Anti-tumor Properties of Stilbene-based Resveratrol Analogues: Recent Results:

Recent literature about stilbene-based analogues of resveratrol (1) has been reviewed, and a total of 94 compounds are reported (see structures 4 – 97), selected either for their promising anti-tumor properties or as comparative terms in SAR studies. As a general outline, these recent literature data confirm the previously reported observation that minimal modification in the nature and position of the substituents on the stilbene nucleus may cause large variations in their biological activity and, more specifically, in their anti-tumor properties. Among the polyhydroxylated stilbenes, it has been established that those with either a catechol or pyrogallol moiety are far better radical scavengers than either 1 or other analogues lacking an ortho-dihydroxy group, and this property was shown to be related to pro-apoptotic activity. In the large majority of cases where couples of E- and Z-isomers were evaluated for either cytotoxic or pro-apoptotic activity, the Z-isomers were significantly more active than their E analogues; nevertheless, a general rule stating that stilbenoids with Z configuration of the double bond display a considerably higher antiproliferative activity than their E-isomers cannot be considered as established. A variety of methoxystilbenes has been reported recently: in many cases these analogues showed either potent antiproliferative and pro-apoptotic activity or strong inhibition of TNFα-induced activation of NF- kB. Globally considered, polymethoxystilbenes are a sub-group of great interest among the resveratrol analogues: these analogues appear worthy of a deeper evaluation also in connection with their potential anti-angiogenic properties. In addition, in vivo studies indicate that methoxystilbenes undergo different metabolic conversion and have a higher bioavailability than resveratrol. The potent activity of some amino- and halogenated stilbenes is undoubtedly worthy of attention, but the toxicity of these compounds to normal cells has rarely been evaluated. In conclusion, the synthesis and evaluation of stilbene-based resveratrol analogues proved to be a highly active field of research and has recently afforded compounds with either cytotoxic or pro-apoptotic activity in the nanomolar range. Nevertheless, the exact structural determinants to optimize the anti-tumor properties of these compounds and details of their mechanism of action remain to be clarified

Individual and contextual determinants of inter-regional mobility in cancer patients

This paper will present an investigation of inter-regional mobility in patients with a diagnosis of cancer. By virtue of the availability of geocoded information relating to a patient's place of residence, the effect of socio-economic status and other individual characteristics regarding inter-regional mobility will be analysed by means of multilevel logit models. The results demonstrate the influence of age and comorbidity on mobility propensity, in addition to the treatment type, which plays a role in patient mobility. As contextual determinants, patients residing in less deprived areas show greater mobility than those who reside in materially deprived areas. The extent of patient mobility, and its dependence on their socio-economic status raises issues of equity, as well as regional policy considerations

Chemoenzymatic Synthesis and Some Biological Properties of O-phosphoryl Derivatives of (E)-resveratrol

3- O-, 3,5-di- O- and 4′- O-phosphoryl derivatives of ( E)-resveratrol have been obtained following a chemoenzymatic strategy. Variedly acylated resveratrol derivatives have been obtained first by exploiting regioselective properties of Pseudomonas cepacea or Candida antarctica lipases in organic solvents. Each acyl-resveratrol was then phosphorylated by the phosphoramidite chemistry protocol and in sequence freed of protective groups, affording the desired O-phosphoryl derivative. Following UV-absorption spectroscopic investigation on the interaction of the newly synthesized compounds with DNA, 4′- O-phosphorylresveratrol exhibited the best binding affinity. As a result of cytotoxicity tests, 3- O-phosphorylresveratrol was more active than resveratrol against DU 145 prostate cancer cells

Antiproliferative Activity of Methylated Analogues of E- and Z-Resveratrol

Abstract The stilbenoids E-resveratrol (E-3,5,4′-trihydroxystilbene, 1), E-3,5,4′-trimethoxystilbene (2), E-3,4,4′-trimethoxystilbene (3) and E-3,4′-dimethoxy-5-hydroxystilbene (4) were converted by photoisomerization to their corresponding Z-isomers 5D8. Compounds 1D8 were subjected to antiproliferative activity bioassays towards a set of four different human cancer cell lines, namely DU-145 (androgen not responsive human prostate tumor), LNCaP (androgen responsive human prostate tumor), M-14 (human melanoma) and KB (human mouth epidermoid carcinoma). The methylated analogues of 1 are more active than the natural lead in the majority of bioassays. The most active compound was Z-3,5,4′-trimethoxystilbene (6), which showed against DU-145 and LNCaP cells GI50 values close to those of the anticancer drug vinorelbine; 6 resulted more active than its E-isomer 2 towards DU-145, LNCaP and especially KB cell lines. A number of methylated Z-isomers displayed a higher activity than their E-isomers, but E-resveratrol (1) was more active than Z-resveratrol (5) towards all the tested cell lines

Bioassay-guided isolation of antiproliferative compounds from grape (Vitis vinifera) stems.

