncertain how many candidates were progressed to clinical application. AIM OF REVIEW: We carried out a critical review of natural and semi-synthetic flavonoid drugs and candidates undergoing different clinical phases worldwide by applying an adequate search method and conducted a brief cheminformatic and bioinformatic analysis. It was expected that the obtained results might narrow the screening scope and reduce the cost of drug research and development. KEY SCIENTIFIC CONCEPTS OF REVIEW: To our knowledge, this is the most systematic summarization of flavonoid-based drugs and clinical candidates to date. It was found that a total of 19 flavonoid-based drugs have been approved for the market, and of these, natural flavonoids accounted for 52.6%. Besides, a total of 36 flavonoid-based clinical candidates are undergoing or suspended in different phases, and of these, natural flavonoids account for 44.4%. Thus, natural flavonoids remain the best option for finding novel agents/active templates, and when investigated in conjunction with synthetic chemicals and biologicals, they offer the potential to discover novel structures that can lead to effective agents against a variety of human diseases. Additionally, flavonoid-based marketed drugs have been successful in cardiovascular treatment, and the related drugs account for more than 30% of marketed drugs. However, the use of flavonoids as antineoplastic and immunomodulating agents is not likely for approximately 50% of the candidates suspended in the clinical stage. Interestingly, the marketed drugs covered a broader range of chemical spaces based on size, polarity, and three-dimensional structure compared to the clinical candidates. In addition, flavonoid glycosides with poor oral bioavailability account for 36.8% of the marketed drugs, and thus, they could be thoroughly investigated.

5.
PPAR Res ; 2023: 4481354, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37334066

RESUMO

Breast cancer (BC) is the most common type of cancer among females. Peroxisome proliferator-activated receptor gamma (PPARG) can regulate the production of adipocyte-related genes and has anti-inflammatory and anti-tumor effects. Our aim was to investigate PPARG expression, its possible prognostic value, and its effect on immune cell infiltration in BC, and explore the regulatory effects of natural drugs on PPARG to find new ways to treat BC. Using different bioinformatics tools, we extracted and comprehensively analyzed the data from the Cancer Genome Atlas, Genotype-Tissue Expression, and BenCaoZuJian databases to study the potential anti-BC mechanism of PPARG and potential natural drugs targeting it. First, we found that PPARG was downregulated in BC and its expression level correlates with pathological tumor stage (pT-stage) and pathological tumor-node-metastasis stage (pTNM-stage) in BC. PPARG expression was higher in estrogen receptor-positive (ER+) BC than in estrogen receptor-negative (ER-) BC, which tends to indicate a better prognosis. Meanwhile, PPARG exhibited a significant positive correlation with the infiltration of immune cells and correlated with better cumulative survival in BC patients. In addition, PPARG levels were shown to be positively associated with the expression of immune-related genes and immune checkpoints, and ER+ patients had better responses to immune checkpoint blocking. Correlation pathway research revealed that PPARG is strongly associated with pathways, such as angiogenesis, apoptosis, fatty acid biosynthesis, and degradation in ER+ BC. We also found that quercetin is the most promising natural anti-BC drug among natural medicines that upregulate PPARG. Our research showed that PPARG may reduce BC development by regulating the immune microenvironment. Quercetin as PPARG ligands/agonists is a potential natural drug for BC treatment.

