Papers by Paola Massarelli
Journal of Food Composition and Analysis, 2009
Major compounds (i.e. phenolic compounds and carotenoids) were analysed in the extracts of the ed... more Major compounds (i.e. phenolic compounds and carotenoids) were analysed in the extracts of the edible part of three tropical fruits: the Andean blackberry, the naranjilla and the tree tomato. Ellagitannins and anthocyanins were predominant in blackberries and phenolic composition can be used to differentiate the two species studied. Similar phenolic composition occurred in red and yellow tree tomato except for anthocyanins which were absent in the yellow tree tomato. Phenolic acids were detected in the naranjilla pulp. Carotenoids were analysed in the fruits. The composition in carotenoids was similar in the two varieties of tree tomato and their vitamin A activity was calculated. Carotenol fatty acid esters were predominant. b-Cryptoxanthin esters and b-carotene were the major carotenoids. The carotenoid content was high compared to literature data, providing an important high vitamin A activity. In blackberries and naranjilla, this class of compounds was found only at trace level. Finally, ORAC values were estimated in different solvent extracts and results were compared with published data in common fruits.
BMC Cancer, 2022
Background Serotonin (or 5-Hydroxytryptamine, 5-HT) signals in mammary gland becomes dysregulated... more Background Serotonin (or 5-Hydroxytryptamine, 5-HT) signals in mammary gland becomes dysregulated in cancer, also contributing to proliferation, metastasis, and angiogenesis. Thus, the discovery of novel compounds targeting serotonin signaling may contribute to tailor new therapeutic strategies usable in combination with endocrine therapies. We have previously synthesized serotoninergic receptor ligands (SER) with high affinity and selectivity towards 5-HT2A and 5-HT2C receptors, the main mediators of mitogenic effect of serotonin in breast cancer (BC). Here, we investigated the effect of 10 SER on viability of MCF7, SKBR3 and MDA-MB231 BC cells and focused on their potential ability to affect Tamoxifen responsiveness in ER+ cells. Methods Cell viability has been assessed by sulforhodamine B assay. Cell cycle has been analyzed by flow cytometry. Gene expression of 5-HT receptors and Connective Tissue Growth Factor (CTGF) has been checked by RT-PCR; mRNA levels of CTGF and ABC transp...
Con il progesso della medicina e della tecnologia farmaceutica certe formulazioni non sono più di... more Con il progesso della medicina e della tecnologia farmaceutica certe formulazioni non sono più di attualità, relegate solo a lontani ricordi di altri tempi o associate a riti magici e da streghe. L’uso della pozione è infatti calato a causa di diverse ragioni, principalmente per la sua poca stabilità, ma anche per la scarsa capacità dei medici nel formularla e infine per il rimpiazzo con preparati più facilmente allestibili. Tuttavia al giorno d’oggi questa forma farmaceutica, se opportunamente impiegata, può suscitare un nuovo interesse, almeno nel campo della fitoterapia e dell’utilizzo delle piante officinali
ChemInform, 2007
This paper will explore how the often illegal activities of hackers (in the original usage of the... more This paper will explore how the often illegal activities of hackers (in the original usage of the term to refer to individuals who modify computer hardware and software) may produce valuable innovations. It will explore how these innovations, termed Outlaw Innovations, may be appropriated by firms and provide case studies where this has taken place. The paper will seek to locate this phenomenon in the existing innovation literature, and explore the implications for firm innovation processes. It will outline a series of possible research questions and conclude by indicating the next steps in the development of this research.
