RESUMO
Pinostrobin demonstrated anticancer properties, but its hydrophobic feature led to a reduction in bioavailability. The mitochondria-targeted approach successfully synthesized eight new alkyl triphenylphosphonium pinostrobin derivatives (1-8) with good yield in this study. Seven compounds (1-3, 5-8) showed greater cytotoxic potency against the human MCF-7 breast cancer cell line than pinostrobin. Molecular docking studies were performed with two important targets in hormone-dependent anticancer strategies, estrogen receptor α (ERα) ligand binding domains, 3ERT (antagonist recognition and antiproliferative function), and 1GWR (agonist recognition and pro-proliferative function). In addition, the MD simulation study of the two most potent compounds (2 and 3) complexed with both ERα forms suggested that compounds 2 and 3 could serve as favourable antagonists. Furthermore, the in silico ADMET prediction indicated that compounds 2 and 3 could be potential drug candidates.
Assuntos
Antineoplásicos , Neoplasias da Mama , Proliferação de Células , Ensaios de Seleção de Medicamentos Antitumorais , Simulação de Acoplamento Molecular , Compostos Organofosforados , Humanos , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/síntese química , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Neoplasias da Mama/metabolismo , Proliferação de Células/efeitos dos fármacos , Compostos Organofosforados/química , Compostos Organofosforados/farmacologia , Compostos Organofosforados/síntese química , Relação Estrutura-Atividade , Células MCF-7 , Receptor alfa de Estrogênio/metabolismo , Receptor alfa de Estrogênio/antagonistas & inibidores , Feminino , Descoberta de Drogas , Estrutura Molecular , Relação Dose-Resposta a Droga , FlavanonasRESUMO
Persisting inflammation has been discovered in lungs and other parenchymatous organs of some COVID-19 convalescents. Calprotectin, neutrophil extracellular traps (NETs), syndecan-1 and neopterin are general key inflammatory markers, and systemically enhanced levels of them may remain after the COVID-19 infection. These inflammatory markers were therefore measured in serum samples of 129 COVID-19 convalescent and 27 healthy blood donors or employees at Oslo Blood bank, Norway. Also antibodies against SARS-CoV-2 nucleocapsid antigen were measured, and timing of sampling and severity of infection noted. Whereas neopterin and NETs values remained low and those for syndecan-1 were not raised to statistically significant level, concentrations for calprotectin, as measured by a novel mixed monoclonal assay, were significantly increased in the convalescents. Antibodies against SARS-CoV-2 nucleocapsid antigen were elevated, but did not correlate with levels of inflammatory markers. Difference between the groups in only one biomarker makes evaluation of ongoing or residual inflammation in the convalescents difficult. If there is a low-grade inflammation, it would in that case involve neutrophils.
Assuntos
COVID-19 , Armadilhas Extracelulares , Biomarcadores , Doadores de Sangue , COVID-19/diagnóstico , Humanos , Inflamação/diagnóstico , Complexo Antígeno L1 Leucocitário , Neopterina , SARS-CoV-2 , Sindecana-1RESUMO
From a CH2 Cl2 -soluble fraction of the stem barks of Taxus wallichiana, one new abeo-icetexane-type diterpenoid, taxamairinâ I (1), was isolated. Its absolute configuration was elucidated based on spectroscopic interpretation and time-dependent density functional theory (TD-DFT) calculation of optical rotation. In addition, the plausible biosynthesis pathway for the formation of the new abeo-icetexane-type diterpenoid was proposed. Taxamairinâ I (1), at a concentration of 100â µM, did not show cytotoxicity against Hep3B human liver cancer cell lines.
Assuntos
Diterpenos , Taxus , Humanos , Linhagem Celular , Diterpenos/farmacologia , Diterpenos/metabolismo , Taxus/químicaRESUMO
Tumor necrosis factor α (TNF-α), a pro-inflammatory cytokine, regulates inflammatory and immune responses by up-regulating gene expression in a manner that is dependent on the transcription factor nuclear factor κB (NF-κB). In the present study, we found that 4-hydroxypanduratin A and isopanduratin A, constituents of the rhizomes of Boesenbergia pandurata, inhibited the TNF-α-stimulated up-regulation of intercellular adhesion molecule-1 (ICAM-1) in human lung adenocarcinoma A549 cells. 4-Hydroxypanduratin A and isopanduratin A also reduced ICAM-1 mRNA expression and NF-κB-responsive luciferase activity in TNF-α-stimulated A549 cells. Moreover, 4-hydroxypanduratin A and isopanduratin A prevented the TNF-α-stimulated translocation of the NF-κB subunit p65 to the nucleus and the phosphorylation and proteasomal degradation of the inhibitor of the NF-κB α protein. The present results revealed that 4-hydroxypanduratin A and isopanduratin A inhibit TNF-α-stimulated gene expression and the NF-κB-dependent signaling pathway in A549 cells.
