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1.
Biol Res ; 52(1): 55, 2019 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-31601259

RESUMO

BACKGROUND: Epanorin (EP) is a secondary metabolite of the Acarospora lichenic species. EP has been found in lichenic extracts with antimicrobial activity, and UV-absorption properties have been described for closely related molecules; however, its antiproliferative activity in cancer cells has not yet been explored. It has been hypothesized that EP inhibits cancer cell growth. MCF-7 breast cancer cells, normal fibroblasts, and the non-transformed HEK-293 cell line were exposed to increasing concentrations of EP, and proliferation was assessed by the sulforhodamine-B assay. RESULTS: MCF-7 cells exposed to EP were examined for cell cycle progression using flow cytometry, and DNA fragmentation was examined using the TUNEL assay. In addition, EP's mutagenic activity was assessed using the Salmonella typhimurium reverse mutation assay. The data showed that EP inhibits proliferation of MCF-7 cells, and it induces cell cycle arrest in G0/G1 through a DNA fragmentation-independent mechanism. Furthermore, EP's lack of overt cytotoxicity in the normal cell line HEK-293 and human fibroblasts in cell culture is supported by the absence of mutagenic activity of EP. CONCLUSION: EP emerges as a suitable molecule for further studies as a potential antineoplastic agent.


Assuntos
Antineoplásicos/uso terapêutico , Apoptose/efeitos dos fármacos , Neoplasias da Mama/tratamento farmacológico , Proliferação de Células/efeitos dos fármacos , Líquens/química , Antineoplásicos/isolamento & purificação , Fragmentação do DNA , Feminino , Citometria de Fluxo , Humanos , Células MCF-7
2.
J Enzyme Inhib Med Chem ; 34(1): 1481-1488, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31423846

RESUMO

Indoleamine 2,3-dioxygenase 1 (IDO1), a tryptophan catabolising enzyme, is known as a tumour cell survival factor that causes immune escape in several types of cancer. Flavonoids of Sophora flavescens have a variety of biological benefits for humans; however, cancer immunotherapy effect has not been fully investigated. The flavonoids (1-6) isolated from S. flavescens showed IDO1 inhibitory activities (IC50 4.3-31.4 µM). The representative flavonoids (4-6) of S. flavescens were determined to be non-competitive inhibitors of IDO1 by kinetic analyses. Their binding affinity to IDO1 was confirmed using thermal stability and surface plasmon resonance (SPR) assays. The molecular docking analysis and mutagenesis assay revealed the structural details of the interactions between the flavonoids (1-6) and IDO1. These results suggest that the flavonoids (1-6) of S. flavescens, especially kushenol E (6), as IDO1 inhibitors might be useful in the development of immunotherapeutic agents against cancers.


Assuntos
Antineoplásicos/farmacologia , Inibidores Enzimáticos/farmacologia , Flavonoides/farmacologia , Indolamina-Pirrol 2,3,-Dioxigenase/antagonistas & inibidores , Sophora/química , Antineoplásicos/química , Antineoplásicos/isolamento & purificação , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Inibidores Enzimáticos/química , Inibidores Enzimáticos/isolamento & purificação , Flavonoides/química , Flavonoides/isolamento & purificação , Células HeLa , Humanos , Indolamina-Pirrol 2,3,-Dioxigenase/genética , Indolamina-Pirrol 2,3,-Dioxigenase/metabolismo , Modelos Moleculares , Estrutura Molecular , Mutagênese Sítio-Dirigida , Relação Estrutura-Atividade , Células Tumorais Cultivadas
3.
Fitoterapia ; 137: 104260, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31284016

RESUMO

One new benzophenone derivative, named tenllone I (1), two new eremophilane derivatives lithocarins B (2) and C (3), and a new monoterpentoid lithocarin D (4), together with two know compounds (5 and 6) were isolated from the endophytic fungus Diaporthe lithocarpus A740. All of the structures for these new compounds were fully characterized and established on the basis of extensive spectroscopic interpretation. In addition, all the isolated compounds were evaluated in vitro for their cytotoxic activity. Compounds 2, 3, and 5 showed weak inhibitory activities against tumor cell lines.


