Search results for "IC50"
showing 10 items of 129 documents
Late Breaking Abstract - CRAC channel inhibition by RP3128 triggers potent anti-inflammatory effects in COPD or asthmatic patient-derived primary cel…
2018
Introduction: Calcium release activated calcium channels inhibitors have a potent role in treatment of autoimmune disorders. RP3128 is a novel and potent inhibitor of Calcium Release Activated Calcium (CRAC) channel activity with demonstrated efficacy in several models of immune-inflammatory disorders. The objective of this study was to assess the effect of RP3128 and combinations in attenuating inflammatory responses associated with respiratory diseases. Methods: Inhibition of antigen-induced cytokine release in primary T-lymphocytes was estimated. Peripheral blood neutrophils or mononuclear cells were isolated from COPD or asthmatic patients, pre-incubated with RP3128 for 0.5 h, and stimu…
Recent advances in the development of cyclin-dependent kinase 7 inhibitors.
2019
Abstract Cyclin dependent kinase 7 (CDK7) plays a double role as it activates several other cyclin dependent kinases and participates to the initiation of transcription. This kinase is overexpressed in various types of tumors. Relatively few selective CDK7 inhibitors have been up to now disclosed. Most of these inhibitors belong to two chemical families: pyrazolopyrimidines and pyrazolotriazines on one side and pyrimidines on another side. They also differ by their molecular mechanism of action. Some are acting as competitive inhibitors and some others are covalent inhibitors. With these tools, the understanding of the potential therapeutic interest of CDK7 inhibitors in cancer is rapidly g…
Polyketides from the marine-derived fungus Aspergillus falconensis: In silico and in vitro cytotoxicity studies.
2020
Abstract Fermentation of the marine-derived fungus Aspergillus falconensis, isolated from sediment collected from the Red Sea, Egypt on solid rice medium containing 3.5% NaCl yielded a new dibenzoxepin derivative (1) and a new natural isocoumarin (2) along with six known compounds (3–8). Changes in the metabolic profile of the fungus were induced by replacing NaCl with 3.5% (NH4)2SO4 that resulted in the accumulation of three further known compounds (9–11), which were not detected when the fungus was cultivated in the presence of NaCl. The structures of the new compounds were elucidated by HRESIMS and 1D/2D NMR as well as by comparison with the literature. Molecular docking was conducted fo…
Interactions between T-2 toxin and its metabolites in HepG2 cells and in silico approach
2021
Abstract The T-2 toxin (T-2) is commonly metabolized to HT-2 toxin (HT-2), Neosolaniol (NEO), T2-triol and T2-tetraol and they can modify the toxicity of T-2. In this study, T-2 and its modified forms were evaluated by in vitro and in silico methods. The in vitro cytotoxicity individually was evaluated by MTT and Total Protein Content (PC) assays in human hepatocarcinoma (HepG2) cells. The order of IC50 was T-2 tetraol > T-2 triol > NEO > T-2 = HT-2. The T-2 and HT-2 evidenced the highest cytotoxic effect in HepG2 cells individually. No differences were observed in binary combinations tested and the two mycotoxins in the mixture tested individually. The T-2+HT-2 combination showed the highe…
Cyclic heptapeptides from the soil-derived fungus Clonostachys rosea
2019
Abstract Three new cyclic heptapeptides (1–3) together with three known compounds (4–6) were isolated from a solid rice culture of the soil-derived fungus Clonostachys rosea. Fermentation of the fungus on white beans instead of rice afforded a new γ-lactam (7) and a known γ-lactone (8) that were not detected in the former extracts. The structures of the new compounds were elucidated on the basis of 1D and 2D NMR spectra as well as by HRESIMS data. Compounds 1 and 4 exhibited significant cytotoxicity against the L5178Y mouse lymphoma cell line with IC50 values of 4.1 and 0.1 µM, respectively. Compound 4 also displayed cytotoxicity against the A2780 human ovarian cancer cell line with an IC50…