Journal of Medicinal Chemistry, 2005
New arylpiperazine derivatives were prepared to identify highly selective and potent ligands for ... more New arylpiperazine derivatives were prepared to identify highly selective and potent ligands for the 5-hydroxytryptamine 1A (5-HT 1A) receptor as potential pharmacological tools in studies of central nervous system (CNS) disorders. The combination of structural elements (heterocyclic nucleus, oxyalkyl chain, and arylpiperazine) known to introduce 5-HT 1A receptor affinity and the proper selection of substituents led to compounds with higher receptor specificity and affinity. In binding studies, several molecules showed affinity in the nanomolar and subnanomolar ranges at 5-HT 1A and moderate to no affinity for other relevant receptors (5-HT 2A , 5-HT 2C , D 1 , D 2 , R 1 , and R 2). The 4-[3-[4-(o-methoxyphenyl)piperazin-1-yl]propoxy]-4-aza-tricyclo-[5.2.1.02,6]dec-8-ene-3,5-dione (3b), with K i) 0.021 nM, was the most active and selective derivative for the 5-HT 1A receptor with respect to other serotonin receptors, whereas the most selective derivative for dopaminergic and adrenergic receptors was a CF 3-substituted arylpiperazine (2e). As a general trend, compounds with a piperazinylpropoxy chain (3b-g) showed a preferential affinity for the 5-HT 1A receptor, suggesting that the alkyl chain length represents a critical structural feature in determining 5-HT 1A receptor affinity and selectivity, as confirmed by the molecular modeling invoked for explaining the differential binding affinities of the new arylpiperazines.
European Journal of Medicinal Chemistry, 2010
An easy and convenient microwave-assisted synthesis of a small library of indolic arylpiperazine ... more An easy and convenient microwave-assisted synthesis of a small library of indolic arylpiperazine derivatives is described. Parallel and mixed pool combinatorial methods are reported and compared. The described reactions are nucleophilic substitutions of several aromatic piperazines in presence of K 2 CO 3. Good yields and short reaction times are the main aspect of these procedures. Binding assays shed additional light on the influence of the LCAPs on the 5-HT 1A , 5-HT 2A and 5-HT 2C receptors affinity and allowed to disclose three interesting compounds as 5-HT 2C , mixed 5-HT 2A /5-HT 2C and 5-HT 1A /5-HT 2C ligands (4i, 4l and 4d, respectively), with potential antiepileptic, anxiolytic or atypical antipsychotic agent therapeutical profiles.
European Journal of Medicinal Chemistry, 2011
Serotonin (5-hydroxytryptamine, 5-HT) is one of the most important neuromediator involved in nume... more Serotonin (5-hydroxytryptamine, 5-HT) is one of the most important neuromediator involved in numerous physiological and pathophysiological processes. In addition it is well established that 5-HT acts as a growth factor on several types of non-tumoral and tumoral cells, and recently it was also related to oncogenes. 5-HT1A receptor expression was identified in prostatic tumor cell lines (PC3 cells) and in human hormone refractory prostate cancer tissue. Based on these observations, development of 5-HT1A antagonists could be useful in inhibiting the growth of cancer cells. In order to investigate on potential use of 5-HT1A ligands as antiproliferative agents, we have analyzed a new set of 1-naphtylpiperazine derivatives. In binding studies, several molecules showed affinity in nanomolar and subnanomolar range at 5-HT1A and moderate to no affinity for other relevant receptors (5-HT2A, 5-HT2C, D1, D2, α1 and α2). All compounds were then evaluated in order to assess their antiproliferative activity using PC3 cells and the most active compounds (1 and 2) were fully characterized to define the mechanism responsible for the observed antiproliferative effect.
Bioorganic & Medicinal Chemistry Letters, 2010
European Journal of Medicinal Chemistry, 2012
N 0-cyanopicolinamidine derivatives, linked to an arylpiperazine moiety, were prepared and their ... more N 0-cyanopicolinamidine derivatives, linked to an arylpiperazine moiety, were prepared and their affinity to serotonin 5-HT 1A , 5-HT 2A and 5-HT 2C receptors were evaluated. The combination of structural elements (heterocyclic nucleus, alkyl chain and 4-substituted piperazine) known to be critical for affinity to 5-HT 1A receptors and the proper selection of substituents led to compounds with high specificity and affinity towards serotoninergic receptors. In binding studies, several molecules showed affinity in nanomolar and subnanomolar range at 5-HT 2A and moderate to no affinity for other relevant receptors (5-HT 1A , 5-HT 2C , D 1 , D 2 , a 1 and a 2). N 0-cyano-N-(3-(4-(3-chlorophenyl)piperazin-1-yl)propyl)-picolinamidine (4l) with K i ¼ 0.000185 nM, was the most active and selective derivative for the 5-HT 2A receptor compared to other serotoninergic, dopaminergic and adrenergic receptors.