Assuntos
Ascomicetos/química , Benzofenonas/isolamento & purificação , Antineoplásicos/isolamento & purificação , Antineoplásicos/farmacologia , Benzofenonas/farmacologia , Linhagem Celular Tumoral , China , Endófitos/química , Humanos , Estrutura Molecular , Morinda/microbiologia
4.
Fitoterapia ; 137: 104278, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31351910

RESUMO

Five new cytochalasans (1-5) were isolated from the rice fermentation of fungus Xylaria longipes, along with seven known compounds cytochalasin P (6), cytochalasin D (7), zygosporin D (8), 7-O-acetylcytochalasin D (9), cytochalasin C (10), 6,7-dihydro-7-oxo-cytochalasin C (11), and 6,7-dihydro-7-oxo-deacetylcytochalasin C (12). Their structures and absolute configurations were determined by extensive experimental spectroscopic methods as well as ECD calculation and GIAO 13C NMR calculation. The cytotoxicity of obtained compounds (1-12) was evaluated against human cancer cell lines HL-60, A549, SMMC-7721, MCF-7, and SW480. Compounds 6-8, 11, and 12 showed cytotoxicity with IC50 value ranging from 4.17-37.18 µM.


Assuntos
Antineoplásicos/farmacologia , Citocalasinas/farmacologia , Xylariales/química , Antineoplásicos/isolamento & purificação , Linhagem Celular Tumoral , China , Citocalasinas/isolamento & purificação , Humanos , Estrutura Molecular , Metabolismo Secundário
5.
Fitoterapia ; 137: 104253, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31271786

RESUMO

Nine new 19,20-epoxycytochalasans (1-9) were isolated from the rice fermentation extracts of endophytic fungus Xylaria cf. curta, along with four known compounds 19,20-epoxycytochalasin C (10), 18-desoxy-19,20-epoxycytochalasin C (11), 19,20-epoxycytochalasin D (12) and 5,6-dihydro-7-oxo-19,20-epoxycytochalasin C (13). Their structures and absolute configurations were determined by 1D and 2D NMR, HRESIMS, X-ray diffraction and ECD calculation. The cytotoxicity of obtained compounds (1-13) was evaluated against human cancer cell lines HL-60, A549, SMMC-7721, MCF-7, and SW480. Remarkably, compound 10 showed significant specific cytotoxicity against HL-60 cell lines with IC50 value of 1.11 µM.


Assuntos
Antineoplásicos/farmacologia , Citocalasinas/farmacologia , Xylariales/química , Antineoplásicos/isolamento & purificação , Linhagem Celular Tumoral , Citocalasinas/isolamento & purificação , Endófitos/química , Humanos , Estrutura Molecular
6.
Fitoterapia ; 137: 104257, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31278976

RESUMO

Two new meroditerpene pyrones, chevalone F (1) and 11-hydroxychevalone E (2), a new tryptoquivaline analog, tryptoquivaline V (3) and a new brasiliamide analog, brasiliamide G (4), together with thirteen known compounds, chevalones A-C (5-7), chevalone E (8), 11-hydroxychevalone C (9), pyripyropene A (10), isochaetominine C (11), pyrrolobenzoxazine terpenoids CJ-12662 (12) and CJ-12663 (13), fischerindoline (14), eurochevalierine (15), 1,4-diacetyl-2,5-dibenzylpiperazine-3,7''-oxide (16) and lecanorin (17) were isolated from the fungus Neosartorya pseudofischeri. Their structures were established on the basis of spectroscopic evidence. Compound 2 showed weak antibacterial activity against Escherichia coli and Salmonella enterica serovar Typhimurium, whereas compounds 7, 12, 13 and 15 showed antibacterial activity against Bacillus cereus and Staphylococcus aureus. In addition, compounds 13 and 14 showed cytotoxicity against KB and MCF-7 cancer cell lines, as well as the Vero cell line.