Essential oil of Citrus lumia Risso: Phytochemical profile, antioxidant properties and activity on the central nervous system
2018
Citrus lumia Risso Essential oil Antioxidant properties Anti-cholinesterase activity Cytotoxicity Neuroactive effects 1. Introduction Plants that produce essential oils (EOs) represent a large part of natural flora and an important resource in various fields such as pharmaceutical, food and cosmetic industries, due to their flavor, fra- grance and biological activity (Swamy et al., 2016). EOs play a pivotal role in the growth and colonization of plants, giving color and scent to reproductive organs, attracting pollinators, favoring seed dispersion (Sharifi-Rad et al., 2017), and defending the plant against abiotic (light, temperature, etc.) and biotics (herbivores, harmful insects and pa- t…
Phenylsulphonyl urenyl chalcone derivatives as dual inhibitors of cyclo-oxygenase-2 and 5-lipoxygenase
2005
Two series of phenylsulphonyl urenyl chalcone derivatives (UCH) with various patterns of substitution were tested for their effects on nitric oxide (NO) and prostaglandin E2 (PGE2) overproduction in RAW 264.7 macrophages. None of the tested compounds reduced NO production more than 50% at 10 microM but most of them inhibited the generation of PGE2 with IC50 values under the micromolar range. Me-UCH 1, Me-UCH 5, Me-UCH 9, Cl-UCH 1, and Cl-UCH 9 were selected to evaluate their influence on human leukocyte functions and eicosanoids generation. These derivatives selectively inhibited cyclo-oxygenase-2 (COX-2) activity in human monocytes being Me-UCH 5 the most potent (IC50 0.06 microM). Selecte…
Interaction effects of enniatin B, deoxinivalenol and alternariol in Caco-2 cells.
2015
Enniatin B (ENN B), deoxinivalenol (DON) and alternariol (AOH) are secondary metabolites of filamentous fungi. These mycotoxins are contaminants of vegetables and cereals. They are cytotoxic and their effects are enhanced by their mixtures. The objectives of this study were to compare the cytotoxicity of ENN B, DON and AOH alone or in combination in human adenocarcinoma (Caco-2) cells and to evaluate the type of interactions of mycotoxin mixtures by the isobologram analysis. Cells were treated with concentrations ranging from 1.85 to 90μM (AOH) and from 0.312 to 10μM (for ENN B and DON), individually and in combination of two and three mycotoxins (from 1.85 to 30μM for AOH and from 0.312 to…
Efficient Production of Isoflavonoids by Astragalus membranaceus Hairy Root Cultures and Evaluation of Antioxidant Activities of Extracts
2014
In this study, Astragalus membranaceus hairy root cultures (AMHRCs) were established as an attractive alternative source for the efficient production of isoflavonoids (IF). A. membranaceus hairy root line II was screened as the most efficient line and was confirmed by PCR amplification of rolB, rolC and aux1 genes. Culture parameters of AMHRCs were systematically optimized, and five main IF constituents were quali-quantitatively determined by LC-MS/MS. Under optimal conditions, the total IF accumulation of 34 day old AMHRCs was 234.77 μg/g dry weight (DW). This yield was significantly higher compared to that of 3 year old field grown roots (187.38 μg/g DW). Additionally, in vitro antioxidan…
Inhibition of Efavirenz Metabolism by Sertraline and Nortriptyline and Their Effect on Efavirenz Plasma Concentrations.
2015
ABSTRACT Between 22 and 45% of HIV-positive subjects are likely to report symptoms of depression. Considering this background, a potential pharmacokinetic interaction between the nonnucleoside reverse transcriptase inhibitor efavirenz (EFV) and two antidepressants, sertraline (SRT) and nortriptyline (NT), was studied. Rats were administered EFV alone or together with the antidepressants, and changes in the plasma levels and pharmacokinetic parameters of EFV were analyzed. Additional in vitro experiments with rat and human hepatic microsomes were carried out to evaluate the inhibitory effect of SRT and NT on EFV metabolism by determining the formation rate of the major EFV metabolite (8-OH-E…