Modification of the Estrogenic Properties of Diphenols by the Incorporation of Ferrocene. Generation of Antiproliferative Effects in Vitro

Heparin and nitric oxide (NO) attenuate changes to the pulmonary vasculature caused by prolonged hypoxia. Heparin may increase NO; therefore, we hypothesized that heparin may attenuate hypoxia-induced pulmonary vascular remodeling via a NO-mediated mechanism. In vivo, rats were exposed to normoxia (N) or hypoxia (H; 10% O2) with or without heparin (1,200 U · kg−1 · day−1) and/or the NO synthase (NOS) inhibitor N ω-nitro-l-arginine methyl ester (l-NAME; 20 mg · kg−1 · day−1) for 3 days or 3 wk. Heparin attenuated increases in pulmonary arterial pressure, the percentage of muscular pulmonary vessels, and their medial thickness induced by 3 wk of H. Importantly, althoughl-NAME alone had no effect, it prevented these effects of heparin on vascular remodeling. In H lungs, heparin increased NOS activity and cGMP levels at 3 days and 3 wk and endothelial NOS protein expression at 3 days but not at 3 wk. In vitro, heparin (10 and 100 U · kg−1 · ml−1) increased cGMP levels after 10 min and 24 h in N and anoxic (0% O2) endothelial cell-smooth muscle cell (SMC) coculture. SMC proliferation, assessed by 5-bromo-2′-deoxyuridine incorporation during a 3-h incubation period, was decreased by heparin under N, but not anoxic, conditions. The antiproliferative effects of heparin were not altered byl-NAME. In conclusion, the in vivo results suggest that attenuation of hypoxia-induced pulmonary vascular remodeling by heparin is NO mediated. Heparin increases cGMP in vitro; however, the heparin-induced decrease in SMC proliferation in the coculture model appears to be NO independent.

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Effect of Roasting and Brewing on the Antioxidant and Antiproliferative Activities of Tartary Buckwheat

Foods ◽

10.3390/foods9091331 ◽

2020 ◽

Vol 9 (9) ◽

pp. 1331

Author(s):

Ji-yeon Ryu ◽

Yoonseong Choi ◽

Kun-Hwa Hong ◽

Yong Suk Chung ◽

Somi Kim Cho

Keyword(s):

Breast Cancer Cells ◽

Room Temperature ◽

Tartary Buckwheat ◽

Flavonoid Content ◽

Total Polyphenol ◽

Antiproliferative Effects ◽

Long Time ◽

Short Time ◽

Antiproliferative Activities

We evaluated the effect of the roasting and brewing conditions of Tartary buckwheat (TB), which is widely used in infusion teas, on its antioxidant and antiproliferative activities in vitro. TB was roasted at 210 °C for 10 min and brewed at a high temperature for a short time (HTST; 85–90 °C, 3 min) or at room temperature for a long time (RTLT; 25–30 °C, 24 h). Roasted TB (RTB) tea brewed at RTLT had the highest total polyphenol content (TPC) and total flavonoid content (TFC) among the four TB teas for different roasting and brewing conditions. Moreover, RTB brewed at RTLT showed the greatest 2,2-diphenyl-1-picrylhydrazyl-, 2,2’-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid)-, and alkyl-scavenging activities. The TB tea brewed at RTLT had higher Fe2+-chelating activity than that brewed at HTST, irrespective of roasting. Moreover, RTB tea brewed at RTLT inhibited the proliferation of human pancreatic and breast cancer cells. Overall, RTB-RTLT displayed the largest effect on antioxidant and antiproliferative effects. Finally, rutin was found to possess the most pronounced effect on the antioxidant and antiproliferative activities of the TB teas. These results indicate that the antioxidant and antiproliferative activities of RTB are enhanced by RTLT brewing.