Assuntos
Antibacterianos/farmacologia , Antineoplásicos/farmacologia , Indóis/farmacologia , Neosartorya/química , Pironas/farmacologia , Animais , Antibacterianos/isolamento & purificação , Antineoplásicos/isolamento & purificação , Cercopithecus aethiops , Florestas , Humanos , Indóis/isolamento & purificação , Células KB , Células MCF-7 , Estrutura Molecular , Pironas/isolamento & purificação , Microbiologia do Solo , Tailândia , Células Vero
7.
J Cancer Res Clin Oncol ; 145(8): 1949-1976, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31292714

RESUMO

PURPOSE: Efflux transporters of the adenosine triphosphate-binding cassette (ABC)-superfamily play an important role in the development of multidrug resistance (multidrug resistant; MDR) in cancer. The overexpression of these transporters can directly contribute to the failure of chemotherapeutic drugs. Several in vitro and in vivo models exist to screen for the efficacy of chemotherapeutic drugs against MDR cancer, specifically facilitated by efflux transporters. RESULTS: This article reviews a range of efflux transporter-based MDR models used to test the efficacy of compounds to overcome MDR in cancer. These models are classified as either in vitro or in vivo and are further categorised as the most basic, conventional models or more complex and advanced systems. Each model's origin, advantages and limitations, as well as specific efflux transporter-based MDR applications are discussed. Accordingly, future modifications to existing models or new research approaches are suggested to develop prototypes that closely resemble the true nature of multidrug resistant cancer in the human body. CONCLUSIONS: It is evident from this review that a combination of both in vitro and in vivo preclinical models can provide a better understanding of cancer itself, than using a single model only. However, there is still a clear lack of progression of these models from basic research to high-throughput clinical practice.


Assuntos
Transportadores de Cassetes de Ligação de ATP/fisiologia , Antineoplásicos/isolamento & purificação , Resistência a Múltiplos Medicamentos , Resistencia a Medicamentos Antineoplásicos , Ensaios de Seleção de Medicamentos Antitumorais/métodos , Modelos Biológicos , Transportadores de Cassetes de Ligação de ATP/antagonistas & inibidores , Transportadores de Cassetes de Ligação de ATP/genética , Antineoplásicos/farmacologia , Transporte Biológico/efeitos dos fármacos , Transporte Biológico/genética , Técnicas de Cultura/métodos , Técnicas de Apoio para a Decisão , Resistência a Múltiplos Medicamentos/efeitos dos fármacos , Resistência a Múltiplos Medicamentos/genética , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/genética , Humanos , Especificidade de Órgãos , Seleção de Pacientes
8.
J Agric Food Chem ; 67(32): 8855-8867, 2019 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-31343893

RESUMO

Abalone (Haliotis discus hannai) is a precious seafood in the market. It has been reported that biological active substances derived from abalone have anti-oxidative, anti-inflammatory, anti-bacterial, and anti-thrombosis potential. However, there were few studies to assess whether they have anti-cancer potential. In this study, we evaluated the anti-metastasis and anti-pro-angiogenic factors and mechanism of action of boiled abalone byproduct peptide (BABP, EMDEAQDPSEW) in human fibrosarcoma (HT1080) cells and human umbilical vein endothelial cells (HUVECs). The results demonstrated that BABP treatment significantly lowers migration and the invasion of HT1080 cells and HUVECs. BABP inhibits phorbol 12-myristate 13-acetate (PMA)-induced matrix metalloproteinase (MMP) expression and activity by blocking mitogen-activated protein kinases (MAPKs) and NF-κB signaling and hypoxia-induced vascular endothelial growth factor (VEGF) secretion and hypoxia inducible factor (HIF)-1α accumulation through suppressing the AKT/mTOR signal pathway. BABP treatment inhibits VEGF-induced VEGFR-2 expression and tube formation in HUVECs. The effect of BABP on anti-metastatic and anti-vascular activity in HT1080 cells and HUVECs revealed that BABP may be a potential pharmacophore for tumor therapy in the future.


