33 results on '"Massimiliano Granaiola"'
Search Results
2. Cancer fighting cancer: synthesis of the new heterocyclic system diimidazo[1,2-a:1,2-c]pyrimidine
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Aldo Andreani, Massimiliano Granaiola, Alberto Leoni, Alessandra Locatelli, Rita Morigi, Mirella Rambaldi, Gianluca Giorgi, and Laura Salvini
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Organic chemistry ,QD241-441 - Published
- 2002
- Full Text
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3. 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
4. Antitumor activity and COMPARE analysis of bis-indole derivatives
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Cecilia Prata, Alessandra Locatelli, Alberto Leoni, Cristiana Caliceti, Francesco Vieceli Dalla Sega, Silvia Burnelli, Aldo Andreani, Robert H. Shoemaker, Massimiliano Granaiola, Laura Landi, Rita Morigi, Lucilla Varoli, Mirella Rambaldi, Andreani A., Burnelli S., Granaiola M., Leoni A., Locatelli A., Morigi R., Rambaldi M., Varoli L., Landi L., Prata C., Vieceli Dalla Sega F., Caliceti C., and Shoemaker R.H
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Indoles ,Stereochemistry ,Clinical Biochemistry ,Pharmaceutical Science ,Antineoplastic Agents ,Biochemistry ,Chemical synthesis ,ANTITUMOR ,Inhibitory Concentration 50 ,Structure-Activity Relationship ,chemistry.chemical_compound ,In vivo ,Cell Line, Tumor ,Neoplasms ,Drug Discovery ,Pyridine ,COMPARE ,Humans ,Moiety ,Molecular Biology ,Cell Proliferation ,chemistry.chemical_classification ,Indole test ,Molecular Structure ,Bicyclic molecule ,INDOLE ,Organic Chemistry ,chemistry ,Lactam ,NQO1 ,Molecular Medicine ,Drug Screening Assays, Antitumor ,PIRIDINE ,Lactone - Abstract
This paper reports the synthesis of new derivatives (formed by two indole systems separated by a central moiety) analogous of potent antitumor agents previously described. The activity of the bis-indoles bearing a pyridine core confirms the good result described in the previous paper and compound 4c was chosen for the first in vivo experiment (Hollow Fiber Assay). COMPARE analysis and structure–activity relationships were also considered. Contrary to data reported by other Authors, no correlations were found between antitumor activity and NQO1 induction.
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- 2010
5. 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
6. 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
7. 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
8. Effects of new ubiquinone-imidazo[2,1-b]thiazoles on mitochondrial complex I (NADH-ubiquinone reductase) and on mitochondrial permeability transition pore
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Rita Morigi, Aldo Andreani, Massimiliano Granaiola, Christian Bergamini, Mirella Rambaldi, Romana Fato, Alberto Leoni, Giorgio Lenaz, Maurizio Recanatini, Alessandra Locatelli, ANDREANI A., GRANAIOLA M., LEONI A., LOCATELLI A., MORIGI R., RAMBALDI M., RECANATINI M., LENAZ G., FATO R., and BERGAMINI C.
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Male ,Ubiquinone ,Stereochemistry ,Clinical Biochemistry ,Pharmaceutical Science ,Mitochondria, Liver ,Mitochondrion ,Biochemistry ,Chemical synthesis ,Mitochondria, Heart ,Permeability ,chemistry.chemical_compound ,Drug Discovery ,Animals ,Rats, Wistar ,Inner mitochondrial membrane ,Molecular Biology ,Electron Transport Complex I ,Organic Chemistry ,Imidazoles ,Rotenone ,Benzoquinone ,Rats ,Quinone ,Enzyme Activation ,Thiazoles ,Membrane ,chemistry ,Mitochondrial permeability transition pore ,Molecular Medicine ,Cattle - Abstract
In this work we describe the synthesis of a series of imidazo[2,1- b ]thiazoles and 2,3-dihydroimidazo[2,1- b ]thiazoles connected by means of a methylene bridge to CoQ 0 . These compounds were tested as specific inhibitors of the NADH:ubiquinone reductase activity in mitochondrial membranes. The imidazothiazole system when bound to the quinone ring in place of the isoprenoid lateral side chain, may increase the inhibitory effect (with an IC 50 for NADH-Q 1 activity ranging between 0.25 and 0.96 μM) whereas the benzoquinone moiety seems to lose the capability to accept electrons from complex I as indicated by very low maximal velocity elicited by the compounds tested. Moreover the low rotenone sensitivity for almost all of these compounds suggests that they are only partially able to interact with the physiological ubiquinone-reduction site. The compounds were investigated for the capability of increasing the permeability transition of the inner mitochondrial membrane in isolated mitochondria. Unlike CoQ 0 , which is considered a mitochondrial membrane permeability transition inhibitor, the new compounds were inducers.
