95 results on '"R. Morigi"'
Search Results
2. Targeting human telomeric and promoter G-quardruplexes: synthesis, biophysical and biological studies of new guanylhydrazones as potential antitumor agents
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R. Morigi, J. Amato, N. Iaccarino, B. Pagano, A. Locatelli, A. Leoni, M. Rambaldi, G. Miglietta, J. Marinello, G. Capranico, E. Novellino, A. Randazzo, and R. Morigi, J. Amato, N. Iaccarino, B. Pagano, A. Locatelli, A. Leoni, M. Rambaldi, G. Miglietta, J. Marinello, G. Capranico, E. Novellino, A. Randazzo
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G-quadruplex, ligands, anticancer, telomers, oncogenes - Published
- 2018
3. Toward the development of specific G-quadruplex binders: biophysical studies of new hydrazone derivatives
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N. Iaccarino, J. Amato, R. Morigi, A. Pagano, A. De Magis, G. Capranico, A. Locatelli, A. Graziadio, A. Leoni, M. Rambaldi, E. Novellino, S. Neidle, B. Pagano, A. Randazzo., and N. Iaccarino, J. Amato, R. Morigi, A. Pagano, A. De Magis, G. Capranico, A. Locatelli, A. Graziadio, A. Leoni, M. Rambaldi, E. Novellino, S. Neidle, B. Pagano, A. Randazzo.
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G-quadruplex, ligands, antitumor - Published
- 2017
4. G-quadruplex binders cause DNA damage by inducing R loops in human cancer cells
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A. De Magis, S. G. Manzo, J. Marinello, R. Morigi, M. Rambaldi, O. Sodet, G. Capranico., and A. De Magis, S. G. Manzo, J. Marinello, R. Morigi, M. Rambaldi, O. Sodet, G. Capranico.
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R-loops, G-Quadruplex, ligands, DNA damage - Published
- 2017
5. Epidemiology of Avoidable Delay in the Care of Patients With Acute Myocardial Infarction in Italy
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A. Tralli, M. Miccoli, A. Merighi, M. A. Tori, R. Bonatti, A. Colasanto, A. Millo, C. Gualtierotti, D. Bongiorni, O. Maltauro, F. Rossato, A. Battaglini, S. De Michelis, C. Pomati, F. Pignatti, S. Firenze, G. Micheli, C. Barberini, L. Tavazzi, B. Cuffiani, A. Verrienti, E. Salmoirago, G. Giuli, A. Rosas, G. Liguori, L. Calabrese, L. Anselmi, C. Cannova, C. Cernetti, W. Lintner, F. Casalone, G. Cecchetto, F. R. Piantadosi, P. Fedel, P. Di Pasquale, F. Pedrazzini, L. Gandini, A. Zussino, R. Gatti, G. Bonizzato, M. Vincenzi, S. Giustiniani, M. G. Vitrano, G. Di Biase, S. Sesti, A. Bianchi, A. Maggi, A. Maresta, G. Di Marco, R. Gastaldillo, C. Parchi, M. R. Pagni, V. Cuzzato, F. Valagussa, G. Straneo, E. Bottari, A. Bianco, R. Mangia, C. Isaia, L. Arcari, L. Di Giusto, P. Catelli, C. Martines, D. Messina, C. Bellet, A. Teston, M. T. Savoia, L. Cacciavillani, S. Ghirardo, G. De Rinaldis, F. Zanin, G. Clivio, L. Sartorelli, G. Invernizzi, D. Caporicci, C. De Vita, D. Balboni, G. A. Bianco, F. Dal Pra, M. Rolt, G. Tirella, F. Coveri, A. Politi, A. Buonomo, D. Guiducci, M. De Thomatis, G. Tumiotto, F. Guidetti, F. Giordano, A. Rosi, N. D'Amato, R. Sandri, A. Zammarchi, P. Losa, G. Di Salvo, M. Viglianco, C. Marchini, S. Ricobono, S. Distante, S. Isola, E. Conti, M. Negrini, P. Ginevrino, P. Zonzin, M. Abrate, D. Torta, R. Zibra, C. A. Caratti, M. Barbiero, L. Rossi, C. Filippi, A. Bertoli, L. Vigani, U. Striano, A. Izzo, F. Bacchilega, G. Ruggeri, S. Mangiameli, M. Jori, E Levati, E. Lepore, A. Parigi, F. Del Citerna, G. Ventura, G. Spataro, A. Alvino, F. Colantoni, F. Bobba, A. Giomi, S. Salituri, F. Formenti, D. Simioni, P. Giani, N. Codromaz, F. Ferrari, L. Papi, C. Belli, D. Rotiroti, C. Zanini, P. Olzeri, M. R. Morigi, L. Libutti, A. Stuto, G. Carniel, M. Palmieri, S. Formentelli, R. Carola, A. M. Andriolo, F. Montanar, I. Rossi, P. Zardini, F. Daleno, M. Sanguinetti, O. M. Camerata, E. Babini, S. Dalla Volta, A. Storelli, F. Barbaresi, A. P. Maggioni, M. G. Franzosi, S. Gramenzi, F. Plastina, L. Iacopetti, D. Di Gregorio, A. Cuda, B. Brinzi, F. Mileto, L. Bordin, V. Sperandeo, M. G. Calistri, C. De Luca, F. Sauro, E. Correale, G. Mauro, L. Santoro, P. Del Bene, E. Cristallo, L. Muzio, L. Bertolo, G. Zunino, P. Maiolino, G. Bellanca, D. Criscitiello, A. M. Zotti, M. Zaninati, A. Mannarini, M. Valentino, I. Santoni, C. Vecchio, E. Sartori, R. Di Zurio, G. M. Pepe, B. Ravera, F. Leo, G. Pettinati, E. Nicolis, R. Acquadro, R. La Spina, S. Nava, R. Scola Gagliardi, G. A. Feruglio, U. Bugatti, A. Contorno, I. Rovida, G. Cellamare, E. Braito, P. Ferraguto, C. L. Moriggi, P. Pellegrini, G. Turci, G. Bonasia, G. Riva, P. Di Nardo, V. Marcarini, G. Zanzani, R. Garbin, G. Basetti, M. Zanardi, C. Cervasel, S. Ciricugno, A. Alberti, D. Zanuttini, V. Ricciardiello, M. Piva, G. Misuraca, D. Niccolini, A. Sanson, F. Bovenzi, R. Rolandi, V. Casartelli, R. Rigo, G. Frigo, M. Mellini, A. Sandri, M. Fuso, C. Fresco, A. Lotto, M. V. De Simone, G. Poggio, A. Battistello, D. De Matteis, R. Borsoni, A. Gruosso, A. Ferro, F. Balestra, E. Cinà, A. Pennetta, M. Valsecchi, M. Ravani, G. F. Parenti, F. Zeni, R. Negro, M. Martinuzzi, G. T. Sicca, G. Ragazzini, A. Di Benedetto, G. C. Lavezzaro, G. Fonzi, M. Colabene, T. Lanzetta, D. Riva, L. Riggi, B. Lomanto, S. Rizzatello, S. Celada, E. Bariselli, E. Colla, R. Gorni, L. Orselli, E. Bonfanti, D. Fenzi, V. De Petra, A. Perotti, C. De Ponti, G. Rondinelli, M. G. Zatti, R. Puntin, A. Pattarello, D. Cotti, N. Baldassari, A. Ferrante, R. Croci, F. Pigato, A. Fabbri, R. Carlon, D. Mereu, E. Geraci, M. Malavasi, G. Tognoni, S. Signorelli, V. Milli, M. G. Boriassi, P. Mari, F. Rossi, A. Villella, U. Conti, L. Zilli, P. Rossi, A. Muscolino, P. Pascotto, L. D'Aniello, G. Masini, U. Gazzola, F. Passoni, and L. Colonna
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medicine.medical_specialty ,business.industry ,Potential risk ,Psychological intervention ,Infarction ,medicine.disease ,Diabetes mellitus ,Epidemiology ,Emergency medicine ,Internal Medicine ,Coronary care unit ,Medicine ,Myocardial infarction ,business ,Intensive care medicine - Abstract
Background: The delay between onset of symptoms and coronary care unit admission is decisive in the outcome of patients with acute myocardial infarction. Objective: To evaluate the influence of the factors that affect the delay in acute myocardial infarction treatment. Methods: Multicenter case-control study conducted by 118 coronary care units in Italy. The median and mean times in cases and controls were compared for decision time, home-to-hospital time, and in-hospital time, and the influence of several potential risk factors on the delay was evaluated by comparison of patients admitted more than 6 hours after onset with those admitted within 6 hours after onset. Results: Among 5301 patients with acute myocardial infarction, 590 who came to a coronary care unit after 12 hours were considered cases. Controls included 600 patients treated within 2 hours, 603 between 2 and 6 hours, and 466 between 6 and 12 hours. The median decision time among cases was 50-fold higher than that of controls who presented within 2 hours. Home-to-hospital time and in-hospital time appeared to play a less important role. Among the patient-related variables, advanced age, living alone, low intensity of initial symptoms, history of diabetes, strong pain at onset of the infarction, occurrence of symptoms at night, and involvement of a general practitioner seemed to affect delay significantly. Conclusion: Interventions aimed at reducing the delay in acute myocardial infarction treatment should primarily focus on the help-seeking behavior of patients. (Arch Intern Med. 1995;155:1481-1488)
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- 1995
6. Capitolo 12. Metodi spettrometrici
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Roberto Mandrioli, Laura Mercolini, Michele Protti, G. Boatto, I. Briguglio, A. Brizzi, E. Calleri, A. Carrieri, G. Fracchiolla, P. Gratteri, R. Mandrioli, C. Manera, G. Massolini, L. Mercolini, R. Morigi, M. Nalli, S. Orlandini, M. Protti, A. Carrieri, and Roberto Mandrioli, Laura Mercolini, Michele Protti
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Analisi farmaceutica ,UV-Vi ,Spettrofluorimetria ,Assorbimento atomico ,MS ,Emissione atomica ,Analisi quantitativa ,Spettrometria - Abstract
Prendono il nome di tecniche spettrometriche tutti quei metodi d'analisi che si basano su misurazioni di effetti dovuti all'interazione tra la materia e un'opportuna radiazione elettromagnetica (EM). Fa eccezione a questa definizione la spettrometria di massa (mass spectrometry, MS) che, nonostante il nome, non è una tecnica spettroscopica, in quanto non fa uso di radiazioni elettromagnetiche. L'MS deve il suo nome di "spettrometria" a ragioni storiche, e perciò sarà comunque trattata all'interno di questo capitolo. Per quanto riguarda le analisi quantitative in ambito farmaceutico, le radiazioni di gran lunga più utilizzate sono quelle che corrispondono agli intervalli dell’UV e del visibile (UV-Vis), in quanto si tratta di radiazioni con energia corrispondente a quella di legame covalente, quindi capaci di eccitare elettroni di valenza di molecole organiche e di singoli atomi. Radiazioni IR sono utilizzate soprattutto per scopi qualitativi, in quanto in grado di influenzare le vibrazioni dei legami molecolari covalenti; i raggi X sono utilizzati invece per l’analisi elementare e cristallografica, soprattutto in ambito inorganico.