Assuntos
Adenocarcinoma de Pulmão/metabolismo , Chalconas/farmacologia , Neoplasias Pulmonares/metabolismo , NF-kappa B/metabolismo , Extratos Vegetais/farmacologia , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Células A549 , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/fisiologia , Relação Dose-Resposta a Droga , Regulação Neoplásica da Expressão Gênica , Humanos , Molécula 1 de Adesão Intercelular/biossíntese , Molécula 1 de Adesão Intercelular/genética , NF-kappa B/antagonistas & inibidores , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/fisiologia , Fator de Necrose Tumoral alfa/toxicidadeRESUMO
Human pancreatic cancer cell lines have a remarkable tolerance to nutrition starvation, which enables them to survive under a tumor microenvironment. The search for agents that preferentially inhibit the survival of cancer cells under low nutrient conditions represents a novel antiausterity strategy in anticancer drug discovery. In this investigation, a methanol extract of the rhizomes of Boesenbergia pandurata showed potent preferential cytotoxicity against PANC-1 human pancreatic cancer cells under nutrient-deprived conditions, with a PC50 value of 6.6 µg/mL. Phytochemical investigation of this extract led to the isolation of 15 compounds, including eight new cyclohexene chalcones (1-8). The structures of the new compounds were elucidated by NMR spectroscopic data analysis. Among the isolated compounds obtained, isopanduratin A1 (14) and nicolaioidesin C (15) exhibited potent preferential cytotoxicity against PANC-1 human pancreatic cancer cells under nutrition-deprived conditions, with PC50 values of 1.0 and 0.84 µM, respectively.
Assuntos
Antineoplásicos Fitogênicos/isolamento & purificação , Chalcona/isolamento & purificação , Chalcona/farmacologia , Chalconas/química , Cicloexanos/isolamento & purificação , Cicloexanos/farmacologia , Neoplasias Pancreáticas/tratamento farmacológico , Extratos Vegetais/química , Rizoma/química , Zingiberaceae/química , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/farmacologia , Linhagem Celular Tumoral , Chalcona/química , Chalconas/isolamento & purificação , Chalconas/farmacologia , Cicloexanos/química , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Estrutura MolecularRESUMO
From a CH2Cl2 extract of the bark of Taxus wallichiana, six new taxoids, wallitaxanes A-F (1-6), were isolated, together with 29 known compounds. The structures of the new compounds were elucidated on the basis of spectroscopic data interpretation. Wallitaxane D (4) was identified as an opened oxetane-type taxoid having the first naturally occurring C(H)-20 acetal group, while wallitaxanes E (5) and F (6) are representative of the rare abeo-taxoid class. The isolated compounds were evaluated for their α-glucosidase inhibitory activity and for cytotoxicity against the HeLa human cervical cancer cell line. In the present work, taxanes were found to exhibit α-glucosidase inhibitory activity for the first time, and wallitaxane A (1) showed the most potent effect, with an IC50 value of 3.6 µM. In turn, 7-epi-taxol (16) and 7-epi-10-deacetyltaxol (17) showed IC50 values of 0.05 and 0.085 nM, respectively, against HeLa cells.
