Publications by authors named "Ornella Azzolina"

In this study we addressed the role of chirality in the biological activity of RC-33, recently studied by us in its racemic form. An asymmetric synthesis procedure was the first experiment, leading to the desired enantioenriched RC-33 but with an enantiomeric excess (ee) not good enough for supporting the in vitro investigation. An enantioselective high-performance liquid chromatography (HPLC) procedure was then successfully carried out, yielding both RC-33 enantiomers in amounts and optical purity suitable for the pharmacological study.

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Phytochemical investigation on the Amygdalus lycioides Spach branchelets resulted in the isolation of four chiral flavanones: (2R,3R)-Taxifolin, (2R,3R)-aromadendrin, (S)-5,7,3',5'-tetrahydroxyflavanone and (S)-naringenin. The flavanones were isolated by semi-preparative HPLC, their structures elucidated based on spectroscopic data and their absolute configuration assigned. As a part of our ethnobotanical-directed search for novel TNFα inhibitors, the bioassay-guided fractionation of the n-hexane-acetone (n-Hex-Ac, 1:1 v/v) Amygdalus lycioides Spach branchelets extract was performed.

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Herein we report the synthesis, drug-likeness evaluation, and in vitro studies of new sigma (σ) ligands based on arylalkenylaminic scaffold. For the most active olefin the corresponding arylalkylamine was studied. Novel arylalkenylamines generally possess high σ(1) receptor affinity (K(i) values <25 nM) and good σ(1)/σ(2) selectivity (K(i)σ(2) >100).

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A microwave-assisted HWE olefination process of readily accessible aryl-alkyl ketones has been developed to provide a rapid access to (Z)-3,3-trisubstituted-alpha,beta-unsaturated methyl esters, key building blocks for the synthesis of biologically active compounds.

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In order to investigate the molecular features involved in sigma receptors (sigma-Rs) binding, new compounds based on arylalkylaminoalcoholic, arylalkenyl- and arylalkylaminic scaffolds were synthesized and their affinity towards sigma(1)- and sigma(2)-Rs subtypes was evaluated. The most promising compounds were also screened for their affinity at micro-opioid, delta-opioid and kappa-opioid receptors. Biological results are herein presented and discussed.

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Four peptides corresponding to highly conserved motives within the first two RNA recognition motif-type domains of ELAV proteins were prepared, and their effect on the stability of NOVA-1 and VEGF ELAV-target mRNAs was evaluated. Biological results show that in the presence of phorbol 12-myristate 13-acetate (a PKC activator triggering the ELAV pathway), an equimolar mixture of peptides induces a statistically significant stabilization of the selected transcripts, suggesting a synergic effect of the two stimuli.

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Introduction: The extract of Crataegus monogyna shows sedative, hypotensive, vasodilator and cardio-tonic actions. Although several papers dealing with the extraction of metabolites from Crataegus have been published, the plant productivity in terms of bioactive compounds is not easily understandable as yet.

Objective: To investigate the influence of the extraction mode on the yield of bioactive compounds from Crataegus monogyna Jacq.

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We performed the asymmetric synthesis of four enantiopure benzo[d] isothiazo-3-or 5-yloxypropanolamine derivatives, previously described as competitive antagonists at beta-adrenoceptors. The chemical characterization of each enantiomer was accomplished by (1)H NMR and HPLC/DAD/CD. The direct chromatographic separation of the enantiomers via chiral HPLC was investigated.

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We describe here the synthesis and the binding interaction with sigma(1) and sigma(2) receptors of a series of new benzo[d]oxazol-2(3H)-one derivatives variously substituted on the N-benzyl moiety. The results of binding studies confirm the notion that the benzoxazolone moiety confers preference towards sigma(1) sites and establish that the ability to bind to sigma(1), but not to sigma(2) receptors, is strongly affected by the kind and the position of the substituents introduced in the N-benzyl ring. In fact, compounds with substitutions in para-position with atoms of Cl, H or F or with a CH(3) group exhibit a higher affinity for sigma(1) receptors than the corresponding ortho-substituted compounds.

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In the attempt to develop new sigma ligands we synthesized a series of N-benzyl-3-[1-(4-fluorophenyl)-1H-indol-3-yl]-N-methylpropan-1-amines and N-benzyl-4-[1-(4-fluorophenyl)-1H-indol-3-yl]-N-methylbutan-1-amines variously substituted on the phenyl ring. The displacement percentages of [3H]-DTG and [3H]-(+)-pentazocine determined in rat liver homogenates by these compounds at the fixed 100 nM concentration have been determined as a preliminary evaluation of their sigma1 and sigma2 affinity, respectively. The results suggested that the phenyl substituents may positively modulate, in comparison with the unsubstituted compound, the ability to displace [3H]-DTG from sigma2 sites, whereas the same phenyl substituents reduced the displacement percentages of [3H]-(+)-pentazocine from sigma1 sites.

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A new series of arylalkyl- and alkenylamines was designed, synthesized, and evaluated for binding to sigma(1) and sigma(2) receptors. Many compounds exhibited nanomolar affinity for sigma(1) subtype receptor with good selectivity over sigma(2). A molecular modeling study was conducted in order to rationalize the experimental data, and the structure-receptor affinities are discussed.

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The diastereoselective synthesis via Grignard reaction of enantiopure analgesic naphthylaminoalcohols has been performed. The chiral racemic key intermediate 3-dimethylamino-2-methyl-1-(naphthalen-2-yl)propan-1-one and enantiomers were prepared and transformed into the desired compounds by addition of the organometallic reagent. The chemical characterization of all diastereoisomers was accomplished by 1H NMR and HPLC analyses and the absolute configuration assigned by CD spectroscopy.

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We describe the preparation of racemic N,N-dimethyl-3-(naphthalen-2-yl)-butan-1-amines, potential sigma1 ligands, and their resolution via chiral HPLC. In order to obtain enantiopure compounds, direct chromatographic methods of separation using chiral stationary phases were investigated. Different methods suitable for both analytical and semipreparative purposes are proposed.

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The preparation and biological evaluation of a new class of arylpyrrolidinols is reported. The antinociceptive activity was evaluated in vivo with the hot plate test (HPT) and formalin test (FT), excluding any involvement on motor coordination with the rota-rod test (RRT). The nociceptive behavior in the late phase of FT (representative of chronic pain) suggests an involvement of the antiinflammatory process and it is clearly influenced by the stereochemical features, being the eutomer of phenylpyrrolidinols, the (2R,3S) enantiomer.

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In the present paper, we report on the synthesis and antinociceptive activity of a new series of N-methyl-arylpyrrolidinols that we designed for a rational structure-activity relationship (SAR) study. The antinociceptive properties were investigated in vivo by the hot plate and formalin tests in mice and control on the locomotory activity was also monitored by the rota rod test. With this aim, the evaluation of the lipophilicity of all compounds was performed by the Daylight computational method in order to better understand the SAR.

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The synthesis and biological evaluation of a series of new derivatives of 2-substituted 5-phenyl-1,4-benzodiazepines, structurally related to tifluadom (5), are reported. Chemical and pharmacological studies on compounds 6 have been pursued with the aim of expanding the SAR data and validating the previously proposed model of interaction of this class of compounds with the kappa-opioid receptor. The synthesis of the previously described compounds 6 has been reinvestigated in order to obtain a more direct synthetic procedure.

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