Assuntos
Inibidores da Angiogênese/farmacologia , Antineoplásicos/farmacologia , Gastrópodes/química , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Peptídeos/farmacologia , Resíduos/análise , Inibidores da Angiogênese/química , Inibidores da Angiogênese/isolamento & purificação , Animais , Antineoplásicos/química , Antineoplásicos/isolamento & purificação , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Metaloproteinase 2 da Matriz/genética , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/genética , Metaloproteinase 9 da Matriz/metabolismo , Metástase Neoplásica , Neovascularização Patológica/tratamento farmacológico , Neovascularização Patológica/genética , Neovascularização Patológica/metabolismo , Neovascularização Patológica/fisiopatologia , Peptídeos/química , Peptídeos/isolamento & purificação , Frutos do Mar/análise , Fator A de Crescimento do Endotélio Vascular/genética , Fator A de Crescimento do Endotélio Vascular/metabolismo , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/genética , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/metabolismo
9.
Chem Pharm Bull (Tokyo) ; 67(7): 666-674, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31257322

RESUMO

Dimeric sesquiterpene thioalkaloids from the rhizomes of Nuphar pumilum exhibited immunosuppressive effects using a sheep erythrocyte plaque forming cell (PFC) assay, as well as an anti-metastasis effect, and rapid apoptosis-inducing effects in tumor cell lines. In particular, dimeric sesquiterpene thioalkaloids with a hydroxy group (6-hydroxythiobinupharidine, 6,6'-dihydroxythiobinupharidine, 6-hydroxythionuphlutine B) showed substantial effects, whereas dimeric sesquiterpene thioalkaloids lacking the hydroxy group (thiobinupharidine, thionuphlutine B, 6'-hydroxythionuphlutine B, neothiobinupharidine, thionuphlutine B ß-sulfoxide, neothiobinupharidine ß-sulfoxide) and monomeric sesquiterpene alkaloids (nupharidine, 7-epideoxynupharidine, nupharolutine) showed weak activity. In this review, we summarize our studies of the biofunctional effects of these alkaloids.


Assuntos
Alcaloides/química , Nuphar/química , Sesquiterpenos/química , Alcaloides/isolamento & purificação , Alcaloides/farmacologia , Animais , Antineoplásicos/química , Antineoplásicos/isolamento & purificação , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Eritrócitos/citologia , Eritrócitos/efeitos dos fármacos , Eritrócitos/metabolismo , Humanos , Imunossupressores/química , Imunossupressores/isolamento & purificação , Imunossupressores/farmacologia , Nuphar/metabolismo
10.
Fitoterapia ; 137: 104194, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31175954

RESUMO

Four unusual heterodimeric tetrahydroxanthones, usneaxanthones A-D (1-4) were isolated from lichen Usnea aciculifera Vain (Parmeliaceae). Their structures and absolute configurations, particularly the central and axial chiralities, were unambiguously demonstrated by a combination of spectroscopic data (1D, 2D NMR, HRESIMS), electronic circular dichroism (ECD) experiments, and single-crystal X-ray crystallographic analyses. Cytotoxic effects of isolated compounds (1, 2 and 4) were evaluated on HT-29 human colorectal cancer cells. Compound 4 showed potent cytotoxicity against HT-29 with IC50 values of 2.41 µM.


Assuntos
Antineoplásicos/farmacologia , Usnea/química , Xantonas/farmacologia , Antineoplásicos/isolamento & purificação , Células HT29 , Humanos , Estrutura Molecular , Vietnã , Xantonas/isolamento & purificação
11.
Food Chem Toxicol ; 131: 110563, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31199992

RESUMO

Apple pomace (AP) utilised for analysis of triterpenic acids (TTAs) using HPLC-MS/MS. The methanol, ethanol and ethyl acetate extracts showed high phenolic content with significant antioxidant activity compared to chloroform and n-hexane. AP TTAs; ursolic acid, betulinic acid and maslinic acid showed potent antioxidant and enzyme inhibitory effects. The IC50 values were 13.2-30.8 µg/mL (tyrosinase), 19.6-42.5 µg/mL (xanthine oxidase) and 16.6-38.6 µg/mL (urease) for AP extracts and 8.4-25.8 µg/mL (tyrosinase), 12.6-30.2 µg/mL (xanthine oxidase) and 10.1-28.6 µg/mL (urease) for TTAs, compared to the positive controls; kojic acid (10.4 ±â€¯0.06 µg/mL), allopurinol (9.6 ±â€¯0.04 µg/mL) and thiourea (8.9 ±â€¯0.02 µg/mL) towards respective enzymes. UA showed a competitive type of inhibition for tyrosinase, while BA showed a noncompetitive type of inhibition towards xanthine oxidase. In addition, the AP extracts and TTAs exerted significant cytotoxic effects towards the proliferation of cancer cell lines. AP methanol extract (IC50 of 38.5 ±â€¯4.1, 47.1 ±â€¯3.5, 70.6 ±â€¯2.3, and 50.5 ±â€¯3.9 µg/mL) and ursolic acid (IC50 of 6.5 ±â€¯0.7, 15.5 ±â€¯1.4, 20.8 ±â€¯1.3, and 5.6 ±â€¯0.8 µg/mL) showed prominent anticancer activity on Hela, Skov-3, Caski, and NCL cancer cell lines, respectively. Thus, this study shows that the AP & TTAs could be utilized for functional food development and as a potent antioxidant, anticancer, skin whitening, and anti-urolithic agents.