- Published
- 2019
7. Imidazo[2,1-b]thiazole guanylhydrazones as RSK2 inhibitors
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Aldo Andreani, Alessandra Locatelli, Lucilla Varoli, Massimiliano Granaiola, Alberto Leoni, Robert H. Shoemaker, Sudhir Kondapaka, Mirella Rambaldi, Jeffrey S. Smith, Rita Morigi, Dominic A. Scudiero, Deborah A. Lannigan, A. Andreani, M. Granaiola, A. Leoni, A. Locatelli, R. Morigi, M. Rambaldi, L. Varoli, D. Lannigan, J. Smith, D. Scudiero, S. Kondapaka, and R. H. Shoemaker
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Magnetic Resonance Spectroscopy ,Spectrophotometry, Infrared ,Glycogen Synthase Kinase 3 ,chemistry.chemical_compound ,GUANYLHYDRAZONES ,Cell Line, Tumor ,Drug Discovery ,Humans ,Enzyme Inhibitors ,Kinase activity ,Thiazole ,Pharmacology ,Chemistry ,Kinase ,Ribosomal Protein S6 Kinases ,Organic Chemistry ,Hydrazones ,IMIDAZO[21-b]THIAZOLES ,RSK2 ,General Medicine ,Nuclear magnetic resonance spectroscopy ,In vitro ,ANTITUMOR ACTIVITY ,Biomarker ,Biochemistry ,Cell culture ,Drug Screening Assays, Antitumor ,INHIBITORS ,Selectivity - Abstract
The activity of a series of imidazo[2,1-b]thiazole guanylhydrazones as inhibitors of p90 ribosomal S6 kinase 2 (RSK2) is described. It was found that a small subset of compounds show both potent inhibition of RSK2 kinase activity and tumor cell growth in vitro. Detailed study of one of the most active compounds indicates a high degree of selectivity for inhibition of RSK2 compared to a spectrum of other related kinases. Selective inhibition of the MCF-7 breast tumor cell line compared to MCF-10A non-transformed cells, as well as selective inhibition of the biomarker GSK3 provides evidence that the compounds can affect the RSK2 target in cells.
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- 2011
8. New isatin derivatives with antioxidant activity
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Massimiliano Granaiola, Emanuela Greco, Aldo Andreani, Silvia Burnelli, Alberto Leoni, Rinaldo Cervellati, Mirella Rambaldi, Alessandra Locatelli, Mauro Andrea Cremonini, Lucilla Varoli, Rita Morigi, Giuseppe Placucci, A. Andreani, S. Burnelli, M. Granaiola, A. Leoni, A. Locatelli, R. Morigi, M. Rambaldi, L. Varoli, M. A. Cremonini, G. Placucci, R. Cervellati, and E. Greco
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Isatin ,Pharmacology ,Magnetic Resonance Spectroscopy ,Antioxidant ,Bicyclic molecule ,medicine.medical_treatment ,Organic Chemistry ,Antineoplastic Agents ,General Medicine ,Chemical synthesis ,NMR ,Antioxidants ,Mass Spectrometry ,ANTITUMOR ,BRIGGS-RAUSCHER METHOD ,chemistry.chemical_compound ,chemistry ,Biochemistry ,Drug Discovery ,medicine ,Lactam ,Phenols ,ANTIOXIDANT ACTIVITY - Abstract
The reaction between isatin and 2,5-dimethoxyaniline is described. The main product was identified as 3,3-bis(4-amino-2,5-dimethoxyphenyl)-1,3-dihydroindol-2-one. The antioxidant activity of the compounds isolated was evaluated with two methods. Three published antitumor E-3-(2-chloro-3-indolylmethylene)1,3-dihydroindol-2-ones entered the same tests to search whether they are endowed with antioxidant activity too. 3,3-Bis(4-amino-2,5-dimethoxyphenyl)-1,3-dihydroindol-2-one and the three antitumor agents showed a good chemical antioxidant activity.
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- 2010
9. Diphenidol-related diamines as novel muscarinic M4 receptor antagonists
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Massimiliano Granaiola, Andrea Bedini, Lucilla Varoli, Alberto Leoni, Alessandra Locatelli, Aldo Andreani, Mirella Rambaldi, Rita Morigi, Silvia Burnelli, Santi Mario Spampinato, Nicola Fazio, L. Varoli, A. Andreani, S. Burnelli, M. Granaiola, A. Leoni, A. Locatelli, R. Morigi, M. Rambaldi, A. Bedini, N. Fazio, and S. Spampinato
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Allosteric modulator ,Stereochemistry ,medicine.medical_treatment ,Clinical Biochemistry ,Allosteric regulation ,Pharmaceutical Science ,M4-SELECTIVE MUSCARINIC ANTAGONISTS ,CHO Cells ,Muscarinic Antagonists ,Diamines ,Binding, Competitive ,Biochemistry ,ALLOSTERIC MODULATION ,Radioligand Assay ,Structure-Activity Relationship ,chemistry.chemical_compound ,Cricetulus ,MUSCARINIC RECEPTOR BINDING ASSAYS ,Allosteric Regulation ,Piperidines ,Cricetinae ,Drug Discovery ,Muscarinic acetylcholine receptor ,medicine ,Animals ,Humans ,Diphenidol ,Methiodide ,Receptor ,Molecular Biology ,FUNCTIONAL STUDIES ,Acetylcholine receptor ,Receptor, Muscarinic M4 ,Staining and Labeling ,Cell Membrane ,Organic Chemistry ,N-Methylscopolamine ,Kinetics ,DIPHENIDOL DIAMINE DERIVATIVES ,chemistry ,Competitive antagonist ,Molecular Medicine - Abstract
A series of hydrochloride derivatives 2a – 9a and quaternary ammonium derivatives 3b – 9b of diphenidol have been synthesized and characterized in receptor binding and cellular functional assays versus human muscarinic M 1 –M 5 receptors expressed in CHO cells. Compound 8b , a methiodide derivative with a bipiperidinyl moiety and a second diphenidol framework, showed a potent and selective M 4 activity as competitive antagonist. Moreover 8b , acting as an allosteric modulator, was able to retard the dissociation rate of [ 3 H]- N -methylscopolamine from CHO-M 4 cell membranes exposed to atropine. Taken together, these data suggest that 8b might open new avenues to the discovery of novel multivalent antagonists for the muscarinic receptors.
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- 2008
10. Chemiluminescent high-throughput microassay applied to imidazo[2,1-b]thiazole derivatives as potential acetylcholinesterase and butyrylcholinesterase inhibitors
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Aldo Andreani, Massimiliano Granaiola, Silvia Burnelli, Rita Morigi, Alessandra Locatelli, Massimo Guardigli, Aldo Roda, Alberto Leoni, Mirella Rambaldi, M. Rizzoli, Lucilla Varoli, A. Andreani, S. Burnelli, M. Granaiola, M. Guardigli, A. Leoni, A. Locatelli, R. Morigi, M. Rambaldi, M. Rizzoli, L. Varoli, and A. Roda
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Alkylation ,ANTIBUTYRYLCHOLINESTERASE ACTIVITY ,Acylation ,IMIDAZO[2 ,Chemical synthesis ,Inhibitory Concentration 50 ,chemistry.chemical_compound ,Drug Discovery ,Animals ,Thiazole ,Butyrylcholinesterase ,Cholinesterase ,Pharmacology ,chemistry.chemical_classification ,Binding Sites ,Dose-Response Relationship, Drug ,biology ,Organic Chemistry ,Imidazoles ,Benzene ,Biological activity ,General Medicine ,Acetylcholinesterase ,CHEMILUMINESCENCE ,Kinetics ,Thiazoles ,Enzyme ,ANTIACETYLCHOLINESTERASE ACTIVITY ,chemistry ,Biochemistry ,Enzyme inhibitor ,Drug Design ,Luminescent Measurements ,biology.protein ,Cholinesterase Inhibitors ,1-B]THIAZOLE - Abstract
The synthesis of a new series of imidazo[2,1-b]thiazole derivatives is described. They were tested as potential acetylcholinesterase and butyrylcholinesterase inhibitors by means of a chemiluminescent microassay. Although most of the new compounds did not show significant cholinesterase inhibition potency, three of them displayed selective antiacetylcholinesterase activity in the micromolar range.
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- 2008
11. Cytotoxic activities of substituted 3-(3,4,5-trimethoxybenzylidene)- 1,3-dihydroindol-2-ones and studies on their mechanisms of action
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Tam Luong Nguyen, Massimiliano Granaiola, Mirella Rambaldi, Ruoli Bai, Rita Morigi, Aldo Andreani, Lucilla Varoli, Francesco Vieceli Dalla Sega, Alessandra Locatelli, Cecilia Prata, Ernest Hamel, A. Andreani, M. Granaiola, A. Locatelli, R. Morigi, M. Rambaldi, L. Varoli, F. Vieceli Dalla Sega, C. Prata, T. L. Nguyen, R. Bai, and E. Hamel
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Drug ,Models, Molecular ,Indoles ,Cell Survival ,media_common.quotation_subject ,Antineoplastic Agents ,Antiproliferative activity ,Pharmacology ,Benzylidene Compounds ,Article ,chemistry.chemical_compound ,Structure-Activity Relationship ,Drug Discovery ,medicine ,Tumor Cells, Cultured ,Cytotoxic T cell ,Humans ,Oxindole ,Developmental Therapeutics Program ,media_common ,Cell Proliferation ,Dose-Response Relationship, Drug ,Molecular Structure ,Organic Chemistry ,NADPH oxidase 4 ,Myeloid leukemia ,NOX4 ,Cancer ,General Medicine ,medicine.disease ,chemistry ,Mechanism of action ,Knoevenagel reaction ,medicine.symptom ,Drug Screening Assays, Antitumor - Abstract
The synthesis of new trimethoxybenzylidene–indolinones is reported. Their cytotoxic activity was evaluated according to Developmental Therapeutics Program, National Cancer Institute, Bethesda, MD, drug screen protocols. The study of the mechanism of action suggests that inhibition of Nox4 in B1647 cells (acute myeloid leukemia) could contribute to the antiproliferative effect of some compounds. Moreover, inhibition of tubulin assembly was observed for the most cytotoxic compound, and the structural basis for this activity was delineated by binding models.