6.
J Ethnopharmacol ; 308: 116273, 2023 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-36822343

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Vitex rotundifolia L. f. and Vitex trifolia L. belong to the genus Vitex, and Vitex rotundifolia L. f. evolved from Vitex trifolia L. Both are essential ethnic medicinal plants with a long history, commonly used to treat headaches, fever, diarrhea, hair loss, wound recovery, and other diseases. AIM OF THE REVIEW: The research status of Vitex trifolia L. and its relative species Vitex rotundifolia L. f. were reviewed from the aspects of traditional medicinal use, phytochemistry, and pharmacological activities, to provide a reference for the further development and utilization of Vitex rotundifolia L. f. and Vitex trifolia L. MATERIALS AND METHODS: In this paper, a comprehensive search of published literature was conducted through various books and online databases to obtain relevant information on Vitex rotundifolia L. f. and Vitex trifolia L. The search terms "(Vitex rotundifolia) OR (Vitex trifolia) OR (Fructus viticis)" were entered in PubMed, Web of Science, China national knowledge infrastructure (CNKI), Wanfang Data, Baidu Scholar, respectively. In addition to setting the year threshold of "2018-2022" on Baidu Scholar, other databases searched all fields and found 889, 283, 1263, 1023, and 147 articles, respectively. Among them, review, repetition, overlapping data, and other reasons were excluded, and finally, a total of 164 articles were included in the review study. RESULTS: A total of 369 compounds have been identified, including 159 terpenoids, 51 flavonoids, 83 phenylpropanoids, and 76 other compounds. Pharmacological studies have shown that Vitex rotundifolia L. f. and Vitex trifolia L. have a variety of pharmacological activities, such as anti-tumor, analgesic, antipyretic, anti-inflammatory, antioxidant, antibacterial, and estrogen-like activity. Modern clinical use for treating cold headaches, diarrhea dysentery, irregular menstruation, and other diseases. CONCLUSIONS: As traditional medicinal plants, Vitex rotundifolia L. f. and Vitex trifolia L. have wealthy chemical constituents and extensive pharmacological activities and are widely used in clinical practice from traditional to modern times. However, the research on the pharmacological activities of Vitex rotundifolia L. f. and Vitex trifolia L. is not in-depth, and the potential active components still need to be explored.


Assuntos
Plantas Medicinais , Vitex , Vitex/química , Medicina Tradicional , Anti-Inflamatórios/farmacologia , China , Compostos Fitoquímicos , Etnofarmacologia , Extratos Vegetais/farmacologia
7.
Food Chem ; 405(Pt B): 134968, 2023 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-36442239

RESUMO

Suaeda salsa L. (Chenopodiaceae) is a wild vegetable distributed along the northern coast of China. Searching for potential agents with health benefits from S. salsa L. led to the identification of 14 flavonoids (1-14), eight phenolic acids (15-22), one coumarin (23), one benzoquinone (24), two sesquiterpenes (25, 26), and three lignins (27-29) from an aqueous ethanol (EtOH) extract of the above-ground whole plant using various column chromatographic methods. High-resolution electrospray ionization mass spectrometry (HRESIMS) analyses and nuclear magnetic resonance (1H and 13C NMR) spectroscopy were adopted to examine the structural properties of the compounds. To date, our study is the first to identify 20 compounds from this genus. Some compounds exhibited significant health benefits in zebrafish models. Compounds 2, 4, 23, and 28 significantly improved oxidative damage, while compounds 1-5, 7, 11, 13, 18, 19, and 23 significantly improved zebrafish lateral line neuromast inflammation. Additionally, compounds 1, 4, 8, 13, and 16 significantly promoted zebrafish angiogenesis, while compounds 3-5 and 18 significantly improved zebrafish arrhythmia. Furthermore, a flavonoid-targeted metabolomics study revealed that flavanone was the precursor of all of the flavonoids and had its highest accumulation in August, while the others showed their highest accumulation in September. Thus, the best time to harvest most of the bioactive polyphenols is during September. The present study revealed that the wild vegetable S. salsa L. might be developed as a potential cardioprotective functional food.


Assuntos
Chenopodiaceae , Polifenóis , Animais , Polifenóis/farmacologia , Verduras , Peixe-Zebra , Flavonoides/farmacologia
8.
Front Oncol ; 12: 905868, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36457514

RESUMO

The literature related to TMZ research in the Web of Science (WOS) database was analyzed using bibliometrics and visualization by Citespace and VOSviewer.The publication status (number of publications, institutions, and frequency of citations), collaborations, and research focus was analyzed to clarify the current situation of TMZ research. And the recent research on TMZ provides a detailed summary. Based on objective data analysis, this study provides a complete analysis portraying the progression of historical milestones in TMZ development and future research directions from various TMZ research domains.