Assuntos
Antineoplásicos/farmacologia , Inibidores Enzimáticos/farmacologia , Depuradores de Radicais Livres/farmacologia , Frutas/química , Malus/química , Triterpenos/farmacologia , Animais , Antineoplásicos/química , Antineoplásicos/isolamento & purificação , Linhagem Celular Tumoral , Cães , Ensaios Enzimáticos , Inibidores Enzimáticos/química , Inibidores Enzimáticos/isolamento & purificação , Depuradores de Radicais Livres/química , Depuradores de Radicais Livres/isolamento & purificação , Humanos , Células Madin Darby de Rim Canino , Monofenol Mono-Oxigenase/antagonistas & inibidores , Extratos Vegetais/análise , Extratos Vegetais/química , Extração em Fase Sólida , Triterpenos/química , Triterpenos/isolamento & purificação , Urease/antagonistas & inibidores , Xantina Oxidase/antagonistas & inibidores
12.
BMC Complement Altern Med ; 19(1): 142, 2019 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-31221160

RESUMO

BACKGROUND: Microbial species in the brine pools of the Red Sea and the brine pool-seawater interfaces are exposed to high temperature, high salinity, low oxygen levels and high concentrations of heavy metals. As adaptations to these harsh conditions require a large suite of secondary metabolites, these microbes have a huge potential as a source of novel anticancer molecules. METHODS: A total of 60 ethyl-acetate extracts of newly isolated strains from extreme environments of the Red-Sea were isolated and tested against several human cancer cell lines for potential cytotoxic and apoptotic activities. RESULTS: Isolates from the Erba brine-pool accounted for 50% of active bacterial extracts capable of inducing 30% or greater inhibition of cell growth. Among the 60 extracts screened, seven showed selectivity towards triple negative BT20 cells compared to normal fibroblasts. CONCLUSION: In this study, we identified several extracts able to induce caspase-dependent apoptosis in various cancer cell lines. Further investigations and isolation of the active compounds of these Red Sea brine pool microbes may offer a chemotherapeutic potential for cancers with limited treatment options.


Assuntos
Antineoplásicos/farmacologia , Bactérias/química , Microbiota , Sais/química , Água do Mar/microbiologia , Antineoplásicos/isolamento & purificação , Apoptose/efeitos dos fármacos , Bactérias/classificação , Bactérias/genética , Bactérias/isolamento & purificação , Linhagem Celular Tumoral , Humanos , Oceano Índico
13.
Phytochemistry ; 164: 154-161, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31151062

RESUMO

Oxytropiols A-J, ten undescribed guaiane-type sesquiterpenoids, and the mycotoxin swainsonine (SW) were isolated from the locoweed endophytic fungus Alternaria oxytropis. The chemical structures of these sesquiterpenoids were elucidated on the basis of HR-ESI-MS and NMR data including 1H, 13C, HSQC, 1H-1H COSY, HMBC, and NOESY spectra, and the absolute configurations of these compounds were determined using a modified Mosher's method and X-ray diffraction spectroscopy. A possible biosynthetic pathway of these guaiane-type sesquiterpenoids is discussed, and proposed that post-modification oxidative enzymes might form these highly polyhydroxylated structures. Compound 1 displayed biological effects on the root growth of Arabidopsis thaliana, and SW displayed cytotoxicity against A549 and HeLa cancer cell lines.


