142 research outputs found
Inibitori delle topoisomerasi: derivati chinolin-chinonici con attività antiproliferativa
No full textMicrowave Assisted Synthesis of Pyridophenoxazinones, a class of Powerful Antiproliferative Compounds
No full textChemotherapy is the most common treatment of cancer that consists of the use of antineoplastic drugs to destroy cancerous cells. Traditional drugs used in chemotherapy act especially on the cell duplication processes. They are non-specific and cause many undesired concurrent effects on the healthy cells. For this reason, during the last decade, the oncological research has focused on the multimodal therapy, a combination of anticancer treatments acting simultaneously on different biological domains, able to inhibit proliferation of tumor cells present in different phases of the cell cycle(1). In order to obtain new antiproliferative compounds good for acting through the forementioned mechanisms, including DNA intercalation and topoisomerase inhibition, our attention was focused on the derivatives of pyridophenoxazinone (PPH, 1 R=H) system, an iminoquinone containing a planar tetracyclic system suitable for intercalating DNA G-C base pairs in a site specific mode(2).
Namely, we designed, after molecular modeling calculations, PPH carboxyamide derivatives holding at C-9 and C-10 positions an amino acidic chain or a sugar.
Unfortunately, the real obstacle to the availability of such molecule was represented by their synthesis. Therefore, in our opinion it seems to be worthwhile to report a new microwave (μW) assisted synthetic procedure to prepare PPH carboxyamides. In order to assess the validity of our method, we applied the procedure to the synthesis of variously substituted PPHs 1 and received evidence that microwave irradiation enables the preparation of those compounds in high yields and short reaction times
New approach in the treatment of inflammation: development of 5-LOX/sEH dual inhibitors and their pharmacological characterization (NAIDI)- PRN2022 PNNR
No full textDespite anti-inflammatory drug discovery is very intensive, inflammatory diseases remain among the most serious health burdens
and the medical need for more potent and safe anti-inflammatory drugs still remains. Moreover, despite the number of druggable
inflammatory targets constantly grows, especially in the most severe disorders, innovative agents usually fail to attain therapeutic
efficacy. This is probably due to the wide use of the one target–one drug approach that proven not to be a reliable approach in this
context. In fact, inflammation is a very complex pathophysiological process, involving a myriad of enzymes, mediators, and
receptors, producing proinflammatory agents as well as resolvins. Therefore, pharmacological modulation of a single target tends to
generate shunting phenomena that can compromise therapeutic efficacy. This is why, robust anti-inflammatory therapies often
involve the use of multiple drugs, but considering the drawbacks of polypharmacy, a multitarget polypharmacological approach
appears to be more suitable. On the other hand, polypharmacology usually relies on serendipity discovery and aprioristic knowledge
of the involved targets. This is an inherent limit to the rational design of truly innovative multitarget molecules and the reason why
the polypharmacology approach in drug design should be supported by cutting-edge technologies to highlight all the different
pathways responsible for the multitarget drug effect in a complex biological system. Therefore, polypharmacology needs in-depth
analyses of complex pathological pathways using disruptive omics technologies. In particular, metabolomics recently revealed its
dramatic potential in this context. Researchers from the research consortium responsible for the present project have recently
identified an indoline-based compound as dual 5-lipoxygenase (5-LOX) and soluble epoxide hydrolase (sEH) inhibitor. The molecule
showed good efficacy when challenged in vitro, also showing remarkable in vivo effects, despite its poor pharmacokinetic properties
(Compound 73, Figure 1). Therefore, this molecule represents an interesting hit compound for a hit-to-led development medicinal
chemistry campaign aimed to the preclinical development of dual 5-LOX/sEH inhibitor as anti-inflammatory agents. The project will
be based on three different tasks: 1) rational design and synthesis of compound new analogues of compound 73 to be screened for
their enzymatic inhibitory efficacy and their in vitro pharmacokinetic properties; 2) In vivo testing of selected compounds in mouse
model of pancreatitis and peritonitis along with the in vivo pharmacokinetic assessments; 3) metabolomic analyses on biofluids,
tissues and cells to shed light about the modulated molecular targets
Synthesis and antiviral activity of quinolone and oxazine derivatives
