Tricyclic pyrazoles: synthesis and biological evaluation of novel 4,5-dihydrobenzo-1h-6-oxa-cyclohepta[1,2-c] pyrazole-based analogues of the cannabinoid antagonist ness 0327

We report in this poster the synthesis and in vitro evaluation of novel 4,5- dihydrobenzo-1H-6-oxa-cyclohepta[1,2-c]pyrazoles 1Cb-l variously substituted in position 3

An Overview on different classes of viral entry and Respiratory Syncitial Virus (RSV) fusion inhibitors

The therapeutic approach to AIDS is based on the combination of different drugs in the highly active antiretroviral therapy (HAART) regimen. These drugs have a wide variety of side effects, and some strains of HIV can develop resistance: for these reasons new anti-HIV drugs are needed. In the wide field of anti-HIV medicine this review covers different classes of drugs which inhibit viral entry: in particular the classification of main categories, their mode of action and some new candidates for AIDS therapy are contemplated. Also covered in this review are respiratory syncytial virus (RSV) fusion inhibitors

Synthesis of 3,6-diazabicyclo[3.1.1]heptanes as novel ligands for neuronal nicotinic acetylcholine receptors

Α series of novel 3,6-diazabicyclo[3.1.1]heptane derivatives 4a–f was synthesized and their affinity and selectivity towards α4β2 and α7 nAChR subtypes were evaluated. The results of the current study revealed a number of compounds (4a, 4b and 4c) having a very high affinity for α4β2 (Ki at α4β2 ranging from 0.023 to 0.056 nM) versus α7 nAChR subtypes; among these compounds, the 3-(6-bromopyridin-3-yl)-3,6-diazabicyclo[3.1.1]heptane 4c was found to be the most α7α4β2 selective term in receptor binding assays (α7α4β2 = 1295). Moreover, compound 4d also had high affinity for the α4β2 nAChR subtype (Ki = 1.2 nM) with considerably high selectivity (α7/α4β2 = 23300)

Diamo qualità alla vita: completamento dell'offerta di medicina del dolore e Cure Palliative pediatriche specialistiche in Regione Liguria

il poster dal titolo " Diamo qualità alla vita: completamento dell'offerta di medicina del dolore e Cure Palliative pediatriche specialistiche in Regione Liguria" illustra i risultati ottenuti nella Regione Liguria in materia di cure palliative pediatriche rispetto al quale si colloca la propria attività di consulenza tecnico-scientifica per la realizzazione dell’hospice pediatrico condotta in ambito multidisciplinare attraverso l’accordo tra la Fondazione Maruzza Lefebvre d’Ovidio Onlus e l’Istituto Gaslini

Synthesis, modelling, and antimitotic properties of tricyclic systems characterised by a 2-(5-Phenyl-1<i>H</i>-pyrrol-3-yl)-1,3,4-oxadiazole moiety

Antitumour activity was observed in a series of tricyclic compounds characterised by a 2-(1H-pyrrol-3-yl)-1,3,4-oxadiazole moiety with various substitutions. Their synthesis and antiproliferative activity toward a panel of human tumour cell lines is described. The most interesting compounds 1  c and 4 c were selected for further evaluation to elucidate their possible mechanism of action. Interesting antitumour activity was observed in a series of tricyclic compounds characterised by the presence of a 2-(1H-pyrrol-3-yl)-1,3,4-oxadiazole moiety that is variously substituted. Their synthesis and antiproliferative activity toward a panel of human tumour cell lines is described. The two most interesting compounds were selected for further evaluation to elucidate their possible mechanism of action. Analysis of cell cycle, tubulin polymerisation, modulation of mitotic markers of the M phase, and apoptosis showed that antimitotic activity is the primary mechanism of the cytotoxic effects of these compounds. Experiments performed on isolated tubulin confirmed that the compounds act by inducing tubulin polymerisation, like taxanes. The binding model against tubulin was also examined by molecular modelling and docking. The results support the proposed binding model, which is able to explain the activity of the oxadiazole derivatives on the basis of their docking energy.</br

Synthesis, Modelling, and Antimitotic Properties of Tricyclic Systems Characterised by a 2-(5-Phenyl-1H-pyrrol-3-yl)-1,3,4-oxadiazole Moiety

Interesting antitumor activity was observed in a series of tricyclic compounds characterized by the presence of a 2-(1H-pyrrol-3-yl)-1,3,4-oxadiazole moiety variously substituted. Their synthesis and their antiproliferative activity on a panel of human tumor cell lines is described. The most interesting compounds 1c and 4c were selected for further evaluation in order to understand their possible mechanism of action. Analysis of cell cycle, tubulin polymerization, modulation of mitotic markers of M phase and apoptosis showed that the antimitotic activity is the primary mechanism of their cytotoxic effects. The experiment performed on isolated tubulin confirm that the compounds act by inducing tubulin polymerization, like taxanes. The binding model against tubulin was also examined by molecular modeling and docking. The results point out that the proposed binding model is able to explain the oxadiazole derivatives activity on the basis of their docking energ

Synthetic applications of chiral unsaturated epoxy alcohols prepared by sharpless asymmetric epoxidation

An overview of the synthesis and applications of chiral 2,3-epoxy alcohols containing unsaturated chains is presented. One of the fundamental synthetic routes to these compounds is Sharpless asymmetric epoxidation, which is reliable, highly chemoselective and enables easy prediction of the product enantioselectivity. Thus, unsaturated epoxy alcohols are readily obtained by selective oxidation of the allylic double bond in the presence of other carbon-carbon double or triple bonds. The wide availability of epoxy alcohols with unsaturated chains, the versatility of the epoxy alcohol functionality (e.g. regio- and stereo-selective ring opening; oxidation; and reduction), and the arsenal of established alkene chemistries, make unsaturated epoxy alcohols powerful starting materials for the synthesis of complex targets such as biologically active molecules. The popularization of ring-closing metathesis has further increased their value, making them excellent precursors to cyclic compounds

Synthesis and cytotoxicity of novel hexahydrothieno-cycloheptapyridazinone derivatives

Designed as a new group of tricyclic molecules containing the thienocycloheptapyridazinone ring system, a number of 2N-substituted-hexahydrothieno-cycloheptapyridazinone derivatives were synthesized and their biological activity evaluated. Among the synthesized compounds, derivatives 7d and 7h were found to possess cytotoxic activity against non-small cell lung cancer and central nervous system cancer cell lines, respectively