13 results on '"E Maccioni"'
Search Results
2. Investigating the Anticancer Activity of Isatin/Dihydropyrazole Hybrids.
- Author
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Meleddu R, Petrikaite V, Distinto S, Arridu A, Angius R, Serusi L, Škarnulytė L, Endriulaitytė U, Paškevičiu Tė M, Cottiglia F, Gaspari M, Taverna D, Deplano S, Fois B, and Maccioni E
- Abstract
A series of isatin-dihydropyrazole hybrids have been synthesized in order to assess their potential as anticancer agents. In particular, 12 compounds were evaluated for their antiproliferative activity toward A549, IGR39, U87, MDA-MB-231, MCF-7, BT474, BxPC-3, SKOV-3, and H1299 cell lines, and human foreskin fibroblasts. Four compounds exhibited interesting antiproliferative activity and were further examined to determine their EC
50 values toward a panel of selected tumor cell lines. The best compounds were then investigated for their induced mechanism of cell death. Preliminary structure-activity relationship indicates that the presence of a substituent such as a chlorine atom or a methyl moiety in position 5 of the isatin nucleus is beneficial for the antitumor activity. EMAC4001 proved the most promising compound within the studied series with EC50 values ranging from 0.01 to 0.38 μM., Competing Interests: The authors declare no competing financial interest.- Published
- 2018
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3. Identification of Myricetin as an Ebola Virus VP35-Double-Stranded RNA Interaction Inhibitor through a Novel Fluorescence-Based Assay.
- Author
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Daino GL, Frau A, Sanna C, Rigano D, Distinto S, Madau V, Esposito F, Fanunza E, Bianco G, Taglialatela-Scafati O, Zinzula L, Maccioni E, Corona A, and Tramontano E
- Subjects
- Ebolavirus drug effects, Hemorrhagic Fever, Ebola drug therapy, Hemorrhagic Fever, Ebola virology, Humans, Molecular Docking Simulation, Plumbaginaceae chemistry, Protein Conformation, RNA, Double-Stranded genetics, RNA, Double-Stranded metabolism, RNA, Viral genetics, RNA, Viral metabolism, Viral Regulatory and Accessory Proteins genetics, Viral Regulatory and Accessory Proteins metabolism, Antiviral Agents pharmacology, Flavonoids pharmacology, Fluorescence, Plant Extracts pharmacology, RNA, Double-Stranded antagonists & inhibitors, RNA, Viral antagonists & inhibitors, Viral Regulatory and Accessory Proteins antagonists & inhibitors
- Abstract
Ebola virus (EBOV) is a filovirus that causes a severe and rapidly progressing hemorrhagic syndrome; a recent epidemic illustrated the urgent need for novel therapeutic agents because no drugs have been approved for treatment of Ebola virus. A key contribution to the high lethality observed during EBOV outbreaks comes from viral evasion of the host antiviral innate immune response in which viral protein VP35 plays a crucial role, blocking interferon type I production, first by masking the viral double-stranded RNA (dsRNA) and preventing its detection by the pattern recognition receptor RIG-I. Aiming to identify inhibitors of the interaction of VP35 with the viral dsRNA, counteracting the VP35 viral innate immune evasion, we established a new methodology for high-yield recombinant VP35 (rVP35) expression and purification and a novel and robust fluorescence-based rVP35-RNA interaction assay ( Z' factor of 0.69). Taking advantage of such newly established methods, we screened a small library of Sardinian natural extracts, identifying Limonium morisianum as the most potent inhibitor extract. A bioguided fractionation led to the identification of myricetin as the component that can inhibit rVP35-dsRNA interaction with an IC
50 value of 2.7 μM. Molecular docking studies showed that myricetin interacts with the highly conserved region of the VP35 RNA binding domain, laying the basis for further structural optimization of potent inhibitors of VP35-dsRNA interaction.- Published
- 2018
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4. Tuning the Dual Inhibition of Carbonic Anhydrase and Cyclooxygenase by Dihydrothiazole Benzensulfonamides.