9.
Medicine (Baltimore) ; 101(44): e31534, 2022 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-36343021

RESUMO

We aimed to compare the effect of minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) and Crenel lateral interbody fusion (CLIF) on single segmental lumbar degenerative disease. Patients with single segmental lumbar degenerative disease undergoing MIS-TLIF (n = 28) and CLIF (n = 28) were enrolled from April to October 2017. Preoperative medical history, anthropometric data, and clinical data were recorded. Visual analogue scores and Oswestry disability index (ODI) were assessed. Radiography was performed before and after surgery. X-ray films were evaluated according to the Bridwell method, visual analogue scores and ODI scores were evaluated. There were no significant differences in the gender, age, clinical diagnosis, involved segment or preoperative ODI score between 2 groups (P > .05). During 12-month follow-up, MIS-TLIF group had less intraoperative blood loss, drainage, postoperative bedridden time, and hospital stay (P < .05), but more operation time and radiation exposure time compared with CLIF group (P < .05). CLIF group reported less pain than MIS-TLIF group (P > .05). Both groups had similar lumbar fusion rate (P > .05). Overall, CLIF has less complications, less trauma and faster recovery for the treatment of single segmental lumbar degenerate disease when compared with MIS-TLIF. Evaluation of more patients and long-term follow-up are still needed to further validate our findings.


Assuntos
Degeneração do Disco Intervertebral , Fusão Vertebral , Humanos , Fusão Vertebral/métodos , Vértebras Lombares/diagnóstico por imagem , Vértebras Lombares/cirurgia , Degeneração do Disco Intervertebral/diagnóstico por imagem , Degeneração do Disco Intervertebral/cirurgia , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Resultado do Tratamento , Estudos Retrospectivos
10.
Pharmaceuticals (Basel) ; 15(5)2022 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-35631427

RESUMO

As one of the most characteristic ingredients of glandular trichome secretions from Nicotiana tabacum L. (tobacco), natural cembrenediols, namely, (1S,2E,4S,6R,7E,11E)-2,7,11-cembratriene-4,6-diol (α-cembrenediol/α-CBD) and its C-4 epimer (ß-cembrenediol/ß-CBD), have attracted considerable attention for their potent antitumor, neuroprotective, antimicrobial, and other activities. Many researchers are committed to exploring the possibility of utilizing these two cembrenediols and their derivatives both in human medicine and in agricultural fungicides. To the best of our knowledge, this review is the first to provide a comprehensive summary of the chemical modifications and bioactivities of α- and ß-CBD from their discovery to the present day; the review highlights their potential medicinal value for humans. The extensive references from 1962 to 2022 provided herein were systematically gathered from the SciFinder, Web of Science, and Google Scholar databases. We expect this review to assist in providing practical ideas for future drug development based on α- and ß-CBD and in further facilitating the utilization of the tobacco cembrenediols.

11.
Nat Prod Res ; 35(24): 6134-6140, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33016130

RESUMO

One new xanthone, chryxanthone C (1), together with four known analogues (2-5), were isolated from the cultures of Paecilamyces sp. TE-540, an endophytic fungus obtained from the leaves of Nicotiana tabacum L. The structure of 1 was elucidated by comprehensive spectral analysis including HRESIMS and 1D/2D NMR, which were confirmed by Cu Kα X-ray crystallography. Compound 1 featured an unusual dihydropyran ring fused to an aromatic ring, rather than the commonly occurring prenyl moiety. The cytotoxicity of compounds 1-5 were evaluated against five human tumour cell lines and 4 exhibited moderate to strong cytotoxicities with IC50 values ranging from 5.6 to 14.2 µM.