Assuntos
Antineoplásicos Fitogênicos/isolamento & purificação , Hidrocarbonetos Aromáticos com Pontes/química , Diterpenos/isolamento & purificação , Diterpenos/farmacologia , Inibidores de Glicosídeo Hidrolases/isolamento & purificação , Inibidores de Glicosídeo Hidrolases/farmacologia , Casca de Planta/química , Taxoides/isolamento & purificação , Taxoides/farmacologia , Taxus/química , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/farmacologia , Diterpenos/química , Inibidores de Glicosídeo Hidrolases/química , Humanos , Estrutura Molecular , Paclitaxel/farmacologia , Taxoides/química , alfa-GlucosidasesRESUMO
Human pancreatic cancer cell lines such as PANC-1 have an altered metabolism, enabiling them to tolerate and survive under extreme conditions of nutrient starvation. The search for candidates that inhibit their viability during nutrition starvation represents a novel antiausterity strategy in anticancer drug discovery. A methanol extract of the bark of Mangifera indica was found to inhibit the survival of PANC-1 human pancreatic cancer cells preferentially under nutrient-deprived conditions with a PC50 value of 15.5 µg/mL, without apparent toxicity, in normal nutrient-rich conditions. Chemical investigation on this bioactive extract led to the isolation of 19 compounds (1-19), including two new cycloartane-type triterpenes, mangiferolate A (1) and mangiferolate B (2). The structures of 1 and 2 were determined by NMR spectroscopic analysis. Among the isolated compounds, mangiferolate B (2) and isoambolic acid (12) exhibited potent preferential cytotoxicity against PANC-1 human pancreatic cancer cells under the nutrition-deprived condition with PC50 values of 11.0 and 4.8 µM, respectively.
Assuntos
Antineoplásicos Fitogênicos/isolamento & purificação , Antineoplásicos Fitogênicos/farmacologia , Mangifera/química , Neoplasias Pancreáticas/tratamento farmacológico , Triterpenos/isolamento & purificação , Triterpenos/farmacologia , Antineoplásicos Fitogênicos/química , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular , Casca de Planta/química , Triterpenos/química , VietnãRESUMO
Human pancreatic cancer cell lines have remarkable tolerance to nutrition starvation, which enables them to survive under a tumor microenvironment. The search for agents that preferentially inhibit the survival of cancer cells under low nutrient conditions is a novel antiausterity strategy in anticancer drug discovery. In this study, the methanolic extract of the leaves of Artocarpus altilis showed 100â% preferential cytotoxicity against PANC-1 human pancreatic cancer cells under nutrient-deprived conditions at a concentration of 50 µg/mL. Further investigation of this extract led to the isolation of eight new geranylated dihydrochalcones named sakenins A-H (1-8) together with four known compounds (9-12). Among them, sakenins F (6) and H (8) were identified as potent preferentially cytotoxic candidates with PC50 values of 8.0 µM and 11.1 µM, respectively.
Assuntos
Artocarpus/química , Chalconas/farmacologia , Citotoxinas/farmacologia , Extratos Vegetais/farmacologia , Linhagem Celular Tumoral , Citotoxinas/química , Citotoxinas/isolamento & purificação , Humanos , Ressonância Magnética Nuclear Biomolecular , Neoplasias Pancreáticas/patologia , Fitoterapia , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Microambiente TumoralRESUMO
From the ethyl acetate extract of the stems of Embelia ribes (Myrsinaceae), a new alkenylresorcinol, embeliphenol A (1), together with 11 known compounds have been isolated. Their structures were elucidated on the basis of spectroscopic data. All compounds possessed significant α-glucosidase inhibitory activity in a concentration-dependent manner, except for 2 and 9. Compounds 1, 3-6, 8, and 12 showed more potent inhibitory activity, with IC50 values ranging from 10.4 to 116.7 µM, than that of a positive control acarbose (IC50 , 214.5 µM).
Assuntos
Embelia/química , Inibidores de Glicosídeo Hidrolases/química , Extratos Vegetais/química , Caules de Planta/química , Resorcinóis/química , Inibidores de Glicosídeo Hidrolases/isolamento & purificação , Estrutura Molecular , Resorcinóis/isolamento & purificaçãoRESUMO
Plants of the Zingiberaceae family, specifically those belonging to the Curcuma species, are commonly under consideration as potential therapeutic agents for the management of gastrointestinal diseases. In this study, we carried out a phytochemical study on Curcuma aromatica Salisb. (or so-called "Nghe trang" in Vietnamese) grown in Vietnam, which yields three newly discovered 3,5-diacetoxy diarylheptanoids (1-3) and six known 3,5-dihydroxyl diarylheptanoids (4-9). The bioactivity assessment shows that all isolated compounds, except compounds 3, 7, and 8, could inhibit urease. Compounds 4 and 9 significantly inhibit urease, with an IC50 value of 9.6 and 21.4 µM, respectively, more substantial than the positive control, hydroxyurea (IC50 = 77.4 µM). The structure-activity relationship (SAR) of linear diarylheptanoids was also established, suggesting that the hydroxyl groups at any position of skeleton diarylheptanoids are essential for exerting anti-urease action. Through a comparative analysis of the binding sites of hydroxyurea and diarylheptanoid compounds via our constructed in silico model, the mechanism of action of diarylheptanoid compounds is predicted to bind to the dynamic region close to the dinickel active center, resulting in a loss of catalytic activity. Such insights certainly help design and/or find diarylheptanoid-based compounds for treating gastric ulcers through inhibiting urease.