Assuntos
Alternaria/química , Antineoplásicos/farmacologia , Micotoxinas/farmacologia , Sesquiterpenos/farmacologia , Swainsonina/farmacologia , Células A549 , Antineoplásicos/química , Antineoplásicos/isolamento & purificação , Proliferação de Células/efeitos dos fármacos , Cristalografia por Raios X , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Células HeLa , Humanos , Modelos Moleculares , Conformação Molecular , Micotoxinas/química , Micotoxinas/isolamento & purificação , Sesquiterpenos/química , Sesquiterpenos/isolamento & purificação , Relação Estrutura-Atividade , Swainsonina/química , Swainsonina/isolamento & purificação
14.
Curr Top Med Chem ; 19(15): 1318-1337, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31215379

RESUMO

Breast cancer is the most common cancer suffered by female, and the second highest cause of cancer-related death among women worldwide. At present, hormone therapy is still the main treatment route and can be divided into three main categories: selective estrogen receptor modulators (SERMs), selective estrogen receptor downregulators (SERDs), and aromatase inhibitors (AIs). However, breast cancer is difficult to cure even after several rounds of anti-estrogen therapy and most drugs have serious side-effects. Here, we review the literature published over the past five years regarding the isolation and synthesis of analogs and their derivatives.


Assuntos
Antineoplásicos/farmacologia , Inibidores da Aromatase/farmacologia , Neoplasias da Mama/tratamento farmacológico , Antagonistas do Receptor de Estrogênio/farmacologia , Moduladores de Receptor Estrogênico/farmacologia , Receptor alfa de Estrogênio/antagonistas & inibidores , Animais , Antineoplásicos/química , Antineoplásicos/isolamento & purificação , Inibidores da Aromatase/química , Inibidores da Aromatase/isolamento & purificação , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Proliferação de Células/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Antagonistas do Receptor de Estrogênio/química , Antagonistas do Receptor de Estrogênio/isolamento & purificação , Moduladores de Receptor Estrogênico/química , Moduladores de Receptor Estrogênico/isolamento & purificação , Receptor alfa de Estrogênio/metabolismo , Feminino , Humanos , Estrutura Molecular
15.
Mar Drugs ; 17(6)2019 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-31163640

RESUMO

Ovarian cancer is one of the prevalent gynecological cancers occurring in women. In particular, the efficiency of standard therapeutic methods decreases when recurrence and chemoresistance ensue. To assist standard anti-cancer agents in the cure of ovarian cancer, development and application of new compounds such as small molecules or natural products are required. Gentisyl alcohol is one of the secondary metabolites that can be obtained by purification from bacteria or fungi and is known to have antibacterial, antifungal, antiviral, and anti-cancer effects. In the present study, we verified the effect of gentisyl alcohol derived from marine Arthrinium sp. on suppressing proliferation and inducing apoptosis via DNA fragmentation in human ovarian cancers cells (ES2 and OV90 cells). We also confirmed that there was an accumulation of sub-G1 cells and a loss of mitochondrial membrane potential with calcium dysregulation in gentisyl alcohol-treated ovarian cancer cells. Moreover, gentisyl alcohol up-regulated signal transduction of MAPK and PI3K/AKT pathways. Collectively, our results demonstrated the possibility of gentisyl alcohol as a novel therapeutic agent for human ovarian cancer.


Assuntos
Apoptose/efeitos dos fármacos , Ascomicetos/química , Álcoois Benzílicos/farmacologia , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Antineoplásicos/química , Antineoplásicos/isolamento & purificação , Antineoplásicos/farmacologia , Ascomicetos/metabolismo , Álcoois Benzílicos/química , Álcoois Benzílicos/isolamento & purificação , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Humanos , Sistema de Sinalização das MAP Quinases/genética , Fosfatidilinositol 3-Quinases/genética , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo
16.
Eur J Med Chem ; 176: 513-533, 2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31151068

RESUMO

From times immemorial, natural products have played an important role in the management of human health. Andrographis paniculata, belonging to the family Acanthaceae and its constituents are reported to possess a wide range of biological properties such as anti-cancer, anti-diabetic, anti-inflammatory, anti-bacterial, anti-malarial, anti-hepatitis, anti-HIV, anti-atherosclerosis, hepatoprotective, FXR antagonist, and α-glucosidase inhibition. Andrographolide (1), is identified as the major bioactive constituent of the plant. Promising biological properties of the major constituent Andrographolide (1) along with structural amenability for facile semi-synthetic modifications have led to the generation of structurally diverse bioactive labdane diterpenes by several research groups. The promising biological activities exhibited by these semi-synthetic derivatives have further kindled interest and the continued research is evidenced through publications, patents and could possibly lead to the development of Andrographolide based medicines in future. The present review aims at compiling and discussing various semi-synthetic derivatives of Andrographolide in relation to their biological properties and their mechanisms of action.