- Author
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Meleddu R, Distinto S, Cottiglia F, Angius R, Gaspari M, Taverna D, Melis C, Angeli A, Bianco G, Deplano S, Fois B, Del Prete S, Capasso C, Alcaro S, Ortuso F, Yanez M, Supuran CT, and Maccioni E
- Abstract
A novel series of of 4-[(3-phenyl-4-aryl-2,3-dihydro-1,3-thiazol-2-ylidene)amino]benzene-1-sulfonamides ( EMAC10111a-g ) was synthesized and assayed toward both human carbonic anhydrase isozymes I, II, IX, and XII and cyclooxygenase isoforms. The majority of these derivatives preferentially inhibit hCA isoforms II and XII and hCOX-2 isozyme, indicating that 2,3,4-trisubstituted 2,3-dihydrothiazoles are a promising scaffold for the inhibition of hCA isozymes and of hCOX-2 enzyme. The nature of the substituent at the dihydrothiazole ring position 4 influenced the activity and selectivity toward both enzyme families. EMAC10111g resulted as the best performing compound toward both enzyme families and exhibited preferential activity toward hCA XII and hCOX-2 isozymes., Competing Interests: The authors declare no competing financial interest.
- Published
- 2018
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5. Targeting Tumor Associated Carbonic Anhydrases IX and XII: Highly Isozyme Selective Coumarin and Psoralen Inhibitors.
- Author
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Melis C, Distinto S, Bianco G, Meleddu R, Cottiglia F, Fois B, Taverna D, Angius R, Alcaro S, Ortuso F, Gaspari M, Angeli A, Del Prete S, Capasso C, Supuran CT, and Maccioni E
- Abstract
A small library of psoralen carboxylic acids and their corresponding benzenesulfonamide derivatives were designed and synthesized to evaluate their activity and selectivity toward tumor associated human carbonic anhydrase (hCA) isoforms IX and XII. Both psoralen acids and sulfonamides exhibited potent inhibition of IX and XII isozymes in the nanomolar concentration range. However, psoralen acids resulted as the most selective in comparison with the corresponding benzenesulfonamide derivatives. Our data indicate that the psoralen scaffold is a promising starting point for the design of highly selective tumor associated hCA inhibitors., Competing Interests: The authors declare no competing financial interest.
- Published
- 2018
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6. N -Acylbenzenesulfonamide Dihydro-1,3,4-oxadiazole Hybrids: Seeking Selectivity toward Carbonic Anhydrase Isoforms.
- Author
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Bianco G, Meleddu R, Distinto S, Cottiglia F, Gaspari M, Melis C, Corona A, Angius R, Angeli A, Taverna D, Alcaro S, Leitans J, Kazaks A, Tars K, Supuran CT, and Maccioni E
- Abstract
A series of N -acylbenzenesulfonamide dihydro-1,3,4-oxadiazole hybrids ( EMAC8000a-m ) was designed and synthesized with the aim to target tumor associated carbonic anhydrase (hCA) isoforms IX and XII. Most of the compounds were selective inhibitors of the tumor associated hCA XII. Moreover, resolution of EMAC8000d racemic mixture led to the isolation of the levorotatory eutomer exhibiting an increase of hCA XII inhibition potency and selectivity with respect to hCA II. Computational studies corroborated these data. Overall our data indicate that both substitution pattern and stereochemistry of dihydro-1,3,4-oxadiazole could be considered as key factors to determine activity and selectivity toward hCA isozymes. These results can provide further indication for the design and optimization of selective hCA inhibitors.
- Published
- 2017
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7. Identification and characterization of new DNA G-quadruplex binders selected by a combination of ligand and structure-based virtual screening approaches.