Assuntos
Antineoplásicos , Xantonas , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Humanos , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Xantonas/farmacologia
12.
Front Pharmacol ; 11: 570450, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33178020

RESUMO

Fungal secondary metabolites serve as a rich resource for exploring lead compounds with medicinal importance. Diorcinol N (DN), a fungal secondary metabolite isolated from an endophytic fungus, Arthrinium arundinis, exhibits robust anticancer activity. However, the anticancer mechanism of DN remains unclear. In this study, we examined the growth-inhibitory effect of DN on different human cancer cell lines. We found that DN decreased the viability of A3 T-cell leukemia cells in a time- and concentration-dependent manner. Transcriptome analysis indicated that DN modulated the transcriptome of A3 cells. In total, 9,340 differentially expressed genes were found, among which 4,378 downregulated genes and 4,962 upregulated genes were mainly involved in autophagy, cell cycle, and DNA replication. Furthermore, we demonstrated that DN induced autophagy, cell cycle arrest in the G1/S phase, and downregulated the expression of autophagy- and cell cycle-related genes in A3 cells. By labeling A3 cells with acridine orange/ethidium bromide, Hoechst 33,258, and monodansylcadaverine and via transmission electron microscopy, we found that DN increased plasma membrane permeability, structural disorganization, vacuolation, and autophagosome formation. Our study provides evidence for the mechanism of anticancer activity of DN in T-cell leukemia (A3) cells and demonstrates the promise of DN as a lead or even candidate molecule for the treatment of acute lymphoblastic leukemia.

13.
Bioorg Chem ; 104: 104252, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32911187

RESUMO

Sesquiterpenoids with diverse skeleton types are regarded as potential lead compounds in pharmacological and other applications. Herein, we report the discovery of two new cadinane-type sesquiterpenoids, paecilacadinol A (1) and B (2); two new drimane-type sesquiterpenoids, ustusol D (3) and ustusol E (4); and six known analogs (5-10) from the endophytic fungus Paecilomyces sp. TE-540, enriching the structural diversity of naturally occurring sesquiterpenoids. Their planar structures were determined on the basis of detailed interpretation of 1D and 2D NMR spectroscopy and HRESIMS data, while their stereochemical structures were established by X-ray crystallographic analyses for 1 and 3-8 and theoretical calculations for 2. Notably, compounds 1 and 2 represent novel examples of cadinane-type sesquiterpenoids with ether bonds formed by intramolecular dehydration. Compounds 5 and 6 showed moderate activities against acetylcholinesterase (AChE), with IC50 values of 43.02 ± 6.01 and 35.97 ± 2.12 µM, respectively. Docking analysis predicted that 5 bound well in the catalytic pocket of AChE via hydrophobic interactions with Trp84, Gly117, Ser122, and Tyr121 residues, while 6 was located with Asp72 and Ser122 residues.


Assuntos
Inibidores da Colinesterase/farmacologia , Nicotiana/química , Paecilomyces/metabolismo , Sesquiterpenos Policíclicos/farmacologia , Sesquiterpenos/farmacologia , Acetilcolinesterase/metabolismo , Animais , Inibidores da Colinesterase/química , Inibidores da Colinesterase/metabolismo , Relação Dose-Resposta a Droga , Electrophorus , Estrutura Molecular , Paecilomyces/química , Sesquiterpenos Policíclicos/química , Sesquiterpenos Policíclicos/metabolismo , Sesquiterpenos/química , Sesquiterpenos/metabolismo , Relação Estrutura-Atividade
14.
J Agric Food Chem ; 67(43): 11994-12001, 2019 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-31618578