RESUMO
From the EtOAc extract of the wood of the stems of Taxotrophis ilicifolius (Moraceae), two new secondary metabolites, named taxotrophises A (1) and B (2), were isolated, together with five known compounds (3-7). Their chemical structures have been elucidated by extensive NMR spectroscopic analysis. All isolated compounds have been evaluated for α-glucosidase inhibitory activity. In the present work, compounds 1 and 4 showed the strongest α-glucosidase inhibitory activity with IC50 values of 6.5 and 1.5 µM, respectively, and stronger than that of a positive control, acarbose (IC50; 214.5 µM).
RESUMO
Blood transfusion is life-saving in massive hemorrhage. Before pre-transfusion tests with ABO and RhD typing results are available, O RhD negative packed red blood cell (PRBC) units are used without cross-matching in emergency. RhD negative girls and women of child-bearing age should always receive RhD negative blood transfusions to prevent RhD-alloimmunization because anti-D-related hemolytic disease of fetus and newborn (HDFN) can result in mild to severe anemia, and in a worst-case scenario death of an RhD positive fetus and/or newborn. However, "wrong blood to wrong patient" happens unintentionally. Here we report an emergency blood transfusion with one unit of RhD positive PRBCs to an RhD negative young woman when estimated blood loss was 2500 mL during delivery and surgical removal of retained placenta. Realizing the mistake, management with high dose anti-D immunoglobulin (Ig) was initiated to remove the RhD positive red blood cells (RBCs) from the patient's circulation. Such mitigation is recommended only for girls and women of child-bearing age. Follow-up was performed by flow cytometry until RhD positive RBCs were no longer detected. Ten months after the delivery, antibody screening was negative. However, we still do not know whether we managed to prevent RhD-alloimmunization.
RESUMO
This study presents a phytochemical analysis of the leaves of Paramignya trimera, revealing the isolation of a new apotirucallane-type protolimonoid, identified as 25-O-methyl-1,2-dihydroprotoxylocarpin D (1), along with two known compounds (2 and 3). The known compounds were identified as (20S,21R,23R)-21,23-epoxy-7α,24,25-trihydroxy-21-O-methyl-3-oxoapotirucalla-14-ene (2) and 7α,24,25-trihydroxy-3-oxoapotirucalla-14-en-21,23-olide (3). The three apotirucallane-type protolimonoids (1-3) did not exhibit cytotoxicity against MCF-7 cells at a concentration of 100 µM. Interestingly, when MCF-7 cells were treated with compound 1 at various concentrations, a notable stimulatory response was observed, leading to a significant increase in cell viability, up to 127%.
RESUMO
From the EtOAc-soluble extract of the rhizomes of Zingiber montanum (J.Koenig) Link ex A.Dietr., a novel diphenylbutenoid, montadinin A (1) and a previously unreported phenylbutenoid compound, 1-(3,4-dimethoxyphenyl)but-3-en-2-ol (7), in natural source were isolated. Additionally, seven known phenylbutenoids were also identified. The structures of all compounds were elucidated through NMR spectroscopic interpretation. Compounds cis-3-(3,4-dimethoxyphenyl)-4-[(E)-3,4-dimethoxystyryl]cyclohex-1-ene (2), cis-4-[(E)-3,4-dimethoxystyryl]-3-(2,4,5-trimethoxyphenyl)cyclohex-1-ene (3), trans-3-(3,4,-dimethoxyphenyl)-4-[(E)-2,4,5-trimethoxystyryl]cyclohex-1-ene (5), and cis-3-(3,4-dimethoxyphenyl)-4-[(Z)-2,4,5-trimethoxylstyryl]cyclohex-1-ene (6) showed weak cytotoxicity against HepG2 cells with IC50 values of 122.9, 127.3, 257.5, and 168.5 µM, respectively.