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- 2013
12. Substituted 3-(5-imidazo[2,1-b]thiazolylmethylene)-2-indolinones and analogues: synthesis, cytotoxic activity, and study of the mechanism of action
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Rita Morigi, Claudio Stefanelli, Tam Luong Nguyen, Giovanna Farruggia, Robert H. Shoemaker, Natalia Calonghi, Lanfranco Masotti, Ernest Hamel, Massimiliano Granaiola, Aldo Andreani, Mirella Rambaldi, Concettina Cappadone, Alessandra Locatelli, Lucilla Varoli, A. Andreani, M. Granaiola, A. Locatelli, R. Morigi, M. Rambaldi, L. Varoli, N. Calonghi, C. Cappadone, G. Farruggia, C. Stefanelli, L. Masotti, T.L. Nguyen, E. Hamel, and R.H. Shoemaker
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G2 Phase ,Models, Molecular ,Indoles ,Antineoplastic Agents ,Apoptosis ,CYTOTOXIC ACTIVITY ,COMBRETASTATIN A-4 ,Article ,TUBULIN ASSEMBLY ,chemistry.chemical_compound ,Structure-Activity Relationship ,Tubulin ,Cell Line, Tumor ,Drug Discovery ,medicine ,Cytotoxic T cell ,Humans ,Phosphorylation ,Protein kinase B ,Cell Proliferation ,Combretastatin ,IMIDAZO-THIAZOLYLMETHYLENE-2-INDOLINONES ,biology ,KINASE AKT ,Tubulin Modulators ,Chemistry ,Cell growth ,Imidazoles ,Enzyme Activation ,Thiazoles ,Mechanism of action ,Biochemistry ,Cancer cell ,biology.protein ,Molecular Medicine ,medicine.symptom ,Drug Screening Assays, Antitumor ,Mitogen-Activated Protein Kinases ,Colchicine ,Proto-Oncogene Proteins c-akt ,Cell Division ,Protein Binding ,Signal Transduction - Abstract
The synthesis of substituted 3-(5-imidazo[2,1-b]thiazolylmethylene)-2-indolinones and analogues is reported. Their cytotoxic activity was evaluated according to protocols available at the National Cancer Institute (NCI), Bethesda, MD. The action of selected compounds was examined for potential inhibition of tubulin assembly in comparison with the potent colchicine site agent combretastatin A-4. The most potent compounds also strongly and selectively inhibited the phosphorylation of the oncoprotein kinase Akt in cancer cells. The effect of the most interesting compounds was examined on the growth of HT-29 colon cancer cells. These compounds caused the cells to arrest in the G2/M phase of the cell cycle, as would be expected for inhibitors of tubulin assembly.
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- 2012
13. Diethyl 4-(6-Chloroimidazo[2,1-b]thiazol-5-yl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate and Ethyl 4-(6-Chloroimidazo[2,1-b]thiazol-5-yl)-6-methyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate
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Alberto Leoni, Alessandro Consorti, Rita Morigi, Alessandra Locatelli, Mirella Rambaldi, R. Morigi, A. Locatelli, M. Rambaldi, A. Consorti, and A. Leoni
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14-DIHYDROPIRIDINES ,IMIDAZO[21-b]THIAZOLE ,Chemistry ,Stereochemistry ,Organic Chemistry ,Biginelli reaction ,Dihydropyridine ,3,4-dihydropyrimidin-2(1H)-ones ,Biochemistry ,34-DIHYDROPYRIMIDIN-2(1H)ONES ,lcsh:QD146-197 ,imidazo[2,1-b]thiazole ,chemistry.chemical_compound ,medicine ,lcsh:Inorganic chemistry ,Carboxylate ,Physical and Theoretical Chemistry ,medicine.drug ,1,4-dihydropyridines - Abstract
Diethyl 4-(6-chloroimidazo[2,1-b]thiazol-5-yl)-2,6-dimethyl-1,4-dihydropyridine- 3,5-dicarboxylate and ethyl 4-(6-chloroimidazo[2,1-b]thiazol-5-yl)-6-methyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate were obtained simultaneously by the Biginelli reaction using a green protocol and curtailing reaction time.
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- 2012
14. Benzoindol-2-one derivatives inducing mitochondria-mediated apoptosis associated with magnesium content decrease
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LOCATELLI, ALESSANDRA, MORIGI, RITA, LEONI, ALBERTO, GRANAIOLA, MASSIMILIANO, VAROLI, LUCILLA, RAMBALDI, MIRELLA, ANDREANI, ALDO, MEROLLE, LUCIA, CAPPADONE, CONCETTINA, FARRUGGIA, GIOVANNA, A. Locatelli, R. Morigi, A. Leoni, M. Granaiola, L. Varoli, M. Rambaldi, A. Andreani, L. Merolle, C. Cappadone, and G. Farruggia
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Benzoindol-2-one ,magnesium ,apoptosi - Published
- 2012
15. SYNTHESIS OF 3-(5-IMIDAZO[2,1-b]THIAZOLYLMETHYLENE)-2-INDOLINONES INHIBITING TUBULIN ASSEMBLY AND INDUCING APOPTOSIS IN HT-29 COLON CANCER CELLS
- Author
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MORIGI, RITA, ANDREANI, ALDO, GRANAIOLA, MASSIMILIANO, LOCATELLI, ALESSANDRA, RAMBALDI, MIRELLA, VAROLI, LUCILLA, CALONGHI, NATALIA, CAPPADONE, CONCETTINA, FARRUGGIA, GIOVANNA, STEFANELLI, CLAUDIO, MASOTTI, LANFRANCO, T. L. Nguyen, E. Hamel, R. H. Shoemaker, SCI, R. Morigi, A. Andreani, M. Granaiola, A. Locatelli, M. Rambaldi, L. Varoli, N. Calonghi, C. Cappadone, G. Farruggia, C. Stefanelli, L. Masotti, T. L. Nguyen, E. Hamel, and R. H. Shoemaker
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HT-29 Colon cancer ,2-Indolinone ,Apoptosi ,Imidazo[21-b]thiazoles ,Tubulin assembly - Published
- 2012
16. Determination of octopamine and tyramine traces in dietary supplements and phytoextracts by high performance liquid chromatography after derivatization with 2,5-dimethyl-1H-pyrrole-3,4-dicarbaldehyde
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Rita Gatti, Cinzia Lotti, Rita Morigi, Aldo Andreani, R. Gatti, C. Lotti, R. Morigi, and A. Andreani
- Subjects
Citrus ,Spectrometry, Mass, Electrospray Ionization ,Electrospray ionization ,PRE-COLUMN DERIVATIZATION ,Tyramine ,Biochemistry ,High-performance liquid chromatography ,Analytical Chemistry ,chemistry.chemical_compound ,Drug Stability ,Limit of Detection ,Pyrroles ,Derivatization ,Acetonitrile ,Nuclear Magnetic Resonance, Biomolecular ,Octopamine ,Chromatography, High Pressure Liquid ,CITRUS AURANTIUM ,Detection limit ,Aldehydes ,Chromatography ,Plant Extracts ,Spectrum Analysis ,Organic Chemistry ,Reproducibility of Results ,General Medicine ,chemistry ,Reagent ,Dietary Supplements ,Proton NMR ,Linear Models ,Methanol ,HPLC - Abstract
The use of 2,5-dimethyl-1H-pyrrole-3,4-dicarbaldehyde (DPD) as a pre-column derivatization reagent for HPLC (high performance liquid chromatography) analysis of octopamine (oct) and tyramine (tyr) is proposed. The compound reacts under mild conditions (2 min at ambient temperature) with primary amino groups. The derivatization conditions were optimized by considering different parameters (temperature, time and reagent concentration). The synthesized oct and tyr adducts were characterized by 1 H NMR (nuclear magnetic resonance), ESI-MS (electrospray ionization mass spectrometry), IR (infrared) and UV (ultraviolet). Derivative chromatographic separations were performed on a Sinergy Hydro-RP column (150 mm × 4.6 mm i.d.) using a mobile phase consisting of methanol and triethylammonium phosphate buffer (pH 3; 10 mM) at varying composition gradient elution and at a flow rate of 0.8 mL/min. Detection was set at λ = 320 nm. The obtained results were compared with those achieved by a validated direct HPLC method with detection at λ = 275 nm using a Sinergy Polar-RP column (250 mm × 3 mm i.d.) by isocratic elution conditions with a mobile phase consisting of methanol/acetonitrile/sodium pentanesulphonate (SPS; pH 3; 10 mM), 7.5:7.5:85 (v/v/v) at a flow rate of 0.3 mL/min. Derivatization method sensitivity proved to be ten times higher than direct method. Limit of detection of oct and tyr was 0.010 and 0.008 μg/mL, respectively. The reliability of the pre-column method was satisfactory also in terms of linearity (from 0.028 to 1.255 and 0.024 to 1.244 μg/mL for oct and tyr, respectively), precision (relative standard deviation ≤2, without significant differences between intra-day and inter-day data) and recovery (from 98.9 to 101.2%). The proposed method showed to be suitable for a reliable determination of oct and tyr traces in commercially available phytoproducts using the instrumentation usually present in any analytical laboratory.