The fractionation, guided by cell-growth inhibition assay, of the EtOAc crude extract from grape stems of the Sicilian Vitis vinifera variety 'Nerello Mascalese' allowed identification of ten constituents, isolated either as pure compounds (1, 3–5, 7–10) or inseparable mixtures (2a-d and 6a-e). The pure constituents were: two triterpenoid acids, oleanolic (1) and betulinic acids (5); daucosterol (7); a stilbenoid, E-resveratrol (3) and its dimer E-ε-viniferin (4); the simple phenol gallic acid (8); and the flavanols catechin (9) and gallocatechin (10). Four 6′- O-acyldaucosterols (2a-d) and five 1,2-di- O-acyl-3- O-β-D-galactopyranosyl glycerols (6a-e) were also identified as inseparable mixtures. All the isolated compounds were subjected to spectroscopic analysis and MTT bioassay on MCF-7 human breast cancer cells. The majority showed growth-inhibitory activity, 5 being the most active (GI50 = 0.57 μM). Compounds 3–5 were also tested on HT-29, U-87-MG and U-373-MG cell lines

Large area SiC-UV phothodiode for spectroscopy portable system

In this work, we present the extensive characterization of large area Silicon Carbide based UV sensors candidate for outdoors spectroscopic applications of gas or liquid. The proposed SiC Schottky devices exhibit dark current density of 0.12 nA/cm2 @ 15 V, a 0.12 A/W responsivity @ 300 nm, optimal visible blindness and switching time of ~ 190 ns. Effects of temperature on the sensor performance, of crucial interest for outdoors applications, are also examined in the range from -20 °C to 90 °C.Published2931 - 29367TM. Sviluppo e Trasferimento TecnologicoJCR Journa

Moringa oleifera Protects SH-SY5YCells from DEHP-Induced Endoplasmic Reticulum Stress and Apoptosis

Moringa oleifera (MO) is a medicinal plant that has been shown to possess antioxidant, anticarcinogenic and antibiotic activities. In a rat model, MO extract (MOe) has been shown to have a protective effect against brain damage and memory decline. As an extending study, here, we have examined the protective effect of MOe against oxidative stress and apoptosis caused in human neuroblastome (SH-SY5Y) cells by di-(2-ethylhexyl) phthalate (DEHP), a plasticizer known to induce neurotoxicity. Our data show that MOe prevents oxidative damage by lowering reactive oxygen species (ROS) formation, restoring mitochondrial respiratory chain complex activities, and, in addition, by modulating the expression of vitagenes, i.e., antioxidant proteins Nrf2 and HO-1. Moreover, MOe prevented neuronal damage by partly inhibiting endoplasmic reticulum (ER) stress response, as indicated by decreased expression of CCAAT-enhancer-binding protein homologous protein (CHOP) and Glucose-regulated protein 78 (GRP78) proteins. MOe also protected SH-SY5Y cells from DEHP-induced apoptosis, preserving mitochondrial membrane permeability and caspase-3 activation. Our findings provide insight into understanding of molecular mechanisms involved in neuroprotective effects by MOe against DEHP damag

Hydrogen Sulfide and Carnosine: Modulation of Oxidative Stress and Inflammation in Kidney and Brain Axis

Emerging evidence indicates that the dysregulation of cellular redox homeostasis and chronic inflammatory processes are implicated in the pathogenesis of kidney and brain disorders. In this light, endogenous dipeptide carnosine (β-alanyl-L-histidine) and hydrogen sulfide (H2S) exert cytoprotective actions through the modulation of redox-dependent resilience pathways during oxidative stress and inflammation. Several recent studies have elucidated a functional crosstalk occurring between kidney and the brain. The pathophysiological link of this crosstalk is represented by oxidative stress and inflammatory processes which contribute to the high prevalence of neuropsychiatric disorders, cognitive impairment, and dementia during the natural history of chronic kidney disease. Herein, we provide an overview of the main pathophysiological mechanisms related to high levels of pro-inflammatory cytokines, including interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and neurotoxins, which play a critical role in the kidney–brain crosstalk. The present paper also explores the respective role of H2S and carnosine in the modulation of oxidative stress and inflammation in the kidney–brain axis. It suggests that these activities are likely mediated, at least in part, via hormetic processes, involving Nrf2 (Nuclear factor-like 2), Hsp 70 (heat shock protein 70), SIRT-1 (Sirtuin-1), Trx (Thioredoxin), and the glutathione system. Metabolic interactions at the kidney and brain axis level operate in controlling and reducing oxidant-induced inflammatory damage and therefore, can be a promising potential therapeutic target to reduce the severity of renal and brain injuries in humans

protective effect of a new hyaluronic acid carnosine conjugate on the modulation of the inflammatory response in mice subjected to collagen induced arthritis

Abstract Several studies demonstrated the pharmacological actions of carnosine as well as hyaluronic acid (HA) during joint inflammation. In that regard, the aim of this study was to investigate the protective effect of a new HA -Carnosine conjugate (FidHycarn) on the modulation of the inflammatory response in mice subjected to collagen-induced arthritis (CIA). CIA was induced by two intradermal injections of 100 μl of an emulsion of collagen (CII) and complete Freund's adjuvant (CFA) at the base of the tail on day 0 and 21. At 35 day post CIA induction, the animals were sacrificed. CII injection caused erythema and edema in the hind paws, histological alterations with erosion of the joint cartilage as well as behavioral changes. Oral treatment with FidHycarn starting at the onset of arthritis (day 25) ameliorated the clinical signs, improved behavioral deficits as well as decreased histological and radiographic alterations. The degree of oxidative damage evaluated by inducible nitric oxide synthase (iNOS), nitrotyrosine, poly-ADP-ribose (PAR) expressions and malondialdehyde (MDA) levels, was also significantly reduced in Carnosine+HA association and FidHycarn treated mice. Moreover, the levels of proinflammatory cytokines and chemokines and cyclo-oxygenase COX-2 enzyme were also more significantly reduced by Carnosine+HA and FidHycarn compared to carnosine alone. However, interestingly, in some cases, the effects of FidHycarn were more important than Carnosine+HA association and not statistically different to methotrexate (MTX) used as positive control. Thus, the conjugation of Carnosine with HA (FidHycarn) could represent an interesting therapeutic strategy to combat arthritis disorders