- Author
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Alcaro S, Musetti C, Distinto S, Casatti M, Zagotto G, Artese A, Parrotta L, Moraca F, Costa G, Ortuso F, Maccioni E, and Sissi C
- Subjects
- Biophysics, Circular Dichroism, Fluorescence, Furocoumarins chemistry, Ligands, Mass Spectrometry, G-Quadruplexes, Nucleic Acid Conformation
- Abstract
Nowadays, it has been demonstrated that DNA G-quadruplex arrangements are involved in cellular aging and cancer, thus boosting the discovery of selective binders for these DNA secondary structures. By taking advantage of available structural and biological information on these structures, we performed a high throughput in silico screening of commercially available molecules databases by merging ligand- and structure-based approaches by means of docking experiments. Compounds selected by the virtual screening procedure were then tested for their ability to interact with the human telomeric G-quadruplex folding by circular dichroism, fluorescence spectroscopy, and photodynamic techniques. Interestingly, our screening succeeded in retrieving a new promising scaffold for G-quadruplex binders characterized by a psoralen moiety.
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- 2013
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8. 3-Acetyl-2,5-diaryl-2,3-dihydro-1,3,4-oxadiazoles: a new scaffold for the selective inhibition of monoamine oxidase B.
- Author
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Maccioni E, Alcaro S, Cirilli R, Vigo S, Cardia MC, Sanna ML, Meleddu R, Yanez M, Costa G, Casu L, Matyus P, and Distinto S
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- Animals, Cell Line, Drug Design, Humans, Insecta cytology, Isoenzymes antagonists & inhibitors, Models, Molecular, Monoamine Oxidase Inhibitors chemistry, Monoamine Oxidase Inhibitors pharmacology, Oxadiazoles chemistry, Oxadiazoles pharmacology, Protein Binding, Recombinant Proteins antagonists & inhibitors, Stereoisomerism, Structure-Activity Relationship, Monoamine Oxidase Inhibitors chemical synthesis, Oxadiazoles chemical synthesis
- Abstract
3-Acetyl-2,5-diaryl-2,3-dihydro-1,3,4-oxadiazoles were designed, synthesized, and tested as inhibitors against human monoamine oxidase (MAO) A and B isoforms. Several compounds, obtained as racemates, were identified as selective MAO-B inhibitors. The enantiomers of some derivatives were separated by enantioselective HPLC and tested. The R-enantiomers always showed the highest activity. Docking study and molecular dynamic simulations demonstrated the putative binding mode. We conclude that these 1,3,4-oxadiazoles derivatives are promising reversible and selective MAO-B inhibitors.
- Published
- 2011
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9. A novel histone acetyltransferase inhibitor modulating Gcn5 network: cyclopentylidene-[4-(4'-chlorophenyl)thiazol-2-yl)hydrazone.
- Author
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Chimenti F, Bizzarri B, Maccioni E, Secci D, Bolasco A, Chimenti P, Fioravanti R, Granese A, Carradori S, Tosi F, Ballario P, Vernarecci S, and Filetici P
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- Acetylation, Catalysis, Enzyme Inhibitors chemistry, Glutamic Acid genetics, Histone Acetyltransferases drug effects, Histone Acetyltransferases genetics, Histone Acetyltransferases metabolism, Histones metabolism, Hydrazones chemistry, Mutation, Saccharomyces cerevisiae Proteins genetics, Saccharomyces cerevisiae Proteins metabolism, Thiazoles chemistry, Enzyme Inhibitors pharmacology, Histone Acetyltransferases antagonists & inhibitors, Hydrazones pharmacology, Saccharomyces cerevisiae Proteins drug effects, Thiazoles pharmacology
- Abstract
Acetylation is a key modulator of genome accessibility through decondensation of the chromatin structure. The balance between acetylation and opposite deacetylation is, in fact, a prerequisite for several cell functions and differentiation. To find modulators of the histone acetyltransferase Gcn5p, we performed a phenotypic screening on a set of newly synthesized molecules derived from thiazole in budding yeast Saccharomyces cerevisiae. We selected compounds that induce growth inhibition in yeast strains deleted in genes encoding known histone acetyltransferases. A novel molecule CPTH2, cyclopentylidene-[4-(4'-chlorophenyl)thiazol-2-yl)hydrazone, was selected based on its inhibitory effect on the growth of a gcn5Delta strain. We demonstrated a specific chemical-genetic interaction between CPTH2 and HAT Gcn5p, indicating that CPTH2 inhibits the Gcn5p dependent functional network. CPTH2 inhibited an in vitro HAT reaction, which is reverted by increasing concentration of histone H3. In vivo, it decreased acetylation of bulk histone H3 at the specific H3-AcK14 site. On the whole, our results demonstrate that CPTH2 is a novel HAT inhibitor modulating Gcn5p network in vitro and in vivo.