Assuntos
Diterpenos/farmacologia , Andrographis/química , Animais , Antineoplásicos/síntese química , Antineoplásicos/isolamento & purificação , Antineoplásicos/farmacocinética , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Diterpenos/síntese química , Diterpenos/isolamento & purificação , Diterpenos/farmacocinética , Humanos
17.
Carbohydr Polym ; 216: 204-212, 2019 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-31047058

RESUMO

Sulfated polysaccharides (SPSs) are polysaccharides (PSs) with high sulfate functionalization and possess bioactivities. This study aimed to increase the sulfate content of SPSs in Antrodia cinnamomea through sulfate feeding. Feeding A. cinnamomea with sodium thiosulfate was found to increase yields of PSs and SPSs in A. cinnamomea. The SPSs thus obtained (ST-SPS) were further isolated, showing enhanced sulfate content of 2.5 mmol/g. Sodium thiosulfate induced changes in molecular weight from 320 kDa to 1342 kDa, and area percentage of low-molecular-weight ST-SPS (< 20 kDa) was decreased. Functional studies revealed that sodium thiosulfate increased the ST-SPS anticancer efficacy in cancer cells via inhibition of EGFR/AKT signaling. Moreover, the ST-SPS enhanced synergistically cisplatin-, gefitinib- and 5 FU-induced cytotoxic effects in lung cancer H1975 cells and colon cancer CT26 cells. This study is the first to demonstrate that sodium thiosulfate induced changes in properties of A. cinnamomea with the anticancer mechanisms of ST-SPS.


Assuntos
Antineoplásicos/farmacologia , Antrodia/química , Antrodia/metabolismo , Polissacarídeos/farmacologia , Ésteres do Ácido Sulfúrico/farmacologia , Tiossulfatos/metabolismo , Animais , Antineoplásicos/química , Antineoplásicos/isolamento & purificação , Antineoplásicos/metabolismo , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Cisplatino/farmacologia , Sinergismo Farmacológico , Receptores ErbB/metabolismo , Fluoruracila/farmacologia , Gefitinibe/farmacologia , Humanos , Concentração Inibidora 50 , Camundongos , Peso Molecular , Fosforilação/efeitos dos fármacos , Polissacarídeos/biossíntese , Polissacarídeos/química , Polissacarídeos/isolamento & purificação , Transdução de Sinais/efeitos dos fármacos , Ésteres do Ácido Sulfúrico/química , Ésteres do Ácido Sulfúrico/isolamento & purificação , Ésteres do Ácido Sulfúrico/metabolismo
18.
Molecules ; 24(9)2019 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-31052167

RESUMO

Cyclooxygenase-2 (COX-2) as a rate-limiting metabolism enzyme of arachidonic acid has been found to be implicated in tumor occurrence, angiogenesis, metastasis as well as apoptosis inhibition, regarded as an attractive therapeutic target for cancer therapy. In our research, a series of dihydropyrazole derivatives containing benzo oxygen heterocycle and sulfonamide moieties were designed as highly potent and selective COX-2 inhibitors by computer-aided drug analysis of known COX-2 inhibitors. A total of 26 compounds were synthesized and evaluated COX-2 inhibition and pharmacological efficiency both in vitro and in vivo with multi-angle of view. Among them, compound 4b exhibited most excellent anti-proliferation activities against SW620 cells with IC50 of 0.86 ± 0.02 µM than Celecoxib (IC50 = 1.29 ± 0.04 µM). The results favored our rational design intention and provides compound 4b as an effective COX-2 inhibitor available for the development of colon tumor therapeutics.