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Novel Polycondensed Partly Saturated β-Carbolines Including Ferrocene Derivatives: Synthesis, DFT-Supported Structural Analysis, Mechanism of Some Diastereoselective Transformations and a Preliminary Study of their In Vitro Antiproliferative Effects

Molecules ◽

10.3390/molecules25071599 ◽

2020 ◽

Vol 25 (7) ◽

pp. 1599

Author(s):

Kinga Judit Fodor ◽

Dániel Hutai ◽

Tamás Jernei ◽

Angéla Takács ◽

Zsófia Szász ◽

...

Keyword(s):

Methyl Esters ◽

Diffraction Measurement ◽

Ferrocene Derivatives ◽

Substitution Pattern ◽

Relative Configuration ◽

Antiproliferative Effects ◽

Aryl Aldehydes ◽

Dft Modeling ◽

Nmr Methods

Use of a Pictet-Spengler reaction of tryptamine and l-tryptophan methyl ester and subsequent reduction of the nitro group followed by further cyclocondensation with aryl aldehydes and formyl–substituted carboxylic acids, including ferrocene-based components, furnished a series of diastereomeric 6-aryl-substituted 5,6,8,9,14,14b-hexahydroindolo[2′,3′:3,4]pyrido[1-c]-quinazolines and 5,5b,17,18-tetrahydroindolo[2′,3′:3,4]pyrido[1,2-c]isoindolo[2,1-a]quinazolin-11-(15bH)-ones with the elements of central-, planar and conformational chirality. The relative configuration and the conformations of the novel polycyclic indole derivatives were determined by 1H- and 13C-NMR methods supplemented by comparative DFT analysis of the possible diastereomers. The structure of one of the pentacyclic methyl esters with defined absolute configuration “S” was also confirmed by single crystal X-ray diffraction measurement. Accounting for the characteristic substituent-dependent diastereoselective formation of the products multistep mechanisms were proposed on the basis of the results of DFT modeling. Preliminary in vitro cytotoxic assays of the products revealed moderate-to-significant antiproliferative effects against PANC-1-, COLO-205-, A-2058 and EBC-1 cell lines that proved to be highly dependent on the stereostructure and on the substitution pattern of the pending aryl substituent.

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An Ethanolic Extract of Boehmeria caudata Aerial Parts Displays Anti-inflammatory and Anti-tumor Activities

Planta Medica International Open ◽

10.1055/a-1111-9907 ◽

2020 ◽

Vol 7 (01) ◽

pp. e17-e25 ◽

Cited By ~ 1

Author(s):

Paula Pereira de Paiva ◽

Fabiana Regina Nonato ◽

Ana Lúcia Tasca Gois Ruiz ◽

Ilza Maria de Oliveira Sousa ◽

Rafael Rosolen Teixeira Zafred ◽

...

Keyword(s):

Anticancer Agents ◽

Ethanolic Extract ◽

Experimental Models ◽

New Drugs ◽

Antiproliferative Effects ◽

Aerial Parts ◽

Anti Inflammatory ◽

Inflammatory Action ◽

Effective Source

AbstractThe tumor microenvironment presents several therapeutic targets, with inflammation being one of them. In search of new drugs, plants have shown to be an effective source of potent anti-inflammatory and anticancer agents. This study aimed to evaluate the antitumoral and inflammatory activities of Boehmeria caudata aerial parts extract. Bioguided in vitro antiproliferative screening showed that phenanthroquinolizidine obtained from the aerial B. caudata ethanolic extract had a straight relationship with activity. Moreover, the orally administered ethanolic extract reduced Ehrlich solid tumor growth and displayed an anti-inflammatory effect in both evaluated experimental models (carrageenan-induced paw edema and croton oil-induced ear edema). These results suggest that the antitumor activity of the ethanolic extract could be explained by antiproliferative effects associated with anti-inflammatory action.