- Published
- 2009
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10. Synthesis, stereochemical identification, and selective inhibitory activity against human monoamine oxidase-B of 2-methylcyclohexylidene-(4-arylthiazol-2-yl)hydrazones.
- Author
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Chimenti F, Maccioni E, Secci D, Bolasco A, Chimenti P, Granese A, Carradori S, Alcaro S, Ortuso F, Yáñez M, Orallo F, Cirilli R, Ferretti R, and La Torre F
- Subjects
- Chromatography, High Pressure Liquid, Cyclohexanones chemistry, Humans, Hydrazones chemistry, Hydrazones pharmacology, Inhibitory Concentration 50, Monoamine Oxidase drug effects, Monoamine Oxidase Inhibitors chemistry, Monoamine Oxidase Inhibitors pharmacology, Stereoisomerism, Thermodynamics, Thiazoles chemistry, Thiazoles pharmacology, Thiosemicarbazones chemistry, Hydrazones chemical synthesis, Monoamine Oxidase metabolism, Monoamine Oxidase Inhibitors chemical synthesis, Thiazoles chemical synthesis
- Abstract
A series of 2-methylcyclohexylidene-(4-arylthiazol-2-yl)hydrazones have been investigated for their ability to inhibit selectively the activity of the human A and B isoforms of monoamine oxidase (MAO). The target compounds, which present a stereogenic center on the cyclohexane ring, were obtained as pure (R) and (S) enantiomers by enantioselective HPLC. The absolute configuration of homochiral forms isolated on a semipreparative scale was obtained by a combined strategy based on chemical correlation and single-crystal X-ray diffraction. All compounds showed higher activity against the human MAO-B isoform with IC50 values ranging between 26.81 +/- 2.74 microM and 14.20 +/- 0.26 nM, and the assays carried out on the pure enantiomers showed higher activity for the (R) form. A computational study was performed by molecular mechanics, DFT-based quantomechanics, and docking techniques on the most active and human MAO-B selective inhibitor 8.
- Published
- 2008
- Full Text
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11. Selective inhibitory activity against MAO and molecular modeling studies of 2-thiazolylhydrazone derivatives.
- Author
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Chimenti F, Maccioni E, Secci D, Bolasco A, Chimenti P, Granese A, Befani O, Turini P, Alcaro S, Ortuso F, Cardia MC, and Distinto S
- Subjects
- Hydrazones chemistry, Isoenzymes chemical synthesis, Isoenzymes chemistry, Molecular Conformation, Monoamine Oxidase Inhibitors chemistry, Structure-Activity Relationship, Thiazoles chemistry, Hydrazones chemical synthesis, Models, Molecular, Monoamine Oxidase chemistry, Monoamine Oxidase Inhibitors chemical synthesis, Thiazoles chemical synthesis
- Abstract
A series of 2-thiazolylhydrazone derivatives have been investigated for the ability to inhibit the activity of the A and B isoforms of monoamine oxidase (MAO) selectively. All of the compounds showed high activity against both the MAO-A and the MAO-B isoforms with pKi values ranging between 5.92 and 8.14 for the MAO-A and between 4.69 and 9.09 for the MAO-B isoforms. Both the MAO-A and the MAO-B isoforms, deposited in the Protein Data Bank as model 2BXR and 1GOS, respectively, were considered in a computational study performed with docking techniques on the most active and MAO-B-selective inhibitor, 18.