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- 2004
9. Substituted E -3-(2-Chloro-3-indolylmethylene)1,3-dihydroindol-2-ones with antitumor activity
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Massimiliano Granaiola, Giovanna Farruggia, Alessandra Locatelli, Lanfranco Masotti, Alberto Leoni, Rita Morigi, Aldo Andreani, Vida Garaliene, Mirella Rambaldi, Andreani A., Granaiola M., Leoni A., Locatelli A., Morigi R., Rambaldi M., Garaliene V., Farruggia G., and Masotti L.
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Indoles ,Stereochemistry ,Clinical Biochemistry ,Mitosis ,Pharmaceutical Science ,Antineoplastic Agents ,Breast Neoplasms ,In Vitro Techniques ,Biochemistry ,Chemical synthesis ,Inhibitory Concentration 50 ,Structure-Activity Relationship ,Cell Line, Tumor ,Drug Discovery ,medicine ,Humans ,Moiety ,Structure–activity relationship ,Cytotoxicity ,Melanoma ,Molecular Biology ,Ovarian Neoplasms ,Chemistry ,Organic Chemistry ,Cell cycle ,In vitro ,Mechanism of action ,Cell culture ,Molecular Medicine ,Female ,medicine.symptom ,Cell Division - Abstract
The synthesis and antitumor activity of a new series of E-3-(2-chloro-3-indolylmethylene)1,3-dihydroindol-2-ones is described. Several compounds were active on the primary test (three human cell lines) and entered the second level (60 human cell lines). All of them were potent growth inhibitors with GI(50) ranging from -5.32 to -7.27. Four are now under review by BEC (Biological Evaluation Committee of the NCI). The most potent antitumor derivatives were also evaluated as cardiotonic agents (in view of a possible coanthracyclinic activity). In order to find a possible mechanism of action their effects on cell cycle progression in an adenocarcinoma cell line (HT29) were tested, evidencing that these molecules are able to block HT29 in mitosis. The introduction of new substituents in the indolinone moiety while maintaining the same chloroindole portion generated interesting derivatives. 3-(2-Chloro-5-methoxy-6-methyl-3-indolylmethylene)5-hydroxy-1,3-dihydroindol-2-one was the most active of the whole series. It was more potent than vincristine against seven of the nine tumors considered. Moreover it was selective towards some cell lines such as MDA-MB-435 (breast), OVCAR-3 (ovarian) and SK-MEL-28 (melanoma). Even the introduction of a benzyl ring at the nitrogen of the chloroindole portion, gave rise to potent compounds.
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- 2004
10. 2-[(E)-3-(6-chloroimidazo[2,1-b]thiazol-5-yl)prop-2-enyl]-5,6-dimethoxy-3-methyl-1,4-benzoquinone: a new inhibitor of NADH dehydrogenase with antitumor activity
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Massimiliano Granaiola, Romana Fato, Alberto Leoni, Rita Morigi, Christian Bergamini, Aldo Andreani, Alessandra Locatelli, Giorgio Lenaz, and Mirella Rambaldi
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chemistry.chemical_classification ,biology ,Stereochemistry ,Organic Chemistry ,NADH dehydrogenase ,Biological activity ,Electron acceptor ,Benzoquinone ,Quinone ,1,4-Benzoquinone ,lcsh:QD241-441 ,chemistry.chemical_compound ,chemistry ,lcsh:Organic chemistry ,biology.protein ,Moiety ,Derivative (chemistry) - Abstract
In this work we describe the synthesis and the biological activity of 2-[(E)-3-(6chloroimidazo[2,1-b]thiazol-5-yl)prop-2-enyl]-5,6-dimethoxy-3-methyl-1,4-benzoquinone i.e. an imidazothiazole derivative connected to the benzoquinone ring of Q0. This compound was tested as specific inhibitor of the NADH:ubiquinone (UBQ) reductase activity of NADH dehydrogenase in mitochondrial membranes. Binding of the imidazothiazole moiety to the quinone site normally occupied by the isoprenoid lateral side chain increases the inhibitory effect (with an IC50 for NADH-Q1 activity of 0.24 μM) whereas the benzoquinone moiety seems to lose the capability as electron acceptor from Complex I. The new compound was also tested as potential antitumor agent at the National Cancer Institute.