- Published
- 2011
17. Substituted E-3-(3-Indolylmethylene)-1,3-dihydroindol-2-ones with Antitumor Activity. In Depth Study of the Effect on Growth of Breast Cancer Cells
- Author
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Maddalena Zini, Stefania Bellini, Massimiliano Granaiola, Alberto Leoni, Natalia Calonghi, Aldo Andreani, Claudio Stefanelli, Lanfranco Masotti, Rita Morigi, Alessandra Locatelli, Silvia Burnelli, Mirella Rambaldi, Lucilla Varoli, Robert H. Shoemaker, Concettina Cappadone, A. Andreani, S. Bellini, S. Burnelli, M. Granaiola, A. Leoni, A. Locatelli, R. Morigi, M. Rambaldi, L. Varoli, N. Calonghi, C. Cappadone, M. Zini, C. Stefanelli, L. Masotti, R.H. Shoemaker, and ITALIAN CHEMICAL SOCIETY DIVISION OF MEDICINAL CHEMISTRY
- Subjects
Cyclin-Dependent Kinase Inhibitor p21 ,Indoles ,Cell ,Antineoplastic Agents ,Apoptosis ,Breast Neoplasms ,Pharmacology ,ANTITUMORALI ,Article ,INDOLINONI ,Structure-Activity Relationship ,Bcl-2-associated X protein ,Breast cancer ,Drug Discovery ,medicine ,Humans ,Cytotoxicity ,Cell Proliferation ,bcl-2-Associated X Protein ,P53 ,INDOLI ,biology ,Cell growth ,Chemistry ,Cytotoxins ,Cell Cycle ,CASPASI ,Cancer ,Stereoisomerism ,HOLLOW FIBER ,CICLO CELLULARE ,Cell cycle ,medicine.disease ,Cytostatic Agents ,medicine.anatomical_structure ,REAZIONE DI KNOEVENAGEL ,biology.protein ,Molecular Medicine ,Female ,Drug Screening Assays, Antitumor ,Tumor Suppressor Protein p53 - Abstract
The synthesis of new substituted E-3-(3-indolylmethylene)1,3-dihydroindol-2-ones is reported. The antitumor activity was evaluated according to protocols available at the National Cancer Institute (NCI), Bethesda, MD. Structure-activity relationships are discussed. The action of selected compounds was investigated in MCF-7 breast cancer cells. The ability of these derivatives to inhibit cellular proliferation was accompanied by increased level of p53 and its transcriptional targets p21 and Bax, interference in the cell cycle progression with cell accumulation in the G2/M phase, and lastly activation of apoptosis.
- Published
- 2010
18. Bis-guanylhydrazone diimidazo[1,2-a:1,2-c]pyrimidine as a novel and specific G-quadruplex binding motif
- Author
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Rita Morigi, Stefania Bellini, Shozeb Haider, Aldo Andreani, Silvia Burnelli, Lucilla Varoli, Alberto Leoni, Massimiliano Granaiola, Silvia Sparapani, Stephen Neidle, Mekala Gunaratnam, Mirella Rambaldi, Alessandra Locatelli, S. Sparapani, S. Bellini, M. Gunaratnam, S.M. Haider, A. Andreani, M. Rambaldi, A. Locatelli, R. Morigi, M. Granaiola, L. Varoli, S. Burnelli, A. Leoni, and S. Neidle
- Subjects
Models, Molecular ,Dna duplex ,Mitoguazone ,Pyrimidine ,Molecular model ,Stereochemistry ,G-quadruplex ,Catalysis ,chemistry.chemical_compound ,ATTIVITÀ ANTIPROLIFERATIVA ,Materials Chemistry ,Fluorescence Resonance Energy Transfer ,heterocyclic compounds ,Computer Simulation ,G-QUADRUPLEX ,G quadruplex binding ,DIIMIDAZO-PIRIMIDINE ,Chemistry ,Metals and Alloys ,General Chemistry ,DNA ,Small molecule ,Surfaces, Coatings and Films ,Electronic, Optical and Magnetic Materials ,G-Quadruplexes ,Förster resonance energy transfer ,Pyrimidines ,Biochemistry ,Ceramics and Composites ,FRET ,BIS-GUANILIDRAZONI - Abstract
A bis-guanylhydrazone derivative of diimidazo[1,2-a:1,2-c]pyrimidine has unexpectedly been found to be a potent stabiliser of several quadruplex DNAs, whereas there is no significant interaction with duplex DNA. Molecular modeling suggests that the guanylhydrazone groups play an active role in quadruplex binding.
- Published
- 2010
19. Antitumor activity of imidazo[2,1-b]thiazole guanylhydrazones and analogs
- Author
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RAMBALDI, MIRELLA, ANDREANI, ALDO, BURNELLI, SILVIA, GRANAIOLA, MASSIMILIANO, LEONI, ALBERTO, LOCATELLI, ALESSANDRA, MORIGI, RITA, VAROLI, LUCILLA, M. Rambaldi, A. Andreani, S. Burnelli, M. Granaiola, A. Leoni, A. Locatelli, R. Morigi, and L. Varoli
- Subjects
ANTITUMORALE ,GUANILIDRAZONI ,IMIDAZOTIAZOLI ,NCI - Published
- 2009
20. Antitumor Activity of Bis-Indole Derivatives
- Author
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Massimiliano Granaiola, Rita Morigi, Carole Grasso, Angelika Burger, Mirella Rambaldi, Aldo Andreani, Alberto Leoni, Gerhard Kelter, Silvia Burnelli, Laura Landi, Lucilla Varoli, Heinz-Herbert Fiebig, Alessandra Locatelli, Cecilia Prata, Michael V. Berridge, Mark W. Kunkel, A. Andreani, S. Burnelli, M. Granaiola, A. Leoni, A. Locatelli, R. Morigi, M. Rambaldi, L. Varoli, L. Landi, C. Prata, M. V. Berridge, C. Grasso, H-H. Fiebig, G. Kelter, A. M. Burger, and M. W. Kunkel
- Subjects
PMET ,Indoles ,Stereochemistry ,Ubiquitin-Protein Ligases ,Antineoplastic Agents ,ANTITUMORALI ,Chemical synthesis ,Article ,chemistry.chemical_compound ,INIBIZIONE ,Cell Line, Tumor ,Neoplasms ,Drug Discovery ,Pyridine ,medicine ,Moiety ,COMPARE ,Animals ,Cell Proliferation ,Indole test ,INDOLI ,Molecular Structure ,Chemistry ,In vitro ,Piperazine ,Mechanism of action ,Lactam ,Molecular Medicine ,medicine.symptom - Abstract
This paper reports the synthesis of compounds formed by two indole systems separated by a heterocycle (pyridine or piperazine). As a primary screening, the new compounds were submitted to the National Cancer Institute for evaluation of antitumor activity in the human cell line screen. The pyridine derivatives were far more active than the piperazine derivatives. For the study of the mechanism of action, the most active compounds were subjected to COMPARE analysis and to further biological tests including proteasome inhibition and inhibition of plasma membrane electron transport. The compound bearing the 5-methoxy-2-indolinone moiety was subjected to the first in vivo experiment (hollow fiber assay) and was active. It was therefore selected for the second in vivo experiment (human tumor xenograft in mice). In conclusion we demonstrated that this approach was successful, since some of the compounds described are much more active than the numerous, so far prepared and tested 3-indolylmethylene-2-indolinones.
- Published
- 2008
21. New Antitumor Imidazo[2,1-b]thiazole Guanylhydrazones and Analogues
- Author
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Aldo, Andreani, Silvia, Burnelli, Massimiliano, Granaiola, Alberto, Leoni, Alessandra, Locatelli, Rita, Morigi, Mirella, Rambaldi, Lucilla, Varoli, Natalia, Calonghi, Concettina, Cappadone, Giovanna, Farruggia, Maddalena, Zini, Claudio, Stefanelli, Lanfranco, Masotti, Norman S, Radin, Robert H, Shoemaker, A. Andreani, S. Burnelli, M. Granaiola, A. Leoni, A. Locatelli, R. Morigi, M. Rambaldi, L. Varoli, N. Calonghi, C. Cappadone, G. Farruggia, M. Zini, C. Stefanelli, L. Masotti, N.S. Radin, and R.H. Shoemaker
- Subjects
Membrane Potential, Mitochondrial ,Cell Survival ,Hydrazones ,Imidazoles ,Antineoplastic Agents ,ANTITUMOR ACTIVITY ,APOPTOSIS ,IMIDAZOTHIAZOLE ,Structure-Activity Relationship ,Thiazoles ,GUANYLHYDRAZONES ,MITOCHONDRIA ,Cell Line, Tumor ,Humans ,Drug Screening Assays, Antitumor - Abstract
The synthesis of new antitumor 6-substituted imidazothiazole guanylhydrazones is described. Moreover, a series of compounds with a different basic chain at the 5 position were prepared. Finally, the replacement of the thiazole ring in the imidazothiazole system was also considered. All the new compounds prepared were submitted to the NCI cell line screen for evaluation of their antitumor activity. A few selected compounds were submitted to additional biological studies concerning effects on the cell cycle, apoptosis, and mitochondria.
- Published
- 2008
22. Substituted (E)-3-(2-chloro-3-indolylmethylene)-1,3-dihydroindol-2-ones as antitumor agents: SARs and study of the mechanism of action
- Author
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MORIGI, RITA, ANDREANI, ALDO, BURNELLI, SILVIA, GRANAIOLA, MASSIMILIANO, LEONI, ALBERTO, LOCATELLI, ALESSANDRA, RAMBALDI, MIRELLA, VAROLI, LUCILLA, CALONGHI, NATALIA, CAPPADONE, CONCETTINA, FARRUGGIA, GIOVANNA, ZINI, MADDALENA, STEFANELLI, CLAUDIO, MASOTTI, LANFRANCO, AMERICAN CHEMICAL SOCIETY, DIVISION OF MEDICINAL CHEMISTRY, R. Morigi, A. Andreani, S. Burnelli, M. Granaiola, A. Leoni, A. Locatelli, M. Rambaldi, L. Varoli, N. Calonghi, C. Cappadone, G. Farruggia, M. Zini, C. Stefanelli, and L. Masotti.