No full textA new class of synthetic quinonic compounds acting as antiproliferative agents”,. A. Bolognese, T. Di Meo, M. Manfra, G. Correale, O. Mazzoni, E. Novellino, G. Brunetti, L. Sanna, D. Del piano, P. La Colla
Abstract of XVIth International Symposium on Medicinal Chemistry
BOLOGNA
18-22 SETTEMBRE 200
POLYPHENOLIC PROFILE IN BERRY SKIN AND WINE OF VITIS VINIFERA L. CV. AGLIANICO (BASILICATA, ITALY)
No full textAnthocyanins are a very large group of red-blue polyphenol plant pigments, located within vacuoles of the skin cells of red grapes and characterized by a positive charge on the molecule which enables them to absorb light. These naturally occurring pigments from grapes are glycosides having a sugar bonded at the 3 position. The presence of this sugar helps the anthocyanins maintain solubility in water and allows pigments to diffuse into the must and wine during maceration, contributing to the color and antioxidant properties of red wines. The antioxidant properties, named as total antioxidant capacity (TAC) are well known and are correlated with electron transfer processes promoted by glycosilated and methoxy derivates anthocyanins as malvidin-3-glucoside arising from the free anthocyanin fraction of the red wines. Based on the widely accepted knowledge that antioxidants are potent scavengers of free radicals and serve as inhibitors at both initiation and promotion-propagation stages of tumor promotion-carcinogenesis and protect cells against oxidative damage, it seemed of interest to investigate anthocyanin presence and composition within the grape berries of Aglianico (Basilicata-Italy) [1], one of the most ancient vineyards introduced from Greece in the southern Italy in pre-Roman times.
References:
[1] Manfra, M.; DeNisco, M.; Bolognese, A.; Nuzzo, V.; Sofo, A; Scopa, A.; Santi, L.; Tenore, G.C.and E.Novellino.2011. Anthocyanin composition and extractability in berry skin and wine of Vitisvinifera L. cv. Aglianico.J. Sci. FoodAgric. 91:2749-275
Ishtar Phytotherapeutic Products (Start Cup Campania 2010)
No full textIl progetto risponde alla crescente domanda che sale da tutto il mondo occidentale di ritrovare nella fitoterapia quei rimedi che si sono accreditati nel tempo della storia umana;
praticare l’automedicazione usando rimedi più soft dei comuni farmaci.
La mission di ISHTAR consiste nell’uso della “FORZA ROSSA”, cioè nell’uso dei pigmenti e principi attivi presenti in frutta e ortaggi rossi (antocianine, resveratrolo, acido ellagico e licopene) che hanno la proprietà di combattere e prevenire obesità, sindrome metabolica e diabete, tre diffuse patologie tipiche dei nostri tempi.
Queste sostanze, che hanno effetti positivi sul tessuto grasso, sui muscoli scheletrici e sul tessuto epatico, provocano l’abbassamento del livello di glucosio nel sangue, l’aumento del metabolismo ossidativo dei grassi e in definitiva un effetto dimagrante ed antidiabetico
Microwave-Assisted Synthesis of Pyridophenoxazinones, a Class of Antiproliferative Compounds
No full textMicrowave (MW) irradiation allows to prepare a mini-library of pyridophenoxazinone derivatives, that are crucial intermediates in the synthesis of new antiproliferative compounds, active for human lymphoma/leukemia. The optimized procedure, consisting of a continuous input power of 50 W (808C) and a reaction time of 30 min, leads in very satisfactory yields to both regioisomers 5H-pyrido[2,3a]phenoxazin-5-ones and isomeric 5H-pyrido[3,2-a]phenoxazin 5-ones, starting from readily available quinoline-5,8-dione and substituted 2-aminophenols (APhOHs). Broad functional group tolerance was observed. The
availability of derivatives carrying a carboxyl group at the C-9 and C-10 positions enables the synthesis of a new family of 5Hpyridophenoxazin-5-one conjugates that were shown to exhibit good anti-cancer activity
Synthesis, Antiproliferative Activity, and Molecular Modelling of New DNA Intercalating Pyridophenoxazinone Carboxamides
No full textClinical studies have shown that multimodal therapy, a combination of anticancer treatments
acting simultaneously on different biological targets is able to inhibit the proliferation of tumor cells
present in different phases of the cell cycle. This new therapeutic approach improves the patient's
survival and decreases the drug resistance.1
To obtain new antiproliferative compounds able to act
through multimodal mechanisms on the cancerous cells, including DNA intercalation and
topoisomerase inhibition,2
derivatives of pyridophenoxazinone carboxylic acids the carboxamides
1a-d and 2a-d, holding at C-9 and C-10 positions an aminoacidic chain, were designed by
molecular modelling calculation, synthesized and evaluated for their inhibitory effect on a panel of
solid and liquid tumor cell lines and found active at submicromolar concentration. Compound 2a
was the most active, particularly on solid tumor
Different water and light regimes affect ionome composition in grapevine (Vitis vinifera L.)
