Search results for "DISCOVERY"
showing 10 items of 4119 documents
Recent advances in computational design of potent aromatase inhibitors: open-eye on endocrine-resistant breast cancers.
2019
Introduction: The vast majority of breast cancers (BC) are estrogen receptor positive (ER+). The most effective treatments to fight this BC type rely on estrogen deprivation therapy, by inhibiting the aromatase enzyme, which performs estrogen biosynthesis, or on blocking the estrogens signaling path via modulating/degrading the estrogen's specific nuclear receptor (estrogen receptor-?, ER?). While being effective at early disease stage, patients treated with aromatase inhibitors (AIs) may acquire resistance and often relapse after prolonged therapies. Areas covered: In this compendium, after an overview of the historical development of the AIs currently in clinical use, and of the computati…
Toward a Rational Design of Polyamine-Based Zinc-Chelating Agents for Cancer Therapies.
2020
In vitro viability assays against a representative panel of human cancer cell lines revealed that polyamines L1a and L5a displayed remarkable activity with IC50 values in the micromolar range. Preliminary research indicated that both compounds promoted G1 cell cycle arrest followed by cellular senescence and apoptosis. The induction of apoptotic cell death involved loss of mitochondrial outer membrane permeability and activation of caspases 3/7. Interestingly, L1a and L5a failed to activate cellular DNA damage response. The high intracellular zinc-chelating capacity of both compounds, deduced from the metal-specific Zinquin assay and ZnL2+ stability constant values in solution, strongly sup…
Identification of Biphenyl-Based Hybrid Molecules Able To Decrease the Intracellular Level of Bcl-2 Protein in Bcl-2 Overexpressing Leukemia Cells
2009
With the aim of enhancing the structural complexity and diversity of an existing collection of bi- and terphenyl compounds, we synthesized hybrid molecules comprising of spirocyclic ketones (a complexity-bearing core) and bi/terphenyls (privileged fragments). Compounds 1, 3, 4, and 6 showed well-defined activity on apoptosis and differentiation, making them potential leads for development as new anticancer agents and chemical probes to study signaling networks in neoplastic cells.
Antimicrobial and antiproliferative activity of Peucedanum nebrodense (Guss.) Strohl.
2003
Abstract Acetone extract of Peucedanum nebrodense (Guss.) Strohl., a rare endemic species from the Madonie mountains (Sicily), was tested in vitro for its antimicrobial activity against bacterial reference strains and antiproliferative activity against K562 (human chronic myelogenous leukemia), HL-60 (human leukemia) and L1210 (murine leukemia) cell lines. The acetone extract showed antiproliferative IC 50 values in the range of 14–0.27 μg/ml.
Farmed Gilthead Sea Bream (Sparus aurata) by-Products Valorization: Viscera Oil ω-3 Enrichment by Short-Path Distillation and In Vitro Bioactivity Ev…
2021
This study shows a pilot scale protocol aimed to obtain an omega 3-enriched oil after the processing of farmed gilthead sea bream viscera (SBV)
Effects of Ultrasound-Assisted Extraction and Solvent on the Phenolic Profile, Bacterial Growth, and Anti-Inflammatory/Antioxidant Activities of Medi…
2020
© 2020 by the authors.
Antioxidant Pathways in Alzheimers Disease: Possibilities of Intervention
2011
Alzheimer's disease (AD) is closely related to the occurrence of oxidative stress. It was claimed that all pathophysiological mechanisms involved in the onset and progression of AD are related to oxidative stress. Thus, it is important to evaluate if there is oxidative stress as well as the mechanism by which this happens in AD patients as well as in animal models of AD. Extracellular plaques of amyloid b peptides (Aβ), a hallmark of the disease, have been postulated to be more protective than damaging in terms of oxidative stress because they may be chemical sinks in which heavy metals are placed. More than a decade ago we reasoned that damage due to Ab might be caused not by extracellular…
Dietary polyphenols in chemoprevention and synergistic effect in cancer: Clinical evidences and molecular mechanisms of action
2020
Abstract Background Epidemiological studies has revealed that a diet rich in fruits and vegetables could lower the risk of certain cancers. In this setting, natural polyphenols are potent anticancer bioactive compounds to overcome the non-target specificity, undesirable cytotoxicity and high cost of treatment cancer chemotherapy. Purpose The review focuses on diverse classifications of the chemical diversity of dietary polyphenol and their molecular targets, modes of action, as well as preclinical and clinical applications in cancer prevention. Results The dietary polyphenols exhibit chemo-preventive activity through modulation of apoptosis, autophagy, cell cycle progression, inflammation, …
Tiliroside and gnaphaliin inhibit human low density lipoprotein oxidation.
2004
Two flavonoids, gnaphaliin and tiliroside, isolated from Helichrysum italicum, were studied in vitro for their capacity to inhibit Cu(2+)-induced human low density lipoprotein (LDL) and diluted plasma oxidation. LDL oxidation was monitored by conjugated diene, thiobarbituric acid-reactive substances (TBARS) formation and electrophoretic mobility on agarose gel. Gnaphaliin and tiliroside increased the lag-phase for diene conjugate production in a dose-dependent manner. The reduction of TBARS production confirmed the antioxidant activity of gnaphaliin and tiliroside with 50% inhibitory concentration (IC(50)) values of 8.0+/-3.9 microM and 7.0+/-2.6 microM respectively. Furthermore, the flavon…
Preparation of C-23 esterified silybin derivatives and evaluation of their lipid peroxidation inhibitory and DNA protective properties.
2009
A diverse series of C-23 esterified silybin derivatives (1a-n) were designed and synthesized. The antioxidative properties of these compounds were evaluated by 1,1-diphenyl-2-picrylhydrazyl (DPPH) and superoxide anion radical scavenging, ferrous ion chelation, and inhibition of rat liver homogenate lipid peroxidation. Their protective effects on the prevention of hydrogen peroxide induced DNA damage were also investigated. Most of the synthesized compounds exhibited more effective antioxidant activities than silybin. The esterified silybin analogues displayed satisfactory performance especially on iron chelation and antiperoxidative activity. Compound 1n in particular exhibited remarkable a…