- Published
- 2004
11. Cancer fighting cancer: synthesis of the new heterocyclic system diimidazo[1,2-a:1,2-c]pyrimidine
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Rita Morigi, Gianluca Giorgi, Massimiliano Granaiola, Aldo Andreani, Laura Salvini, Alberto Leoni, Mirella Rambaldi, and Alessandra Locatelli
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lcsh:QD241-441 ,chemistry.chemical_compound ,Pyrimidine ,lcsh:Organic chemistry ,Chemistry ,Organic Chemistry ,medicine ,Organic chemistry ,Cancer ,medicine.disease ,Combinatorial chemistry - Abstract
One of our projects devoted to the synthesis of potential antitumor agents is called “Cancer Fighting Cancer”. This brought us to synthesize the new heterocyclic system, diimidazo-[1,2a:1,2-c]-pyrimidine, which is a key intermediate for the synthesis of antitumor derivatives. The structure of this compound was demonstrated by means of NMR and MS experiments.
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- 2002
12. Synthesis and antitubercular activity of imidazo[2,1-b]thiazoles
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Massimiliano Granaiola, Mirella Rambaldi, Rita Morigi, Aldo Andreani, Alberto Leoni, and Alessandra Locatelli
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Pharmacology ,Magnetic Resonance Spectroscopy ,Spectrophotometry, Infrared ,Bicyclic molecule ,Imidazothiazole ,Stereochemistry ,Organic Chemistry ,Antitubercular Agents ,Imidazoles ,Microbial Sensitivity Tests ,Mycobacterium tuberculosis ,General Medicine ,Antimicrobial ,Chemical synthesis ,Thiazoles ,chemistry.chemical_compound ,chemistry ,Drug Discovery ,Thiazole ,Derivative (chemistry) ,Antibacterial agent - Abstract
A number of selected imidazo[2,1-b]thiazoles entered the screening at the Tuberculosis Antimicrobial Acquisition and Coordinating Facility (TAACF) and one of these compounds, 2-chloro-6-phenylimidazo[2,1-b]thiazole, showed antitubercular activity. On this basis we planned the synthesis of new analogues bearing a substituted ring at the 6 position. For one compound only (2-chloro-6-p-chlorophenylimidazo[2,1-b]thiazole) the 5-nitroso derivative was also prepared. The antitubercular activity of these compounds was compared with the known analogues lacking the chlorine at the 2 position. 5-Nitroso-6-p-chlorophenylimidazo[2,1-b]thiazole showed potent antitubercular activity.
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- 2001
13. Synthesis and Chemiluminescent High Throughput Screening for Inhibition of Acetylcholinesterase Activity by Imidazo[2,1-b]thiazole Derivatives
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Massimo Guardigli, Aldo Roda, Aldo Andreani, Alberto Leoni, Massimiliano Granaiola, Alessandra Locatelli, Mirella Rambaldi, Rita Morigi, ALDO ANDREANI, MASSIMILIANO GRANAIOLA, MASSIMO GUARDIGLI, ALBERTO LEONI, ALESSANDRA LOCATELLI, RITA MORIGI, MIRELLA RAMBALDI, and ALDO RODA
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medicine.drug_class ,IMIDAZO[2 ,High-throughput screening ,Neuromuscular transmission ,Drug Evaluation, Preclinical ,Carboxamide ,Chemical synthesis ,Sensitivity and Specificity ,law.invention ,Structure-Activity Relationship ,chemistry.chemical_compound ,law ,Drug Discovery ,medicine ,Organic chemistry ,Thiazole ,Chemiluminescence ,Pharmacology ,biology ,Bicyclic molecule ,Molecular Structure ,ALZHEIMERE'S DISEASE ,Organic Chemistry ,Imidazoles ,General Medicine ,Combinatorial chemistry ,Acetylcholinesterase ,BISAMMONIUM SALT ,Thiazoles ,Inhibitory potency ,ANTIACETYLCHOLINESTERASE ACTIVITY ,chemistry ,Enzyme inhibitor ,CHEMILUMINESCENT ,Luminescent Measurements ,biology.protein ,1-B]THIAZOLE - Abstract
The synthesis of a new series of imidazo[2,1-b]thiazole derivatives is described. They were tested as acetylcholinesterase inhibitors by means of a chemiluminescent method suitable for high throughput screening. The compounds without quaternization had no appreciable inhibitory potency probably because they are poorly soluble in water. The corresponding quaternized compounds were good inhibitors with activity related to the spacer employed.