RESUMO

Bioactivity-guided isolation of the endophytic fungus Fusarium sambucinum TE-6L residing in Nicotiana tabacum L. led to the discovery of two new angularly prenylated indole alkaloids (PIAs) with pyrano[2,3-g]indole moieties, amoenamide C (1) and sclerotiamide B (2), and four known biosynthetic congeners (3-6). Their structures were determined by comprehensive spectroscopic techniques, electronic circular dichroism (ECD), and X-ray diffraction. Compound 1 containing the bicyclo[2.2.2]diazaoctane core and indoxyl unit is rarely reported. All the compounds were evaluated for their antimicrobial and insecticidal activities. Notably, compounds 1-3 showed potent inhibitory effects against three human- and one plant-pathogenic bacterium, and seven plant-pathogenic fungi. Compounds 2-4 also exhibited remarkable larvicidal activity against first instar larvae of the cotton bollworm Helicoverpa armigera with mortality rates of 70.2%, 83.2%, and 70.5%, respectively. Further toxicity tests on zebrafish embryos were performed to evaluate the potential toxicity of PIAs. Of significance was that compound 3 in particular exhibited the highest activities but the lowest effects on the hatching of embryos among all the compounds. This study provides a basis for understanding developmental toxicity of PIAs exposure to zebrafish embryos, and also indicates the potential environmental risks of other natural compounds exposure in the aquatic ecosystem.


Assuntos
Anti-Infecciosos/química , Endófitos/química , Fusarium/química , Alcaloides Indólicos/química , Inseticidas/química , Animais , Anti-Infecciosos/metabolismo , Anti-Infecciosos/farmacologia , Bactérias/efeitos dos fármacos , Endófitos/isolamento & purificação , Fungos/efeitos dos fármacos , Fusarium/isolamento & purificação , Alcaloides Indólicos/metabolismo , Alcaloides Indólicos/farmacologia , Inseticidas/metabolismo , Inseticidas/farmacologia , Larva/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Estrutura Molecular , Mariposas/efeitos dos fármacos , Nicotiana/microbiologia , Peixe-Zebra/embriologia
15.
Eur J Med Chem ; 177: 153-170, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31132531

RESUMO

The eukaryotic initiation factor 4E (eIF4E) is an emerging anticancer drug target for specific anticancer therapy as a promising approach to overcome drug resistance and promote chemotherapy antitumor efficacy. A series of bromophenol-thiazolylhydrazone hybrids were designed, synthesized and evaluated for their antitumor activities. Among of them, the most potent compound 3e (EGPI-1) could inhibit the eIF4E/eIF4G interaction. Further mechanism study demonstrated EGPI-1 played an antitumor role in multiple modes of action including regulating the activity of eIF4E by inhibiting the phosphorylation of eIF4E and 4EBP1, disrupting mitochondrial function through the mTOR/4EBP1 signaling pathway, and inducing autophagy, apoptosis and ROS generation. Moreover, EGPI-1 showed good safety and favorable pharmacokinetic properties in vivo. These observations demonstrate that EGPI-1 may serve as an excellent lead compound for the development of new anticancer drugs that target the eIF4E/eIF4G interface and as a chemical genetic probe to investigate the role of the eIF4E in biological processes and human diseases.


Assuntos
Antineoplásicos/farmacologia , Fator de Iniciação 4E em Eucariotos/antagonistas & inibidores , Fator de Iniciação Eucariótico 4G/antagonistas & inibidores , Hidrazonas/farmacologia , Tiazóis/farmacologia , Animais , Antineoplásicos/síntese química , Antineoplásicos/farmacocinética , Antineoplásicos/toxicidade , Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Sítios de Ligação , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Desenho de Fármacos , Fator de Iniciação 4E em Eucariotos/química , Fator de Iniciação 4E em Eucariotos/metabolismo , Fator de Iniciação Eucariótico 4G/metabolismo , Feminino , Células Endoteliais da Veia Umbilical Humana , Humanos , Hidrazonas/síntese química , Hidrazonas/farmacocinética , Hidrazonas/toxicidade , Masculino , Camundongos , Simulação de Acoplamento Molecular , Fosforilação , Ligação Proteica , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/efeitos dos fármacos , Tiazóis/síntese química , Tiazóis/farmacocinética , Tiazóis/toxicidade , Ensaios Antitumorais Modelo de Xenoenxerto
16.
Mar Drugs ; 17(4)2019 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-30987066