- Subjects
ANTITUMOR ,2-INDOLINONE ,CASPASE ,KNOEVENAGEL ,APOPTOSIS - Published
- 2007
23. Il Colle di Barikot
- Author
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Colliva L, CALLIERI P, COLLIVA L, GALLI M, MICHELI R, MORIGI E, OLIVIERI L M, and Colliva L
- Subjects
Archaeology ,Excavations ,Swat ,Pakistan ,Barikot - Abstract
As from 1998 investigation at Barikot was extended to the hill, with its crescent moon shape protectively rising above the area of the ancient city, constituting natural defence on the north side. The earliest material dates back to the 2nd millennium B.C., although the earliest conserved structures belong to the 1st-2nd century A.D. Evidence suggesting that the two natural terraces on the hilltop constituted the Acropolis of the Indo-Greek city can be seen in the traces of a sturdy masonry structure that was plundered for material to build the subsequent structures, and that probably corresponds with a stretch of the city wall. The most spectacular utilisation was achieved around the 7th century AD when the eastern terrace was extended with a tall and solid substruction wall for the construction of a monumental sacred complex that dominated the valley.
- Published
- 2006
24. Synthesis and antitumor activity of Guanylhydrazones from 6-(2,4-dichloro-5-nitrophenyl)imidazo[2,1-b]thiazoles and 6-pyridylimidazo[2,1-b]thiazoles
- Author
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Claudio Stefanelli, Aldo Andreani, Alberto Leoni, Giovanna Farruggia, Mirella Rambaldi, Silvia Burnelli, Mark W. Kunkel, Lanfranco Masotti, Lucilla Varoli, Alessandra Locatelli, Rita Morigi, Massimiliano Granaiola, A. Andreani, S. Burnelli, M. Granaiola, A. Leoni, A. Locatelli, R. Morigi, M. Rambaldi, L. Varoli, G. Farruggia, C. Stefanelli, L. Masotti, and M.W. Kunkel
- Subjects
chemistry.chemical_classification ,Antitumor activity ,Imidazothiazole ,Stereochemistry ,Nitro compound ,Chemical synthesis ,In vitro ,chemistry.chemical_compound ,Carbon-Carbon Lyases ,Enzyme ,GUANYLHYDRAZONES ,IMIDAZOTHIAZOLES ,chemistry ,Mechanism of action ,Drug Discovery ,medicine ,Molecular Medicine ,ANTICANCER ,medicine.symptom - Abstract
The design and synthesis of antitumor imidazothiazole guanylhydrazones are reported. The compounds were submitted to NCI for testing. All but one were more active than methyl-GAG. A few compounds were selected for further studies in search of a possible mechanism of action. The results from these studies and a final search with the NCI COMPARE algorithm suggest that the guanylhydrazones described in this paper are acting through a novel mechanism of action.
- Published
- 2006
25. Antitumor Activity of Substituted E-3-(3,4,5-Trimethoxybenzylidene)-1,3-dihydroindol-2-ones
- Author
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Alessandra Locatelli, Silvia Burnelli, Alberto Leoni, Massimiliano Granaiola, Mark W. Kunkel, Aldo Andreani, Mirella Rambaldi, Lucilla Varoli, Rita Morigi, A. Andreani, S. Burnelli, M. Granaiola, A. Leoni, A. Locatelli, R. Morigi, M. Rambaldi, L. Varoli, and M.W. Kunkel
- Subjects
Antitumor activity ,INDOLI ,Chemistry ,Stereochemistry ,ANTITUMORALI ,Chemical synthesis ,In vitro ,chemistry.chemical_compound ,Active compound ,Drug Discovery ,COMBRETASTATINA ,Lactam ,Molecular Medicine ,COMPARE ,Cytotoxicity ,Derivative (chemistry) ,Biological evaluation - Abstract
The design and synthesis of anticancer E-3-(3,4,5-trimethoxybenzylidene)-1,3-dihydroindol-2-ones is reported. Strong COMPARE correlations among the cell line responses suggest that these compounds may be acting similarly through a combination of different mechanisms of action. The 5-methoxy derivative (2h) was the most active compound with a mean pGI50 of 6.34, and it is now under review by Biological Evaluation Committee of the National Cancer Institute for possible further studies.
- Published
- 2006
26. New substituted E-3-(2-Chloro-3-indolylmethylene)1,3-dihydroindol-2-ones with antitumor activity
- Author
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ANDREANI, ALDO, BURNELLI, SILVIA, GRANAIOLA, MASSIMILIANO, LEONI, ALBERTO, LOCATELLI, ALESSANDRA, MORIGI, RITA, RAMBALDI, MIRELLA, VAROLI, LUCILLA, FARRUGGIA, GIOVANNA, CALONGHI, NATALIA, STEFANELLI, CLAUDIO, MASOTTI, LANFRANCO, M. W. Kunkel, A. Andreani, S. Burnelli, M. Granaiola, A. Leoni, A. Locatelli, R. Morigi, M. Rambaldi, L. Varoli, G. Farruggia, N. Calonghi, C. Stefanelli, L. Masotti, and M.W. Kunkel
- Published
- 2006
27. Synthesis and chemiluminescent high throughput microassay for inhibition of acetylcholinesterase and butyrylcholinesterase activity by imidazo[2,1-b]thiazole derivatives
- Author
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ANDREANI, ALDO, BURNELLI, SILVIA, GRANAIOLA, MASSIMILIANO, GUARDIGLI, MASSIMO, LEONI, ALBERTO, LOCATELLI, ALESSANDRA, MORIGI, RITA, RAMBALDI, MIRELLA, RODA, ALDO, VAROLI, LUCILLA, A. Andreani, S. Burnelli, M.Granaiola, M. Guardigli, A. Leoni, A. Locatelli, R. Morigi, M. Rambaldi, A. Roda, and L. Varoli
- Published
- 2006
28. Synthesis and antitumor activity of guanylhydrazones from 6-(2,4-dichloro-5-nitrophenyl)- and 6-pyridyl-imidazo[2,1-b]thiazoles
- Author
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ANDREANI, ALDO, GRANAIOLA, MASSIMILIANO, LEONI, ALBERTO, LOCATELLI, ALESSANDRA, MORIGI, RITA, RAMBALDI, MIRELLA, STEFANELLI, CLAUDIO, FARRUGGIA, GIOVANNA, MASOTTI, LANFRANCO, COMITATO SCIENTIFICO, A. Andreani, M. Granaiola, A. Leoni, A. Locatelli, R. Morigi, M. Rambaldi, C. Stefanelli, G. Farruggia, and L. Masotti
- Published
- 2005
29. Potential Antitumor Agents. 37. Synthesis and Antitumor Activity of Guanylhydrazones from Imidazo[2,1-b]thiazoles and from the New Heterocyclic System Thiazolo[2',3':2,3]imidazo[4,5-c]quinoline
- Author
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Massimiliano Granaiola, Christian Bergamini, Giorgio Lenaz, Giovanna Farruggia, Aldo Andreani, Mirella Rambaldi, Romana Fato, Alessandra Locatelli, Alberto Leoni, Rita Morigi, A. Andreani, M. Granaiola, A. Leoni, A. Locatelli, R. Morigi, M. Rambaldi, G. Lenaz, R. Fato, C. Bergamini, and G. Farruggia
- Subjects
Cell Survival ,HL60 ,Stereochemistry ,Nitro compound ,Antineoplastic Agents ,Mitochondria, Liver ,In Vitro Techniques ,Chemical synthesis ,Membrane Potentials ,Structure-Activity Relationship ,chemistry.chemical_compound ,Oxygen Consumption ,Cell Line, Tumor ,Drug Discovery ,Animals ,Humans ,Structure–activity relationship ,Cytotoxicity ,Cell Proliferation ,chemistry.chemical_classification ,Bicyclic molecule ,Quinoline ,Hydrazones ,Imidazoles ,Rats ,Thiazoles ,Mitochondrial respiratory chain ,chemistry ,Quinolines ,Molecular Medicine ,Drug Screening Assays, Antitumor - Abstract
This paper reports synthesis and antitumor activity of new guanylhydrazones from imidazo[2,1-b]thiazoles and from the new heterocyclic system thiazolo[2',3':2,3]imidazo[4,5-c]quinoline. The compounds were tested as potential antitumor agents at the National Cancer Institute. The effect of the guanylhydrazone of 2-chloro-6-(2,5-dimethoxy-4-nitrophenyl)imidazo[2,1-b]- thiazole-5-carbaldehyde (41) was investigated, and it was found to be an inhibitor of Complex III of the mitochondrial respiratory chain and is able to induce apoptosis in the cell lines HT29 and HL60.
- Published
- 2005
30. Sintesi e attività antitumorale di guanilidrazoni derivati dal nucleo imidazo[2,1-b]tiazolico e dal nuovo sistema eterociclico tiazolo[2',3':2,3]imidazo[4,5-c]chinolina
- Author
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ANDREANI, ALDO, GRANAIOLA, MASSIMILIANO, LEONI, ALBERTO, LOCATELLI, ALESSANDRA, MORIGI, RITA, RAMBALDI, MIRELLA, LENAZ, GIORGIO, FATO, ROMANA, BERGAMINI, CHRISTIAN, FARRUGGIA, GIOVANNA, COMITATO SCIENTIFICO, A. Andreani, M. Granaiola, A. Leoni, A. Locatelli, R. Morigi, M. Rambaldi, G. Lenaz, R. Fato, C. Bergamini, and G. Farruggia
- Published
- 2004
31. Antitumor activity of compounds bearing the new heterocyclic system thiazolo[2',3':2,3]imidazo[4,5-c]quinoline
- Author
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MORIGI, RITA, ANDREANI, ALDO, GRANAIOLA, MASSIMILIANO, LEONI, ALBERTO, LOCATELLI, ALESSANDRA, RAMBALDI, MIRELLA, COMITATO SCIENTIFICO, R. Morigi, A. Andreani, M. Granaiola, A. Leoni, A. Locatelli, and M. Rambaldi
- Published
- 2004
32. N-Benzyl-2-chloroindole-3-carboxylic acids as potential anti-inflammatory agents. Synthesis and screening for the effects on human neutrophil functions and on COX1/COX2 activity
- Author
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Rita Morigi, Aldo Roda, Massimo Guardigli, Alberto Leoni, Aldo Andreani, Alessandra Locatelli, Serena Traniello, Massimiliano Granaiola, Susanna Spisani, Mirella Rambaldi, A. Andreani, M. Granaiola, A. Leoni, A. Locatelli, R. Morigi, M. Rambaldi, A. Roda, M. Guardigli, S. Traniello, and S. Spisani
- Subjects
Indoles ,Human neutrophil ,Neutrophils ,medicine.drug_class ,Carboxylic acid ,Carboxylic Acids ,Drug Evaluation, Preclinical ,macromolecular substances ,Chemical synthesis ,Anti-inflammatory ,NO ,Structure-Activity Relationship ,Drug Discovery ,medicine ,Humans ,Structure–activity relationship ,Pharmacology ,chemistry.chemical_classification ,Indole test ,indole ,inflammation ,neutrophil ,COX1/COX2 ,Molecular Structure ,biology ,Chemistry ,Anti-Inflammatory Agents, Non-Steroidal ,Organic Chemistry ,Membrane Proteins ,General Medicine ,In vitro ,Enzyme Activation ,Enzyme ,Biochemistry ,Cyclooxygenase 2 ,Prostaglandin-Endoperoxide Synthases ,Enzyme inhibitor ,Drug Design ,Cyclooxygenase 1 ,biology.protein - Abstract
The synthesis of N-benzyl-2-chloroindole-3-carboxylic acids related to indomethacin is reported. These compounds were tested on in vitro human neutrophil activation. Some of them, more soluble in water, were tested to define the influence on prostaglandin biosynthesis via inhibition of cyclooxygenases (COX1 and COX2) by a chemiluminescent method suitable for fast screening. Several derivatives showed inhibitory effects and in some cases were more active than the parent compound.