- Published
- 2006
14. 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
15. 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.
- Published
- 2012
16. 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
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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
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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.
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- 2010
17. Bis-guanylhydrazone diimidazo[1,2-a:1,2-c]pyrimidine as a novel and specific G-quadruplex binding motif
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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
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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.
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- 2010
18. Antitumor Activity of Bis-Indole Derivatives
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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
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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
19. 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
20. Antitumor Activity of New Substituted 3-(5-Imidazo[2,1-b]thiazolylmethylene)-2-indolinones and 3-(5-Imidazo[2,1-b]thiadiazolylmethylene)-2-indolinones: Selectivity Against Colon Tumor Cells and Effect on Cell Cycle-Related Events
- Author
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Natalia Calonghi, Silvia Burnelli, Manuela Voltattorni, Lucilla Varoli, Alessandra Locatelli, Maddalena Zini, Aldo Andreani, Rita Morigi, Alberto Leoni, Lanfranco Masotti, Massimiliano Granaiola, Claudio Stefanelli, Concettina Cappadone, Robert H. Shoemaker, Mirella Rambaldi, Andreani A., Burnelli S., Granaiola M., Leoni A., Locatelli A., Morigi R., Rambaldi M., Varoli L., Calonghi N., Cappadone C., Voltattorni M., Zini M., Stefanelli C., Masotti L., and Shoemaker R.H
- Subjects
G2 Phase ,Indoles ,Cell cycle checkpoint ,Antineoplastic Agents ,Apoptosis ,ANTITUMORALI ,Ornithine decarboxylase ,Structure-Activity Relationship ,Thiadiazoles ,Drug Discovery ,Polyamines ,Tumor Cells, Cultured ,medicine ,Humans ,IMIDAZOTIAZOLI ,Cell Proliferation ,chemistry.chemical_classification ,Binding Sites ,INDOLI ,Dose-Response Relationship, Drug ,Molecular Structure ,Chemistry ,Cell Cycle ,Stereoisomerism ,Ornithine Decarboxylase Inhibitors ,Cell cycle ,CICLO CELLULARE ,In vitro ,Thiazoles ,CARCINOMA DEL COLON HT-29 ,Enzyme ,Biochemistry ,Mechanism of action ,Cell culture ,Drug Design ,Cancer research ,Molecular Medicine ,Drug Screening Assays, Antitumor ,medicine.symptom ,HT29 Cells ,Cell Division - Abstract
The synthesis of new 3-(5-imidazo[2,1-b]thiazolylmethylene)-2-indolinones and 3-(5-imidazo[2,1-b]thiadiazolylmethylene)-2-indolinones is reported. The antitumor activity was evaluated according to the protocols available at the National Cancer Institute (NCI), Bethesda, MD. To investigate the mechanism of action of the most potent antitumor agent of this series, its effect on growth of HT-29 colon carcinoma cells was studied. Its ability to inhibit cellular proliferation was mediated by cell cycle arrest at the G2/M phase, accompanied by inhibition of ornithine decarboxylase (ODC), the limiting enzyme of polyamine synthesis, and followed by induction of apoptosis.