Journal of Computer-Aided Molecular Design, 2014
Recently developed multi-targeted ligands are novel drug candidates able to interact with monoami... more Recently developed multi-targeted ligands are novel drug candidates able to interact with monoamine oxidase (MAO) A and B; acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE); or with histamine N-methyltransferase (HMT) and histamine H 3-receptor (H 3 R). These proteins are drug targets in the treatment of depression, Alzheimer's disease, obsessive disorders, and Parkinson's disease. A probabilistic method, the Parzen-Rosenblatt Window approach, was used to build a "predictor" model using data collected from the ChEMBL database. The model can be used to predict both the primary pharmaceutical target and off-targets of a compound based on its structure. Molecular structures were represented based on the circular fingerprint methodology. The same approach was used to build a "predictor" model from the DrugBank dataset to determine the main pharmacological groups of the compound. The study of off-target interactions is now recognised as crucial to the understanding of both drug action and toxicology. Primary pharmaceutical targets and off-targets for the novel multi-target ligands were examined by use of the developed cheminformatic method. Several multi-target ligands were selected for further study, as compounds with possible additional beneficial pharmacological activities. The cheminformatic targets identifications were in agreement with four 3D-QSAR (H 3 R/D 1 R/D 2 R/5-HT 2a R) models and by in vitro assays for serotonin 5-HT 1a and 5-HT 2a receptor binding of the most promising ligand (71/MBA-VEG8).
Bioorganic & Medicinal Chemistry
Picolinamide derivatives, linked to an arylpiperazine moiety, were prepared and their affinity to... more Picolinamide derivatives, linked to an arylpiperazine moiety, were prepared and their affinity to 5-HT, 5-HT and 5-HT receptors was evaluated. The combination of structural elements (heterocyclic nucleus, alkyl chain and 4-substituted piperazine), known to play critical roles in affinity for serotoninergic receptors, and the proper selection of substituents led to compounds with high specificity and affinity towards serotoninergic receptors. In binding studies, several molecules showed high affinity in nanomolar and subnanomolar range at 5-HT, 5-HT and 5-HT receptors and moderate or no affinity for other relevant receptors (D, D, α and α). N-(2-(4-(pyrimidin-2-yl)piperazin-1-yl)ethyl)picolinamide (3o) with Ki=0.046nM, was the most affine and selective derivative for the 5-HT receptor compared to other serotoninergic dopaminergic and adrenergic receptors. N-(2-(4-(2-methoxyphenyl)piperazin-1-yl)ethyl)picolinamide (3b), instead, showed a subnanomolar affinity towards 5-HT with Ki=0.0224nM, whereas N-(2-(4-(bis(4-fluorophenyl)methyl)piperazin-1-yl)ethyl)picolinamide (3s) presented an attractive 5-HT affinity with K=0.8nM. Moreover, the compounds having better affinity and selectivity binding profiles towards 5-HT were selected and tested on rat ileum, to determine their effect on 5HT induced contractions. Those more selective towards 5-HT receptors were studied in vivo on several behavioral tests.
Indian Journal of Chemistry Sect B Organic Chemistry Including Medical Chemistry, 2003
Isoindole derivatives Isoindole derivatives R 0140 Synthesis of 4-(1-Oxo-isoindoline)-, 4-(5,6-Di... more Isoindole derivatives Isoindole derivatives R 0140 Synthesis of 4-(1-Oxo-isoindoline)-, 4-(5,6-Dimethoxy-1-oxo-isoindoline) and 4-Acetamido-Substituted Phenoxy-3-amino-propane Derivatives and Their β 1-, β 2-Adrenergic Receptor Binding Studies.-The β-adrenoceptor binding affinity and selectivity of the synthesized compounds (V) are tested. All the tested compounds (V) exhibit better cardioselectivity than the standard cardioselective β-blocker atenolol.
Uploads
Papers by Paola Massarelli