Assuntos
Inibidores de Ciclo-Oxigenase 2/química , Inibidores de Ciclo-Oxigenase 2/farmacologia , Desenho de Drogas , Oxigênio/química , Pirazóis/química , Pirazóis/farmacologia , Sulfonamidas/química , Animais , Antineoplásicos/química , Antineoplásicos/isolamento & purificação , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Adesão Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Neoplasias do Colo , Inibidores de Ciclo-Oxigenase 2/síntese química , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Humanos , Camundongos , Conformação Molecular , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Estrutura Molecular , Pirazóis/síntese química , Relação Quantitativa Estrutura-Atividade , Ensaios Antitumorais Modelo de Xenoenxerto
19.
Mar Drugs ; 17(5)2019 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-31096582

RESUMO

The marine-sourced fungus Penicillium sp. ZZ380 was previously reported to have the ability to produce a series of new pyrrospirone alkaloids. Further investigation on this strain resulted in the isolation and identification of novel penicipyrroether A and pyrrospirone J. Each of them represents the first example of its structural type, with a unique 6/5/6/5 polycyclic fusion that is different from the 6/5/6/6 fused ring system for the reported pyrrospirones. Their structures were elucidated by extensive nuclear magnetic resonance (NMR) and high resolution electrospray ionization mass spectroscopy (HRESIMS) spectroscopic analyses, electronic circular dichroism (ECD) and 13C NMR calculations and X-ray single crystal diffraction. Penicipyrroether A showed potent antiproliferative activity against human glioma U87MG and U251 cells with half maximal inhibitory concentration (IC50) values of 1.64-5.50 µM and antibacterial inhibitory activity with minimum inhibitory concentration (MIC) values of 1.7 µg/mL against methicillin-resistant Staphylococcus aureus and 3.0 µg/mL against Escherichia coli.


Assuntos
Proliferação de Células/efeitos dos fármacos , Escherichia coli/efeitos dos fármacos , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Penicillium/química , Antibacterianos/química , Antibacterianos/isolamento & purificação , Antibacterianos/farmacologia , Antineoplásicos/química , Antineoplásicos/isolamento & purificação , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Dicroísmo Circular , Cristalografia por Raios X , Humanos , Concentração Inibidora 50 , Espectroscopia de Ressonância Magnética , Espectrometria de Massas , Testes de Sensibilidade Microbiana
20.
Mar Drugs ; 17(5)2019 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-31108876

RESUMO

The mangrove ecosystem is a rich resource for the discovery of actinomycetes with potential applications in pharmaceutical science. Besides the genus Streptomyces, Micromonospora is also a source of new bioactive agents. We screened Micromonospora from the rhizosphere soil of mangrove plants in Fujian province, China, and 51 strains were obtained. Among them, the extracts of 12 isolates inhibited the growth of human lung carcinoma A549 cells. Strain 110B exhibited better cytotoxic activity, and its bioactive constituents were investigated. Consequently, three new isoflavonoid glycosides, daidzein-4'-(2-deoxy-α-l-fucopyranoside) (1), daidzein-7-(2-deoxy-α-l-fucopyranoside) (2), and daidzein-4',7-di-(2-deoxy-α-l-fucopyranoside) (3) were isolated from the fermentation broth of strain 110B. The structures of the new compounds were determined by spectroscopic methods, including 1D and 2D nuclear magnetic resonance (NMR) and high-resolution electrospray ionization mass spectrometry (HR-ESIMS). The result of medium-changing experiments implicated that these new compounds were microbial biotransformation products of strain M. aurantiaca 110B. The three compounds displayed moderate cytotoxic activity to the human lung carcinoma cell line A549, hepatocellular liver carcinoma cell line HepG2, and the human colon tumor cell line HCT116, whereas none of them showed antifungal or antibacterial activities.


Assuntos
Sobrevivência Celular/efeitos dos fármacos , Micromonospora/química , Células A549 , Antineoplásicos/química , Antineoplásicos/isolamento & purificação , Antineoplásicos/farmacologia , Glicosídeos/química , Glicosídeos/isolamento & purificação , Glicosídeos/farmacologia , Células HCT116 , Células Hep G2 , Humanos , Isoflavonas/química , Microbiologia do Solo
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