- Published
- 2008
21. Substituted E-3-(2-chloro-3-indolylmethylene)1,3-dihydroindol-2-ones with antitumor activity. Effect on the cell cycle and apoptosis
- Author
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Natalia Calonghi, Lanfranco Masotti, Giovanna Farruggia, Rita Morigi, Lucilla Varoli, Maddalena Zini, Claudio Stefanelli, Massimiliano Granaiola, Mirella Rambaldi, Concettina Cappadone, Aldo Andreani, Silvia Burnelli, Alessandra Locatelli, Alberto Leoni, Andreani A., Burnelli S., Granaiola M., Leoni A., Locatelli A., Morigi R., Rambaldi M., Varoli L., Calonghi N., Cappadone C., Farruggia G., Zini M., Stefanelli C., and Masotti L.
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Indoles ,Magnetic Resonance Spectroscopy ,Stereochemistry ,Antineoplastic Agents ,Pharmacology ,Chemical synthesis ,chemistry.chemical_compound ,Cell Line, Tumor ,Drug Discovery ,Humans ,Cytotoxic T cell ,Ovarian Neoplasms ,Cell Death ,Chemistry ,Cell Cycle ,INDOLE DERIVATIVES ,Biological activity ,Cell cycle ,In vitro ,ANTITUMOR ACTIVITY ,APOPTOSIS ,Cell culture ,Apoptosis ,Molecular Medicine ,Female ,Drug Screening Assays, Antitumor ,Growth inhibition ,Cell Division - Abstract
The synthesis and antitumor activity of new E-3-(2-chloro-3-indolylmethylene)1,3-dihydroindol-2-ones is described. They were studied at the National Cancer Institute, taking into consideration the 50% growth inhibitory power (pGI50), the cytostatic effect (pTGI = total growth inhibition), and the cytotoxic effect (pLC50). All the compounds were potent growth inhibitors, with mean pGI50 ranging from 5.26 to 7.72. They were also analyzed with NCI COMPARE algorithm. Further studies were dedicated to the effects on the cell cycle and apoptosis.
- Published
- 2007
22. 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(1)
- Author
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Aldo, Andreani, Silvia, Burnelli, Massimiliano, Granaiola, Alberto, Leoni, Alessandra, Locatelli, Rita, Morigi, Mirella, Rambaldi, Lucilla, Varoli, Giovanna, Farruggia, Claudio, Stefanelli, Lanfranco, Masotti, and Mark W, Kunkel
- Subjects
Membrane Potential, Mitochondrial ,Adenosylmethionine Decarboxylase ,Cell Death ,Molecular Structure ,Cell Cycle ,Hydrazones ,Antineoplastic Agents ,HL-60 Cells ,Structure-Activity Relationship ,Thiazoles ,Neoplasms ,Tumor Cells, Cultured ,Humans ,Drug Screening Assays, Antitumor - 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
23. Antitumor activity of substituted E-3-(3,4,5-trimethoxybenzylidene)-1,3-dihydroindol-2-ones1
- Author
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Aldo, Andreani, Silvia, Burnelli, Massimiliano, Granaiola, Alberto, Leoni, Alessandra, Locatelli, Rita, Morigi, Mirella, Rambaldi, Lucilla, Varoli, and Mark W, Kunkel
- Subjects
Structure-Activity Relationship ,Indoles ,Humans ,Antineoplastic Agents ,Stereoisomerism ,Drug Screening Assays, Antitumor - 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
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. 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
27. 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
28. Synthesis and antitumor activity of 1,5,6-substituted E-3-(2-chloro-3-indolylmethylene)-1,3-dihydroindol-2-ones
- Author
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Rita Morigi, Mirella Rambaldi, Vida Garaliene, Alessandra Locatelli, Alberto Leoni, Aldo Andreani, and Massimiliano Granaiola
- Subjects
Indoles ,Stereochemistry ,Guinea Pigs ,Antineoplastic Agents ,Chemical synthesis ,chemistry.chemical_compound ,Structure-Activity Relationship ,Drug Discovery ,CDC2 Protein Kinase ,Tumor Cells, Cultured ,Animals ,Humans ,Cytotoxicity ,Cyclin-dependent kinase 1 ,biology ,Bicyclic molecule ,Stereoisomerism ,Papillary Muscles ,Myocardial Contraction ,In vitro ,Tubulin ,chemistry ,Cell culture ,biology.protein ,Lactam ,Molecular Medicine ,Drug Screening Assays, Antitumor ,Cell Division - Abstract
Synthesis and antitumor activity of new E-3-(2-chloro-3-indolylmethylene)-1,3-dihydroindol-2-ones are described. All compounds prepared were active in the primary test (three human cell lines) and entered the second level (60 human cell lines). The most active antitumor derivatives bear the same substituents in the chloroindole ring and are not CDK1 inhibitors. A COMPARE analysis showed that they could act as tubulin binders. In most cell lines, E-3-(2-chloro-5-methoxy-6-methyl-3-indolylmethylene)-1,3-dihydroindol-2-one was a growth inhibitor more potent than vincristine.