RESUMO

A study on the secondary metabolites of Aspergillus sp. XNM-4, which was derived from marine algae Leathesia nana (Chordariaceae), led to the identification of one previously undescribed (1) and seventeen known compounds (2-18). Their planar structures were established by extensive spectroscopic analyses, while the stereochemical assignments were defined by electronic circular dichroism (ECD) calculations. The biological activities of the compounds were assessed on five human cancer cell lines (PANC-1, A549, MDA-MB-231, Caco-2, and SK-OV-3), and one human normal cell line (HL-7702) using an MTT [3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl tetrazolium bromide] assay. Among them, the dimeric naphthopyrones 7, 10 and 12 exhibited potent cytotoxicity. Further mechanism studies showed that 12 induced apoptosis, arrested the cell cycle at the G0/G1 phase in the PANC-1 cells, caused morphological changes and generated ROS; and it induces PANC-1 cells apoptosis via ROS-mediated PI3K/Akt signaling pathway.


Assuntos
Antineoplásicos/farmacologia , Organismos Aquáticos , Aspergillus , Produtos Biológicos/farmacologia , Naftalenos/farmacologia , Pironas/farmacologia , Antineoplásicos/isolamento & purificação , Apoptose/efeitos dos fármacos , Produtos Biológicos/isolamento & purificação , Linhagem Celular Tumoral , Descoberta de Drogas , Ensaios de Seleção de Medicamentos Antitumorais , Pontos de Checagem da Fase G1 do Ciclo Celular/efeitos dos fármacos , Humanos , Naftalenos/isolamento & purificação , Phaeophyceae/microbiologia , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Pironas/isolamento & purificação , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/efeitos dos fármacos
17.
J Med Chem ; 62(6): 3051-3067, 2019 03 28.
Artigo em Inglês | MEDLINE | ID: mdl-30844273

RESUMO

Poly(ADP-ribose) polymerase-1 (PARP-1) is a new potential target for anticancer drug discovery. A series of bromophenol-thiosemicarbazone hybrids as PARP-1 inhibitors were designed, synthesized, and evaluated for their antitumor activities. Among them, the most promising compound, 11, showed excellent selective PARP-1 inhibitory activity (IC50 = 29.5 nM) over PARP-2 (IC50 > 1000 nM) and potent anticancer activities toward the SK-OV-3, Bel-7402 and HepG2 cancer cell lines (IC50 = 2.39, 5.45, and 4.60 µM), along with inhibition of tumor growth in an in vivo SK-OV-3 cell xenograft model. Further study demonstrated that compound 11 played an antitumor role through multiple anticancer mechanisms, including the induction of apoptosis and cell cycle arrest, cellular accumulation of DNA double-strand breaks, DNA repair alterations, inhibition of H2O2-triggered PARylation, antiproliferative effects via the production of cytotoxic reactive oxygen species, and autophagy. In addition, compound 11 displayed good pharmacokinetic characteristics and favorable safety. These observations demonstrate that compound 11 may serve as a lead compound for the discovery of new anticancer drugs.