- Published
- 2004
33. Sintesi di derivati imidazo[2,1-b]tiazolici e valutazioone dell'attività inibitoria dell'acetilcolinesterasi mediante un metodo HTS chemiluminescente
- Author
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ANDREANI, ALDO, GRANAIOLA, MASSIMILIANO, GUARDIGLI, MASSIMO, LEONI, ALBERTO, LOCATELLI, ALESSANDRA, MORIGI, RITA, RAMBALDI, MIRELLA, RODA, ALDO, COMITATO SCIENTIFICO, A. Andreani, M. Granaiola, M. Guardigli, A. Leoni, A. Locatelli, R. Morigi, M. Rambaldi, and A. Roda
- Published
- 2004
34. Attività antitumorale di nuovi 3-(5-imidazo[2,1-b]tiazolilmetilen)-2-indolinoni sostituiti e studio del loro effetto sul ciclo cellulare
- Author
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ANDREANI, ALDO, GRANAIOLA, MASSIMILIANO, LEONI, ALBERTO, LOCATELLI, ALESSANDRA, MORIGI, RITA, RAMBALDI, MIRELLA, FARRUGGIA, GIOVANNA, PAGNOTTA, ELEONORA, MASOTTI, LANFRANCO, COMITATO SCIENTIFICO, A. Andreani, M. Granaiola, A. Leoni, A. Locatelli, R. Morigi, M. Rambaldi, G. Farruggia, E. Pagnotta, and L. Masotti
- Published
- 2004
35. Identification of a new bisindolinone arresting IGROV1 cells proliferation.
- Author
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Morigi R, Zalambani C, Farruggia G, Verardi L, Esposito D, Leoni A, Borsetti F, Voltattorni M, Zambonin L, Pincigher L, Calonghi N, and Locatelli A
- Subjects
- Humans, Structure-Activity Relationship, Drug Screening Assays, Antitumor, Molecular Structure, Dose-Response Relationship, Drug, Cell Line, Tumor, Cell Movement drug effects, Indoles pharmacology, Indoles chemistry, DNA Damage, Cell Proliferation drug effects, Antineoplastic Agents pharmacology, Antineoplastic Agents chemistry, Antineoplastic Agents chemical synthesis
- Abstract
In an initial screening, a series of novel Knoevenagel adducts were submitted to the National Cancer Institute for evaluation of antitumor activity in human cell lines. In particular, compound 5f showed remarkable selectivity against IGROV1, an ovarian cancer cell line, without affecting healthy human fibroblast cells. Analyses of cytotoxicity, cell proliferation, cell migration, epigenetic changes, gene expression, and DNA damage were performed to obtain detailed information about its antitumor properties. Our results show that 5f causes proliferation arrest, decrease in motility, histone hyperacetylation, downregulation of cyclin D1 and α5 subunit of integrin β1 gene transcription. In addition, 5f treatment reduces transcript and protein levels of cyclin D1, which increases sensitivity to ionizing radiation and results in DNA damage comparable to cyclin D1 gene silencing., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)
- Published
- 2024
- Full Text
- View/download PDF
36. Balancing Affinity, Selectivity, and Cytotoxicity of Hydrazone-Based G-Quadruplex Ligands for Activation of Interferon β Genes in Cancer Cells.
- Author
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Marzano S, Miglietta G, Morigi R, Marinello J, Arleo A, Procacci M, Locatelli A, Leoni A, Pagano B, Randazzo A, Amato J, and Capranico G
- Subjects
- Genomic Instability, Humans, Hydrazones pharmacology, Interferon-beta genetics, Ligands, Antineoplastic Agents pharmacology, Cytostatic Agents, G-Quadruplexes, Neoplasms genetics
- Abstract
G-quadruplex (G4) ligands are investigated to discover new anticancer drugs with increased cell-killing potency. These ligands can induce genome instability and activate innate immune genes at non-cytotoxic doses, opening the discovery of cytostatic immune-stimulating ligands. However, the interplay of G4 affinity/selectivity with cytotoxicity and immune gene activation is not well-understood. We investigated a series of closely related hydrazone derivatives to define the molecular bases of immune-stimulation activity. Although they are closely related to each other, such derivatives differ in G4 affinity, cytotoxicity, genome instability, and immune gene activation. Our findings show that G4 affinity of ligands is a critical feature for immune gene activation, whereas a high cytotoxic potency interferes with it. The balance of G4 stabilization versus cytotoxicity can determine the level of immune gene activation in cancer cells. Thus, we propose a new rationale based on low cell-killing potency and high immune stimulation to discover effective anticancer G4 ligands.
- Published
- 2022
- Full Text
- View/download PDF
37. Isatin Bis-Indole and Bis-Imidazothiazole Hybrids: Synthesis and Antimicrobial Activity.
- Author
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Bonvicini F, Locatelli A, Morigi R, Leoni A, and Gentilomi GA
- Subjects
- Anti-Bacterial Agents pharmacology, Candida albicans, Escherichia coli, Humans, Indoles pharmacology, Microbial Sensitivity Tests, Staphylococcus aureus, Structure-Activity Relationship, Anti-Infective Agents pharmacology, Isatin pharmacology
- Abstract
Isatin and its derivatives are important heterocycles found in nature and present in numerous bioactive compounds which possess various biological activities. Moreover, it is an essential building block in organic synthesis. The discovery of novel compounds active against human pathogenic bacteria and fungi is an urgent need, and the isatin may represent the suitable scaffold in the design of biologically relevant antimicrobials. A small library of 18 isatin hybrids was synthetized and evaluated for their antimicrobial potential on three reference strains: S. aureus , E. coli , both important human pathogens infamous for causing community- and hospital-acquired severe systemic infections; and C. albicans , responsible for devastating invasive infections, mainly in immunocompromised individuals. The study highlighted two lead compounds, 6k and 6m, endowed with inhibitory activity against S. aureus at very low concentrations (39.12 and 24.83 µg/mL, respectively).
- Published
- 2022
- Full Text
- View/download PDF
38. Synthesis, in vitro cytotoxicity, molecular docking and ADME study of some indolin-2-one linked 1,2,3-triazole derivatives.
- Author
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Das A, Greco G, Kumar S, Catanzaro E, Morigi R, Locatelli A, Schols D, Alici H, Tahtaci H, Ravindran F, Fimognari C, and Karki SS
- Subjects
- Apoptosis, Cell Line, Tumor, Cell Proliferation, Drug Screening Assays, Antitumor, Humans, Indoles, Molecular Docking Simulation, Molecular Structure, Structure-Activity Relationship, Triazoles chemistry, Triazoles pharmacology, Antineoplastic Agents chemistry, Protein Kinase Inhibitors chemistry
- Abstract
In pursuit of an anticancer lead, a library of 1,2,3-triazole derivatives (7a-x) was prepared, characterized and screened for in vitro cytotoxicity in different cell lines. Most of the compounds proved to be cytotoxic with IC
50 values in the low micromolar range. Further studies showed that the most active compound 7c induces caspase-dependent apoptosis in Jurkat cells by activating both the intrinsic and the extrinsic apoptotic pathways and perturbs cell-cycle progression. Moreover, 7c did not show any genotoxic activity. Molecular docking simulations were performed against epidermal growth factor receptor (EGFR). Docking experiments showed that, compounds 7c, 7o and 7 v bind within active sites of epidermal growth factor receptor EGFR (Pdb ID: 6P8Q) by strong hydrogen bonds with residue MET793, Pi-Sulfur with residue MET790 and Pi-Alkyl type interactions with residues LEU788, ALA743. The SwissADME webserver investigation suggested that most of the synthesized compounds follow the rules of drug-likeness., (Copyright © 2022 Elsevier Ltd. All rights reserved.)- Published
- 2022
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39. Synthesis and Biological Evaluation of New Bis-Indolinone Derivatives Endowed with Cytotoxic Activity.
- Author
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Morigi R, Catanzaro E, Locatelli A, Calcabrini C, Pellicioni V, Leoni A, and Fimognari C
- Subjects
- Apoptosis drug effects, Cell Cycle drug effects, Cell Death drug effects, Cell Line, Tumor, DNA Damage drug effects, Dose-Response Relationship, Drug, Drug Screening Assays, Antitumor methods, Humans, Jurkat Cells, Molecular Structure, Oxidative Stress drug effects, Antineoplastic Agents pharmacology, Cell Proliferation drug effects, Oxindoles pharmacology
- Abstract
A series of new Knoevenagel adducts, bearing two indolinone systems, has been synthesized and evaluated on 60 human cancer cell lines according to protocols available at the National Cancer Institute (Bethesda, MD, USA). Some derivatives proved to be potent antiproliferative agents, showing GI
50 values in the submicromolar range. Compound 5b emerged as the most active and was further studied in Jurkat cells in order to determine the effects on cell-cycle phases and the kind of cell death induced. Finally, oxidative stress and DNA damage induced by compound 5b were also analyzed.- Published
- 2021
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40. Synthesis and biological evaluation of thiazole derivatives on basic defects underlying cystic fibrosis.