No full textMany inorganic cations play a major role in winemaking
processes and wine quality. For this reason, chemistry at the elemental level ("ionomic") of the grape berry is of concern not only to the viticulturist, but also to the oenologist due to their direct impact on juice and must composition, which in turn affect wine quality. The aim of this research was to evaluate the effect
of reduced irrigation and incident light (by means
of micronized calcite) on the berry skin ionome of the
Italian red grape 'Aglianico'. The study was carried out
in a five-years-old vineyard (Vitis vinifera L. 'Aglianico')
located in Southern Italy. Half of the plants (IRR) were drip irrigated, whereas the other half were not irrigated (NIR). Half of IRR and NIR plants were treated with Megagreen® micronized calcite. In all the treatments, plant water status and gas exchange were determined. The mean values of stem water potential (ψw) during the experiment were –1.02 and –1.10 MPa in IRR and NIR, respectively. The calcite treatments did not show changes in ψw values if compared to the untreated ones. The values of gas exchange were not statistically different among the four treatments. Grape berries were separated into three groups of mass, and the levels of macroelements, microelements and lanthanides were
measured. Irrigation and calcite significantly affected
macroelements distribution in all the three groups of
mass, with Fe, Cu and Zn being significantly higher in
the IRR and calcite-treated treatments. The effect of irrigation on the changes in microelement levels was significant for some elements. Calcite-treated vines showed higher mean values of Co, Cd, Hg and Pb. Regarding lanthanides, in calcite-untreated vines, irrigation determined significant decreases in average La, Ce, Nd, whereas in calcite-treated vines, increases in the mean concentrations of Ce, Nd, Sm, Gd, Dy, Er and Yb were found. Generally, lanthanide levels did not change between calcite-treated and untreated vines, and in all the treatments Lu resulted to be the most abundant one. Macroelements, microelements and lanthanide levels generally decreased with decreasing berry weight. The dynamics of the extractability of metals from grape berries to must during fermentation could be used to predict wine quality during the following processes and for wine traceability purposes
New Seleno-Glyconjugates for Nutraceutical Application
No full textOxidative stress is a disequilibrium redox condition that occurs due to high concentration of prooxidant
reactive species (RS) and, by comparison, a lower concentration of endogenous
antioxidants in the body.1 Oxidative stress, caused by RS, is involved into the genesis of different
pathologies such as inflammatory bowel disease, cardiovascular disease, Alzheimer’s disease,
diabetes and cancer.2 Nutraceuticals could be used to prevent oxidative stress as an additional health
benefit along with nutrition.1 The use of exogenous antioxidants can ameliorate this stressful
condition and restore the redox disequilibrium.3 Polyphenols have a potential health-promoting
effect, however, show a low bioavailability.4 For this reason, synthesis of organic seleniumcompounds
combined to (poly)phenolic compounds could increase the solubility and exert their
potential synergistic antioxidant effects.
The approach proposed consists of preparing the D-ribose derivative 1 to obtain the donor 2 then
employed to produce glycoconjugates containing well known (poly)phenols through a Mitsunobu
reaction.5
To assess the bioactivity of selenoglycoconjugates, DPPH and ABTS antiradical assays were
performed, while the effects on cell proliferation were preliminarily investigated on SH-SY5Y
cells. The phenol moiety greatly affected both the antiradical efficacy and the mitochondrial redox
activity. The glycoconjugates, especially at the highest tested concentrations, exhibited cytotoxic
effects lower than that of unconjugated phenolic compounds, underlining the mitigating impact of
selenosugar
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