- Published
- 2007
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12. Synthesis, molecular modeling studies, and selective inhibitory activity against monoamine oxidase of 1-thiocarbamoyl-3,5-diaryl-4,5-dihydro-(1H)- pyrazole derivatives.
- Author
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Chimenti F, Maccioni E, Secci D, Bolasco A, Chimenti P, Granese A, Befani O, Turini P, Alcaro S, Ortuso F, Cirilli R, La Torre F, Cardia MC, and Distinto S
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- Binding Sites, Chromatography, High Pressure Liquid, Crystallography, X-Ray, Monoamine Oxidase Inhibitors chemistry, Monte Carlo Method, Protein Binding, Pyrazoles chemistry, Quantitative Structure-Activity Relationship, Stereoisomerism, Thiocarbamates chemistry, Models, Molecular, Monoamine Oxidase chemistry, Monoamine Oxidase Inhibitors chemical synthesis, Pyrazoles chemical synthesis, Thiocarbamates chemical synthesis
- Abstract
A novel series of 1-thiocarbamoyl-3,5-diaryl-4,5-dihydro-(1H)-pyrazole derivatives have been synthesized and investigated for the ability to inhibit selectively the activity of the A and B isoforms of monoamine oxidase (MAO). All the synthesized compounds show high activity against both the MAO-A and the MAO-B isoforms with Ki values between 27 and 4 nM and between 50 and 1.5 nM, respectively, except for a few derivatives whose inhibitory activity against MAO-B was in the micromolar range. Knowing that stereochemistry may be an important modulator of biological activity, we performed the semipreparative chromatographic enantioseparation of the most potent, selective, and chiral compounds. The separated enantiomers were then submitted to in vitro biological evaluation. The selectivity of the (-)-(S)-1 enantiomer against MAO-B increases twice and a half, while the selectivity of the (-)-(S)-4 enantiomer against MAO-A triples. Both the MAO-A and MAO-B isoforms respectively of the 1O5W and 1GOS models deposited in the Protein Data Bank were considered in the computational study. The docking study was carried out using several computational approaches with the aim of proposing possible binding modes of the MAO enantioselective compounds 1 and 4.
- Published
- 2005
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13. Influence of Epicuticular Waxes on the Photolysis of Pirimicarb in the Solid Phase.
- Author
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Pirisi FM, Angioni A, Cabizza M, Cabras P, and Maccioni E
- Abstract
The influence of epicuticular waxes extracted from different fruits on the photodegradation of pirimicarb (I) in the solid phase was studied. Waxes were extracted with CHCl(3) and CHCl(3)/CH(3)OH from nectarines (N), oranges (O(R)), and mandarin oranges (M). All of the waxes affect the qualitative behavior of the photodegradation of I: the formation of photoproducts N-formylpirimicarb (II) and demethylpirimicarb (III) was hindered. This influence was found to be independent of the light sources (sunlight or lamp > 290 nm) and of the solvents employed in the extraction of the waxes. The photodegradation rate (K(obs)) of I was reduced to a different extent by the presence of waxes, from N and O, and was increased from M (irrespective of the extraction solvent). The photodegradation rates of II and III were both reduced by all waxes, M included. The waxes extracted with CHCl(3)/CH(3)OH show a higher inhibition effect on K(obs) than those with CHCl(3). The scales of rate reduction were similar under sunlight and artificial light. Inhibition of the photodegradation rate does not correlate with UV absorbance of waxes or with their content on the surface of the fruits.
- Published
- 1998
- Full Text
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