- Author
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Pesce E, Pedemonte N, Leoni A, Locatelli A, and Morigi R
- Subjects
- Cystic Fibrosis genetics, Cystic Fibrosis metabolism, Cystic Fibrosis Transmembrane Conductance Regulator genetics, Dose-Response Relationship, Drug, Humans, Molecular Structure, Structure-Activity Relationship, Thiazoles chemical synthesis, Thiazoles chemistry, Cystic Fibrosis drug therapy, Cystic Fibrosis Transmembrane Conductance Regulator metabolism, Thiazoles pharmacology
- Abstract
Cystic fibrosis is a genetic disease caused by loss-of-function mutations in the cystic fibrosis transmembrane conductance regulator gene, encoding for CFTR protein. The most frequent mutation is the deletion of phenylalanine at position 508 (F508del), which leads to distinct defects in channel gating and cellular processing. In last years, several thiazole containing small molecules, endowed with dual F508del-CFTR modulator activity, proved to be able to target these defects. In search of new chemical entities able to restore CFTR function, we designed and synthesized a small series of sixteen thiazole derivatives. The designed compounds were studied as correctors and potentiators of F508del-CFTR. Although none of the molecules showed significant corrector activity, compounds 10 and 11 exhibited potentiator effects, thus allowing to determine some basic structural features which enable to obtain F508del-CFTR potentiator activity. In silico ADME studies showed that these derivatives obey Lipinski's rule of five and are expected to be orally bioavailable. Therefore, these molecules may represent a good starting point for the design of analogues endowed with improved CFTR potentiator activity and a good pharmacokinetic profile., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)
- Published
- 2020
- Full Text
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41. Indole Derivative Interacts with Estrogen Receptor Beta and Inhibits Human Ovarian Cancer Cell Growth.
- Author
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Verardi L, Fiori J, Andrisano V, Locatelli A, Morigi R, Naldi M, Bertucci C, Strocchi E, Boga C, Micheletti G, and Calonghi N
- Subjects
- Cell Line, Tumor, Cell Proliferation drug effects, Female, Humans, Ovarian Neoplasms drug therapy, Ovarian Neoplasms pathology, Estrogen Receptor beta agonists, Estrogen Receptor beta chemistry, Estrogen Receptor beta metabolism, Gene Expression Regulation, Neoplastic drug effects, Indoles chemistry, Indoles pharmacology, Molecular Docking Simulation, Neoplasm Proteins agonists, Neoplasm Proteins chemistry, Neoplasm Proteins metabolism, Ovarian Neoplasms metabolism
- Abstract
Ovarian cancer remains the leading cause of mortality among gynecological tumors. Estrogen receptor beta (ERβ) expression has been suggested to act as a tumor suppressor in epithelial ovarian cancer by reducing both tumor growth and metastasis. ERβ expression abnormalities represent a critical step in the development and progression of ovarian cancer: for these reasons, its re-expression by genetic engineering, as well as the use of targeted ERβ therapies, still constitute an important therapeutic approach. 3-{[2-chloro-1-(4-chlorobenzyl)-5-methoxy-6-methyl-1 H -indol-3-yl]methylene}-5-hydroxy-6-methyl-1,3-dihydro-2 H -indol-2-one, referred to here as compound 3 , has been shown to have cytostatic as well cytotoxic effects on various hormone-dependent cancer cell lines. However, the mechanism of its anti-carcinogenic activity is not well understood. Here, we offer a possible explanation of such an effect in the human ovarian cancer cell line IGROV1. Chromatin binding protein assay and liquid chromatography mass spectrometry were exploited to localize and quantify compound 3 in cells. Molecular docking was used to prove compound 3 binding to ERβ. Mass spectrometry-based approaches were used to analyze histone post-translational modifications. Finally, gene expression analyses revealed a set of genes regulated by the ERβ/3 complex, namely CCND1, MYC, CDKN2A, and ESR2, providing possible molecular mechanisms that underline the observed antiproliferative effects.
- Published
- 2020
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- View/download PDF
42. Monohydrazone Based G-Quadruplex Selective Ligands Induce DNA Damage and Genome Instability in Human Cancer Cells.
- Author
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Amato J, Miglietta G, Morigi R, Iaccarino N, Locatelli A, Leoni A, Novellino E, Pagano B, Capranico G, and Randazzo A
- Subjects
- Antineoplastic Agents chemical synthesis, Antineoplastic Agents metabolism, Cell Line, Tumor, DNA genetics, DNA metabolism, Drug Screening Assays, Antitumor, Genome drug effects, Humans, Hydrazones chemical synthesis, Hydrazones metabolism, Ligands, R-Loop Structures drug effects, Antineoplastic Agents pharmacology, DNA drug effects, DNA Damage drug effects, G-Quadruplexes drug effects, Genomic Instability drug effects, Hydrazones pharmacology
- Abstract
Targeting G-quadruplex structures is currently viewed as a promising anticancer strategy. Searching for potent and selective G-quadruplex binders, here we describe a small series of new monohydrazone derivatives designed as analogues of a lead which was proved to stabilize G-quadruplex structures and increase R loop levels in human cancer cells. To investigate the G-quadruplex binding properties of the new molecules, in vitro biophysical studies were performed employing both telomeric and oncogene promoter G-quadruplex-forming sequences. The obtained results allowed the identification of a highly selective G-quadruplex ligand that, when studied in human cancer cells, proved to be able to stabilize both G-quadruplexes and R loops and showed a potent cell killing activity associated with the formation of micronuclei, a clear sign of genome instability.
- Published
- 2020
- Full Text
- View/download PDF
43. Synthesis of 3-(Imidazo[2,1- b ]thiazol-6-yl)-2H-chromen-2-one Derivatives and Study of Their Antiviral Activity against Parvovirus B19.
- Author
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Conti I, Morigi R, Locatelli A, Rambaldi M, Bua G, Gallinella G, and Leoni A
- Subjects
- Antiviral Agents chemistry, Antiviral Agents pharmacology, Benzopyrans chemistry, Benzopyrans pharmacology, Cell Proliferation drug effects, Cell Survival drug effects, Cells, Cultured, Humans, Molecular Structure, Parvoviridae Infections, Parvovirus B19, Human drug effects, Structure-Activity Relationship, Virus Replication drug effects, Antiviral Agents chemical synthesis, Benzopyrans chemical synthesis, Coumarins chemistry, Parvovirus B19, Human physiology
- Abstract
Parvovirus B19 (B19V) is a human pathogenic virus associated with a wide range of clinical conditions. Currently, there are no recognized antiviral drugs for B19V treatment; therefore, efforts in the search for compounds inhibiting B19V replication are now being pursued. Coumarins (chromen-2-ones) are considered a privileged structure for designing novel orally bioavailable and non-peptidic antiviral agents. To further contribute to the development of new drugs against B19V, our research was focused on the synthesis, characterization and evaluation of antiviral activity of some new 3-(imidazo[2,1- b ]thiazol-6-yl)-2H-chromen-2-one derivatives. The effects of the synthesized compounds on cell viability and viral replication were investigated by employing two relevant cellular systems, the myeloblastoid cell line UT7/EpoS1 and primary erythroid progenitor cells (EPCs). Some of the tested compounds showed inhibitory activity both on cell viability and on viral replication, depending on the cellular system. These results suggest that the mechanism involved in biological activity is sensitive to small structural changes and that it is possible to direct the activity of the 3-(imidazo[2,1- b ]thiazol-6-yl)-2H-chromen-2-one core.
- Published
- 2019
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44. Synthesis, in vitro and in vivo biological evaluation of substituted 3-(5-imidazo[2,1-b]thiazolylmethylene)-2-indolinones as new potent anticancer agents.
- Author
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Morigi R, Locatelli A, Leoni A, Rambaldi M, Bortolozzi R, Mattiuzzo E, Ronca R, Maccarinelli F, Hamel E, Bai R, Brancale A, and Viola G
- Subjects
- Antineoplastic Agents chemistry, Apoptosis drug effects, Caspase 3 metabolism, Caspase 9 metabolism, Cell Proliferation drug effects, Chemistry Techniques, Synthetic, Down-Regulation drug effects, Drug Screening Assays, Antitumor, Enzyme Activation drug effects, G2 Phase drug effects, HeLa Cells, Humans, Indoles chemistry, Mitochondria drug effects, Mitochondria metabolism, Structure-Activity Relationship, Antineoplastic Agents chemical synthesis, Antineoplastic Agents pharmacology, Indoles chemical synthesis, Indoles pharmacology
- Abstract
A small library of 3-(5-imidazo[2,1-b]thiazolylmethylene)-2-indolinones has been synthesized and screened according to protocols available at the National Cancer Institute (NCI). Some derivatives were potent antiproliferative agents, showing GI
50 values in the nanomolar range. Remarkably, when most active compounds against leukemia cells were tested in human peripheral blood lymphocytes from healthy donors, were 100-200 times less cytotoxic. Some compounds, selected by the Biological Evaluation Committee of NCI, were examined to determine tubulin assembly inhibition. Furthermore, flow cytometric studies performed on HeLa, HT-29, and A549 cells, showed that compounds 14 and 25 caused a block in the G2/M phase. Interestingly, these derivatives induced apoptosis through the mitochondrial death pathway, causing in parallel significant activation of both caspase-3 and -9, PARP cleavage and down-regulation of the anti-apoptotic proteins Bcl-2 and Mcl-1. Finally, compound 25 was also tested in vivo in the murine BL6-B16 melanoma and E0771 breast cancer cells, causing in both cases a significant reduction in tumor volume., (Copyright © 2019 Elsevier Masson SAS. All rights reserved.)- Published
- 2019
- Full Text
- View/download PDF
45. DNA damage and genome instability by G-quadruplex ligands are mediated by R loops in human cancer cells.
- Author
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De Magis A, Manzo SG, Russo M, Marinello J, Morigi R, Sordet O, and Capranico G
- Subjects
- Aminoquinolines, Cell Line, Tumor, Genes, BRCA2, Humans, Ligands, Picolinic Acids, DNA Damage, G-Quadruplexes, Genomic Instability, Neoplasms genetics
- Abstract
G quadruplexes (G4s) and R loops are noncanonical DNA structures that can regulate basic nuclear processes and trigger DNA damage, genome instability, and cell killing. By different technical approaches, we here establish that specific G4 ligands stabilize G4s and simultaneously increase R-loop levels within minutes in human cancer cells. Genome-wide mapping of R loops showed that the studied G4 ligands likely cause the spreading of R loops to adjacent regions containing G4 structures, preferentially at 3'-end regions of expressed genes, which are partially ligand-specific. Overexpression of an exogenous human RNaseH1 rescued DNA damage induced by G4 ligands in BRCA2 -proficient and BRCA2 -silenced cancer cells. Moreover, even if the studied G4 ligands increased noncanonical DNA structures at similar levels in nuclear chromatin, their cellular effects were different in relation to cell-killing activity and stimulation of micronuclei, a hallmark of genome instability. Our findings therefore establish that G4 ligands can induce DNA damage by an R loop-dependent mechanism that can eventually lead to different cellular consequences depending on the chemical nature of the ligands., Competing Interests: The authors declare no conflict of interest.