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Microwave-Assisted Synthesis, Proton Dissociation Processes, and Anticancer Evaluation of Novel D-Ring-Fused Steroidal 5-Amino-1-Arylpyrazoles

Applied Sciences ◽

10.3390/app10010229 ◽

2019 ◽

Vol 10 (1) ◽

pp. 229

Author(s):

Gergő Mótyán ◽

Ádám Baji ◽

Małgorzata Anna Marć ◽

Mohana Krishna Gopisetty ◽

Dóra I. Adamecz ◽

...

Keyword(s):

Human Cancer ◽

Condensation Reaction ◽

Microwave Assisted Synthesis ◽

Antiproliferative Effects ◽

Human Cancer Cells ◽

Microwave Assisted ◽

Proton Dissociation ◽

Ic50 Values ◽

Spectrophotometric Titrations

Taking into account the pharmacological relevance of heterocycle-fused natural steroids, the objective of the current study was to develop a multistep reaction sequence for the efficient synthesis of novel D-ring-condensed 5-amino-1-arylpyrazoles from dehydroepiandrosterone (DHEA). A condensation reaction of 16-formyl-DHEA with hydroxylamine afforded the corresponding oxime, which was demonstrated to be stable in one of its cyclic isoxazoline forms due to possible ring-chain tautomerism. The subsequent base-induced dehydration to a diastereomeric β-ketonitrile, followed by microwave-assisted heterocyclization with different arylhydrazines led to the desired pyrazoles. The generally good yields of the products depended slightly on the electronic character of the substituent present on the aromatic ring of the reagent. The proton dissociation processes of the DHEA-derived heterocycles were investigated in aqueous solution by UV-visible spectrophotometric titrations to reveal their actual chemical forms at physiological pH. The determined pKa values attributed to the pyrazole NH+ moiety were low (1.8–4.0) and varied by the different substituents of the benzene ring. The antiproliferative effects of the structurally similar compounds were screened in vitro on human cancer cells (namely on HeLa, U2Os, MCF-7, PC-3, and A549), along with a noncancerous cell line (MRC-5). The IC50 values of the most active derivative were determined on all cell lines.

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NF-кB inhibition by DHMEQ: in vitro antiproliferative effects on pilocytic astrocytoma and concise review of the current literature

Child s Nervous System ◽

10.1007/s00381-020-04625-3 ◽

2020 ◽

Vol 36 (11) ◽

pp. 2675-2684

Author(s):

M. F. Candido ◽

G. C. Baldissera ◽

M. Medeiros ◽

K. Umezawa ◽

María Sol Brassesco

Keyword(s):

Current Literature ◽

Pilocytic Astrocytoma ◽

Antiproliferative Effects ◽

Concise Review

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In vivo efficacy and metabolism of the antimalarial cycleanine and improved in vitro antiplasmodial activity of novel semisynthetic analogues

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.01995-20 ◽

2020 ◽

Author(s):

Fidelia Ijeoma Uche ◽

Xiaozhen Guo ◽

Jude Okokon ◽

Imran Ullah ◽

Paul Horrocks ◽

...

Keyword(s):