- Published
- 2002
29. Synthesis and screening for antiacetylcholinesterase activity of (1-benzyl-4-oxopiperidin-3-ylidene)methylindoles and -pyrroles related to donepezil
- Author
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Aldo Roda, Massimo Guardigli, Massimiliano Granaiola, Mirella Rambaldi, Alessandra Locatelli, Rita Morigi, Andrea Cavalli, Alberto Leoni, Aldo Andreani, and Maurizio Recanatini
- Subjects
Models, Molecular ,Indoles ,Molecular model ,Stereochemistry ,Drug Evaluation, Preclinical ,Chemical synthesis ,chemistry.chemical_compound ,Structure-Activity Relationship ,Piperidines ,Drug Discovery ,medicine ,Structure–activity relationship ,Moiety ,Donepezil ,Pyrroles ,Nootropic Agents ,chemistry.chemical_classification ,biology ,Acetylcholinesterase ,Enzyme ,chemistry ,Enzyme inhibitor ,Indans ,Luminescent Measurements ,biology.protein ,Molecular Medicine ,medicine.drug - Abstract
The design, synthesis, and rapid evaluation of a new class of acetylcholinesterase (AChE) inhibitors related to donepezil are reported. A molecular dynamics simulation of the complex between AChE and one representative compound of the series showed a possible inhibitor binding mode in which favorable interactions are formed between the benzylpiperidinone moiety and some active-site residues. The biochemical evaluation of this newly synthesized series was performed using a chemiluminescent method suitable for high-throughput screening.
- Published
- 2001
30. Antitumor Activity of Bis-indole Derivatives.
- Author
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Aldo Andreani, Silvia Burnelli, Massimiliano Granaiola, Alberto Leoni, Alessandra Locatelli, Rita Morigi, Mirella Rambaldi, Lucilla Varoli, Laura Landi, Cecilia Prata, Michael V. Berridge, Carole Grasso, Heinz-Herbert Fiebig, Gerhard Kelter, Angelika M. Burger, and Mark W. Kunkel
- Published
- 2008
- Full Text
- View/download PDF
31. New Antitumor Imidazo[2,1-b]thiazole Guanylhydrazones and Analogues1.
- 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, and Robert H. Shoemaker
- Published
- 2008
- Full Text
- View/download PDF
32. Substituted E-3-(2-Chloro-3-indolylmethylene)1,3-dihydroindol-2-ones with Antitumor Activity. Effect on the Cell Cycle and Apoptosis1.
- 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, and Lanfranco Masotti
- Published
- 2007
- Full Text
- View/download PDF
33. 2-[(E)-3-(6-chloroimidazo[2,1-b]thiazol-5-ylprop-2-enyl]5,6-dimethoxy-3-methyl-1,4-benzo quinone: a new inhibitor of NADH dehydrogenase with antitumor activity
- Author
-
ANDREANI, ALDO, GRANAIOLA, MASSIMILIANO, LEONI, ALBERTO, LOCATELLI, ALESSANDRA, MORIGI, RITA, RAMBALDI, MIRELLA, LENAZ, GIORGIO, FATO, ROMANA, BERGAMINI, CHRISTIAN, ALDO ANDREANI, MASSIMILIANO GRANAIOLA, ALBERTO LEONI, ALESSANDRA LOCATELLI, RITA MORIGI, MIRELLA RAMBALDI, GIORGIO LENAZ, ROMANA FATO, and CHRISTIAN BERGAMINI
- Subjects
IMIDAZOTHIAZOLE ,COENZYMEQ ,QUINONE ,ANTITUMOR ACTIVITY - Published
- 2004
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