- Published
- 2019
- Full Text
- View/download PDF
46. Psychomotor agitation in subjects hospitalized for an acute exacerbation of Schizophrenia.
- Author
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Sacchetti E, Valsecchi P, Tamussi E, Paulli L, Morigi R, and Vita A
- Subjects
- Acute Disease, Adult, Antipsychotic Agents therapeutic use, Anxiety diagnosis, Anxiety psychology, Anxiety therapy, Female, Humans, Male, Middle Aged, Psychomotor Agitation therapy, Retrospective Studies, Schizophrenia therapy, Severity of Illness Index, Hospitalization trends, Psychomotor Agitation diagnosis, Psychomotor Agitation psychology, Schizophrenia diagnosis, Schizophrenic Psychology
- Abstract
The aims of this study were to establish the prevalence of moderate and severe psychomotor agitation in patients hospitalized for an active phase of schizophrenia, the associations between psychomotor agitation and patients' demographic and clinical variables, the intra-individual stability of the agitated/non-agitated dichotomy in independent psychotic breakdowns. The study was performed on a database relative to 630 inpatients hospitalized with a diagnosis of schizophrenia. Psychomotor agitation was measured with the Positive and Negative Syndrome Scale - Excited Component (PANSS-EC). Prevalence of moderate and severe psychomotor agitation was 40.5% and 23.7%, respectively. Non-agitated patients were older, with longer illness history and duration of untreated psychosis, were more frequently on antipsychotic medication, had lower incidence of recent use of substances, and functioned better before the index hospitalization than moderately and/or severely agitated patients. Non-agitated patients had lower scores for total PANSS and Emsley's positive and anxiety dimensions. Compared with the severely agitated group, non-agitated and moderately agitated patients scored more in Emsley's depression dimension. Poor functioning before index hospital admission, higher scores for negative subscale and Emsley's positive dimension and use of substances exerted an effect on risk of psychomotor agitation., (Copyright © 2018. Published by Elsevier B.V.)
- Published
- 2018
- Full Text
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47. Investigation on the Effects of Antimicrobial imidazo[2,1-b]thiazole Derivatives on the Genitourinary Microflora.
- Author
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Morigi R, Vitali B, Prata C, Palomino RAN, Graziadio A, Locatelli A, Rambaldi M, and Leoni A
- Subjects
- Anti-Bacterial Agents chemical synthesis, Antifungal Agents chemical synthesis, Antifungal Agents pharmacology, Antineoplastic Agents chemical synthesis, Antineoplastic Agents pharmacology, Bifidobacterium drug effects, Econazole pharmacology, HeLa Cells, Humans, Imidazoles chemical synthesis, Lactobacillus drug effects, Microbial Sensitivity Tests, Thiazoles chemical synthesis, Urogenital System microbiology, Anti-Bacterial Agents pharmacology, Imidazoles pharmacology, Thiazoles pharmacology
- Abstract
Background: Fused five-membered heterocyclic rings containing bridgehead nitrogen atom are particularly versatile in the field of medicinal chemistry because of their different biological activities. Among them, the imidazo[2,1-b]thiazole is an attractive fused heterocyclic core that has been extensively studied., Objective: The aim of the current study was to study the therapeutic applications of imidazo[2,1- b]thiazole derivatives as antimicrobial agents for the treatment of genitourinary infections., Method: A traditional synthetic methodology was involved to obtain a small series of imidazothiazole derivatives., Results: Herein, we report the antimicrobial activity of the imidazo[2,1-b]thiazole or imidazo[2,1- b]thiazolidine derivatives against selected fungi, Gram-positive and Gram-negative bacteria. Moreover, experiments were carried out to investigate the interference towards the endogenous microbiota., Conclusion: The most interesting of the series are the thiocyano derivatives (19, 23) showing a good profile for the treatment of genitourinary infections: a spectrum of activity covering both bacteria and fungi together with a reduced impact versus critical lines of Lactobacillus exerting defense against pathogens., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)
- Published
- 2018
- Full Text
- View/download PDF
48. Occupation and first episode psychosis in Northern Italy: better outcomes for migrants.
- Author
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Tarricone I, Morgan C, Boydell J, Panigada S, Morigi R, Braca M, Sutti E, Boldri P, Di Forti M, Murray RM, and Berardi D
- Subjects
- Adult, Female, Humans, Italy epidemiology, Male, Young Adult, Occupations statistics & numerical data, Outcome Assessment, Health Care statistics & numerical data, Psychotic Disorders epidemiology, Psychotic Disorders psychology, Transients and Migrants psychology, Transients and Migrants statistics & numerical data
- Abstract
Aims: Many studies show that migrants have a higher incidence of psychosis compared to natives, but the influence of migration on psychosis outcomes is little investigated. We aimed to evaluate the occupational outcomes of a first episode psychosis (FEP) sample in Bologna (Northern Italy)., Methods: An incidence cohort of FEP patients presenting at the Bologna West Community Mental Health Centers between 2002 and 2009 was assessed at the baseline and at 12th month follow-up. Return to school or work was used as occupational outcome., Results: Most of the patients (82.8%) were still in contact at 12 months. Migrants showed significantly higher rate of return to work compared to natives (adjusted OR 4.45, 95% CI 1.55-12.76)., Conclusions: First generation migrants had better occupational outcomes. Further cross-cultural studies are needed to further explain these findings., (© 2016 John Wiley & Sons Australia, Ltd.)
- Published
- 2017
- Full Text
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49. 1,4-Anthraquinone: A new useful pre-column reagent for the determination of N-acetylcysteine and captopril in pharmaceuticals by high performance liquid chromatography.
- Author
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Gatti R and Morigi R
- Subjects
- Acetylcysteine, Anthraquinones, Captopril, Indicators and Reagents, Reproducibility of Results, Chromatography, High Pressure Liquid
- Abstract
1,4-Anthraquinone (ANQ) is proposed as a novel pre-column reagent for high performance liquid chromatography (HPLC) determination of N-acetylcysteine (NAC) and captopril (CAP) in pharmaceutical formulations. The derivatization reactions were carried out at room temperature: NAC at pH 8 for 1min, while CAP at pH 7.5 for 20min. Both reactions reached completeness at a reagent to thiol molar ratio of about 2.5. The synthesised derivatives were characterized by
1 H NMR and IR. The chromatographic separations were performed on a C18 Phenomenex Synergi Fusion 4μm (250mm×4.6mm I.D.) stainless steel column with detection at λ=300nm. The mobile phase consisted of methanol/triethylammonium (TEA) phosphate buffer (pH 3; 0.05mol/L) 75:25 (v/v) at a flow-rate of 0.4mL/min for NAC and 88:12 (v/v), at a flow-rate of 0.6mL/min for CAP. The validation parameters (linearity, sensitivity, accuracy, precision, specificity and stability) were highly satisfactory. Linear response was observed (determination coefficient ≥0.9996). Detection limits were about 8 and 18ng/mL for NAC and CAP, respectively. Intra-day precision (relative standard deviation, R.S.D.) was ≤1.58%, for thiol to internal standard (IS) peak area ratio and ≤0.33%, for thiol and IS retention times (tR ), without significant differences between intra- and inter-day data. Thiol recovery studies were satisfactory (99.50%) with R.S.D. ≤0.56%. The results highlight the high sensitivity of the method and the remarkable reactivity and selectivity of the reagent towards the thiol function. The developed method is suitable for the quality control of both thiols in commercial products. The method can be applied in any analytical laboratory not requiring a sophisticated instrumentation., (Copyright © 2017 Elsevier B.V. All rights reserved.)- Published
- 2017
- Full Text
- View/download PDF
50. Toward the Development of Specific G-Quadruplex Binders: Synthesis, Biophysical, and Biological Studies of New Hydrazone Derivatives.
- Author
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Amato J, Morigi R, Pagano B, Pagano A, Ohnmacht S, De Magis A, Tiang YP, Capranico G, Locatelli A, Graziadio A, Leoni A, Rambaldi M, Novellino E, Neidle S, and Randazzo A
- Subjects
- Cell Proliferation drug effects, DNA drug effects, Dose-Response Relationship, Drug, Humans, Hydrazones chemical synthesis, Hydrazones chemistry, Molecular Docking Simulation, Molecular Structure, Structure-Activity Relationship, Tumor Cells, Cultured, G-Quadruplexes drug effects, Hydrazones pharmacology
- Abstract
G-Quadruplex-binding compounds are currently perceived as possible anticancer therapeutics. Here, starting from a promising lead, a small series of novel hydrazone-based compounds were synthesized and evaluated as G-quadruplex binders. The in vitro G-quadruplex-binding properties of the synthesized compounds were investigated employing both human telomeric and oncogene promoter G-quadruplexes with different folding topologies as targets. The present investigation led to the identification of potent G-quadruplex stabilizers with high selectivity over duplex DNA and preference for one G-quadruplex topology over others. Among them, selected derivatives have been shown to trap G-quadruplex structures in the nucleus of cancer cells. Interestingly, this behavior correlates with efficient cytotoxic activity in human osteosarcoma and colon carcinoma cells.
- Published
- 2016
- Full Text
- View/download PDF
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