Assuntos
Antineoplásicos/uso terapêutico , Descoberta de Drogas , Neoplasias/tratamento farmacológico , Fenóis/química , Inibidores de Poli(ADP-Ribose) Polimerases/uso terapêutico , Tiossemicarbazonas/química , Animais , Antineoplásicos/farmacocinética , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Quebras de DNA de Cadeia Dupla/efeitos dos fármacos , Humanos , Peróxido de Hidrogênio/farmacologia , Concentração Inibidora 50 , Camundongos , Neoplasias/patologia , Inibidores de Poli(ADP-Ribose) Polimerases/farmacocinética , Inibidores de Poli(ADP-Ribose) Polimerases/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto
18.
Mar Drugs ; 15(11)2017 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-29104274

RESUMO

A series of bromophenol hybrids with N-containing heterocyclic moieties were designed, and their anticancer activities against a panel of five human cancer cell lines (A549, Bel7402, HepG2, HCT116 and Caco2) using MTT assay in vitro were explored. Among them, thirteen compounds (17a, 17b, 18a, 19a, 19b, 20a, 20b, 21a, 21b, 22a, 22b, 23a, and 23b) exhibited significant inhibitory activity against the tested cancer cell lines. The structure-activity relationships (SARs) of bromophenol derivatives were discussed. The promising candidate compound 17a could induce cell cycle arrest at G0/G1 phase and induce apoptosis in A549 cells, as well as caused DNA fragmentations, morphological changes and ROS generation by the mechanism studies. Furthermore, compound 17a suppression of Bcl-2 levels (decrease in the expression of the anti-apoptotic proteins Bcl-2 and down-regulation in the expression levels of Bcl-2) in A549 cells were observed, along with activation caspase-3 and PARP, which indicated that compound 17a induced A549 cells apoptosis in vitro through the ROS-mediated apoptotic pathway. These results might be useful for bromophenol derivatives to be explored and developed as novel anticancer drugs.


Assuntos
Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Organismos Aquáticos , Fenóis/farmacologia , Animais , Antineoplásicos/química , Linhagem Celular Tumoral/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Fenóis/química , Transdução de Sinais/efeitos dos fármacos , Relação Estrutura-Atividade
19.
Org Biomol Chem ; 15(26): 5480-5483, 2017 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-28654120

RESUMO

Sophopterocarpan A (1), with a novel benzotetrahydrofuran-fused bicyclo [3.3.1] nonane ring, was isolated from the roots of Sophora flavescens Ait. Its unusual structure, including its stereochemistry, was determined on the basis of a comprehensive spectroscopic data analysis. A plausible biogenetic pathway for 1 is presented. Sophopterocarpan A was identified as a potential autophagy activator. Additionally, it was found that 1 exhibited cytotoxic activity in MCF-7 cells with an IC50 of 29.36 µM.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Pterocarpanos/farmacologia , Sophora/química , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Morte Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Modelos Moleculares , Estrutura Molecular , Raízes de Plantas/química , Pterocarpanos/química , Pterocarpanos/isolamento & purificação , Estereoisomerismo , Relação Estrutura-Atividade
20.
J Asian Nat Prod Res ; 19(2): 121-127, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27790920

RESUMO

An ongoing phytochemical investigation of the rhizomes of Atractylodes lancea resulted in the isolation of four new C10-type polyacetylene glycosides (1-4). Their structures were elucidated on the basis of extensive spectroscopic data (UV, IR, 1D and 2D NMR, and HRESIMS). The absolute configurations of compounds 2-4 were determined by comparing the specific rotations of their aglycones. Notably, compounds 2 and 3 exhibited significant hepatoprotective activities against APAP-induced HepG2 cell injury at a concentration of 10 µM. Compounds 2 and 3 showed weak anti-inflammatory effects on LPS-induced NO production in microglia BV2 cells at a concentration of 10 µM.


Assuntos
Atractylodes/química , Glicosídeos/isolamento & purificação , Poli-Inos/isolamento & purificação , Rizoma/química , Animais , Glicosídeos/química , Células Hep G2 , Humanos , Lipopolissacarídeos/farmacologia , Camundongos , Microglia/efeitos dos fármacos , Estrutura Molecular , Óxido Nítrico/biossíntese , Ressonância Magnética Nuclear Biomolecular , Poli-Inos/farmacologia
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