Metabolic Pathways ◽

High Performance ◽

Antimalarial Activity ◽

Biological Activities ◽

Antiplasmodial Activity ◽

Survival Times ◽

Antiproliferative Effects ◽

Future Evaluation

Bisbenzylisoquinoline (BBIQ) alkaloids are a diverse group of natural products that demonstrate a range of biological activities. In this study, the in vitro antiplasmodial activity of three BBIQ alkaloids (cycleanine (1), isochondodendrine (2) and 2′-norcocsuline (3)) isolated from the Triclisia subcordata Oliv. medicinal plant traditionally used for the treatment of malaria in Nigeria are studied alongside two semi-synthetic analogues (4 and 5) of cycleanine. The antiproliferative effects against a chloroquine-resistant Plasmodium falciparum strain were determined using a SYBR Green 1 fluorescence assay. The in vivo antimalarial activity of cycleanine (1) is then investigated in suppressive, prophylactic and curative murine malaria models after infection with a chloroquine-sensitive Plasmodium berghei strain. BBIQ alkaloids (1–5) exerted in vitro antiplasmodial activities with IC50 at low micromolar concentrations with the two semi-synthetic cycleanine analogues showing an improved potency and selectivity than cycleanine. At oral doses of 25 and 50mg/kg body weight of infected mice, cycleanine suppressed the levels of parasitaemia, and increased mean survival times significantly compared to the control groups. The metabolites and metabolic pathways of cycleanine (1) were also studied using high performance liquid chromatography electrospray ionization tandem mass spectrometry. Twelve novel metabolites were detected in rats after intragastic administration of cycleanine. The metabolic pathways of cycleanine were demonstrated to involve hydroxylation, dehydrogenation, and demethylation. Overall, these in vitro and in vivo results provide a basis for the future evaluation of cycleanine and its analogues as leads for further development.

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Structure-based design, synthesis and in vitro antiproliferative effects studies of novel dual BRD4/HDAC inhibitors

Bioorganic & Medicinal Chemistry Letters ◽

10.1016/j.bmcl.2017.07.054 ◽

2017 ◽

Vol 27 (17) ◽

pp. 4051-4055 ◽

Cited By ~ 19

Author(s):

Mingfeng Shao ◽

Linhong He ◽

Li Zheng ◽

Lingxiao Huang ◽

Yuanyuan Zhou ◽

...

Keyword(s):

Hdac Inhibitors ◽

Design Synthesis ◽

Antiproliferative Effects

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Antiproliferative effects of some novel synthetic solanidine analogs on HL-60 human leukemia cells in vitro

Steroids ◽

10.1016/j.steroids.2010.10.006 ◽

2011 ◽

Vol 76 (1-2) ◽

pp. 156-162 ◽

Cited By ~ 26

Author(s):

Renáta Minorics ◽

Thomas Szekeres ◽

Georg Krupitza ◽

Philipp Saiko ◽

Benedikt Giessrigl ◽

...

Keyword(s):

Leukemia Cells ◽

Human Leukemia ◽

Antiproliferative Effects ◽

Human Leukemia Cells

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Time-Dependent Degradation of Polyphenols from Thermally-Processed Berries and Their In Vitro Antiproliferative Effects against Melanoma

Molecules ◽

10.3390/molecules23102534 ◽

2018 ◽

Vol 23 (10) ◽

pp. 2534 ◽

Cited By ~ 3

Author(s):

Zorița Diaconeasa

Keyword(s):

Bioactive Compounds ◽

Food Industry ◽

Storage Time ◽

Polyphenolic Compounds ◽

Published Data ◽

Antiproliferative Effects ◽

Phytochemical Composition ◽

Thermally Processed ◽

Hydroxybenzoic Acids

Polyphenols are natural occurring micronutrients that can protect plants from natural weathering and are also helpful to humans. These compounds are abundantly found in fruits or berries. Because of berry seasonal availability and also due to their rapid degradation, people have found multiple ways to preserve them. The most common options are freezing or making jams. Polyphenol stability, during processing is a continuous challenge for the food industry. There are also multiple published data providing that they are sensitive to light, pH or high temperature, vectors which are all present during jam preparation. In this context the aim of this study was to assess phytochemical composition and bioactive compounds degradation after jam preparation. We also monitored their degradation during storage time and their in vitro antiproliferative potential when tested on melanoma cells. The obtained results revealed that when processed and stored in time, the bioactive compounds from berries jams are degrading, but they still exert antioxidant and antiproliferative potential. Prior to LC-MS analysis, polyphenolic compounds were identified as: flavonoids (anthocyanins (ANT), flavonols (FLA)) and non-flavonoid (hydroxycinnamic acids (HCA) and hydroxybenzoic acids (HBA)). The most significant decrease was observed for HCA compared to other classes of compounds. This variation is expected due to differences in constituents and phenolic types among different analyzed berries.

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