RESUMO
From the methanolic-soluble extract of the wood of Artocarpus heterophyllus, four new flavones, artocarmins A-D (1-4), and three new chalcones, artocarmitins A-C (5-7), have been isolated together with 13 known compounds. Their structures were determined on the basis of the spectroscopic data. Compounds 1-4, 6, 7, 9-16, and 20 displayed significant tyrosinase inhibitory activity. The most active compound, morachalcone A (12) (IC50, 0.013 µM), was 3000 times more active as a tyrosinase inhibitor than a positive control, kojic acid (IC50, 44.6 µM).
Assuntos
Artocarpus/química , Chalconas/isolamento & purificação , Chalconas/farmacologia , Monofenol Mono-Oxigenase/antagonistas & inibidores , Chalconas/química , Estrutura Molecular , Pironas/farmacologia , Madeira/químicaRESUMO
From the MeOH extract of the aerial part of Blumea balsamifera L., a new dihydroflavonol, (2R,3S)-(-)-4'-O-methyldihydroquercetin (1), together with seven known compounds has been isolated. Their structures were elucidated on the basis of spectroscopic data. Compounds 1-4 and 6-8 displayed significant xanthine oxidase inhibitory activity in a concentration-dependent manner, and compounds 1, 6 and 8 showed more potent inhibitory activity, with IC50 values ranging from 0.23 to 1.91 µM, than that of a positive control allopurinol (IC50 2.50 µM).
Assuntos
Asteraceae/química , Inibidores Enzimáticos/isolamento & purificação , Quercetina/análogos & derivados , Xantina Oxidase/antagonistas & inibidores , Fracionamento Químico , Relação Dose-Resposta a Droga , Inibidores Enzimáticos/química , Flavonoides/química , Flavonoides/isolamento & purificação , Concentração Inibidora 50 , Metanol , Estrutura Molecular , Componentes Aéreos da Planta/química , Extratos Vegetais/química , Quercetina/química , Quercetina/isolamento & purificação , Relação Estrutura-AtividadeRESUMO
An extract from the rhizomes of Cassumunar ginger (Zingiber purpureum Roscoe). was found to have significant α-glucosidase inhibitory activity with an IC50 value of 6.3 µg/mL. Two new phenylbutenoids, cassudimin A (1) and cassumunol N (2), and seven known compounds (3-9) were isolated. Their structures and relative configurations of two new compounds were elucidated based on spectra interpretation. Compounds 1-3, 6-9 showed more potent α-glucosidase inhibitory activity than a positive control, acarbose (IC50 = 168.0 µM). Dehydrozingerone (6) exhibited the most potent α-glucosidase inhibition with an IC50 value of 8.3 µM. Compounds 7 and 9 were found in Z. purpureum rhizomes for the first time.
RESUMO
A phytochemical investigation of the rhizomes of Curcuma zedoaria was carried out, leading to the isolation of a new diphenylheptanoid, zedoaroxane A (1), together with four known compounds (2-5). Their structures were elucidated based on NMR spectroscopic data. All isolated compounds possessed α-glucosidase inhibitory activity, with the IC50 values ranging from 35.2 to 89.0 µM, more potent than that of the positive control acarbose (IC50, 214.5 µM).
Assuntos
Curcuma , Sesquiterpenos , Curcuma/química , Extratos Vegetais/química , Rizoma/química , Sesquiterpenos/químicaRESUMO
Following bioactivity-guided isolation, four new stilbene-like derivatives, named Strebluses E-H, were isolated from the EtOAc-soluble fraction of the stems of Streblus ilicifolius (Moraceae). Their chemical structures were elucidated based on NMR spectroscopic data interpretation and optical rotation calculation. Streblus E possesses potent tyrosinase inhibitory activity with an IC50 value of 0.1 µM. Oxy-tyrosinase has two bound Cu2+ ions and a peroxide group in the binding site, which has a role in the catalytic oxidation. Thus, a docking study of Streblus E with oxy-tyrosinase was performed to analyze the ligand-protein interactions. With in silico modelling, the S value and the ligand-protein interactions suggested that Streblus E showed lower binding affinity for oxy-tyrosinase than that of Streblus C.