15 results on '"Antonietta Di Cristina"'
Search Results
2. Identification of a Terphenyl Derivative that Blocks the Cell Cycle in the G0−G1 Phase and Induces Differentiation in Leukemia Cells
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Marinella Roberti, Manlio Tolomeo, Nicola Gebbia, Daniele Simoni, Stefania Grimaudo, Antonietta Di Cristina, Daniela Pizzirani, Maurizio Recanatini, Vincenzo Abbadessa, ROBERTI M, PIZZIRANI D, RECANATINI M, SIMONI D, GRIMAUDO S, DI CRISTINA A, ABBADESSA V, GEBBIA N, TOLOMEO M, Roberti M., Pizzirani D., Recanatini M., Simoni D., Grimaudo S., Di Cristina A., Abbadessa V., Gebbia N., and Tolomeo M.
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Stereochemistry ,Cellular differentiation ,Fusion Proteins, bcr-abl ,Antineoplastic Agents ,Apoptosis ,Resveratrol ,Resting Phase, Cell Cycle ,Chemical synthesis ,Structure-Activity Relationship ,chemistry.chemical_compound ,Leukemia, Promyelocytic, Acute ,Cell Line, Tumor ,Terphenyl Compounds ,Terphenyl ,Stilbenes ,Drug Discovery ,Humans ,Structure–activity relationship ,ATP Binding Cassette Transporter, Subfamily B, Member 1 ,G1 Phase ,Cell Differentiation ,Cell cycle ,In vitro ,chemistry ,Drug Resistance, Neoplasm ,Cell culture ,Molecular Medicine ,Drug Screening Assays, Antitumor - Abstract
To further explore the SAR of resveratrol-related trans-stilbene derivatives, here we describe the synthesis of (a) a series of 3,5-dimethoxy analogues in which a variety of substituents were introduced at positions 2', 3', 4', and 5' of the stilbene scaffold and (b) a second group of derivatives (2-phenylnaphthalenes and terphenyls) that incorporate a phenyl ring as a bioisosteric replacement of the stilbene alkenyl bridge. We thoroughly characterized all of the new compounds with respect to their apoptosis-inducing activity and their effects on the cell cycle. One of the new derivatives, 13g, behaved differently from the others, as it was able to block the cell cycle in the G(0)-G(1) phase and also to induce differentiation in acute myelogenous leukemia HL60 cells. Compared to resveratrol, the synthetic terphenyl 13g showed a more potent apoptotic and differentiating activity. Moreover, it was active on both multidrug resistance and Bcr-Abl-expressing cells that were resistant to resveratrol.
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- 2006
3. Novel antiproliferative chimeric compounds with marked histone deacetylase inhibitory activity
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Marinella Roberti, Elisa Giacomini, Alfonso Ciotta, Angela Nebbioso, Maurizio Recanatini, Federico Falchi, Rosaria Maria Pipitone, Antonietta Di Cristina, Stefania Grimaudo, Lucia Altucci, Cristina Ianni, Manlio Tolomeo, Giacomini, E, Nebbioso, Angela, Ciotta, A, Ianni, C, Falchi, F, Roberti, M, Tolomeo, M, Grimaudo, S, Cristina, Ad, Pipitone, Rm, Altucci, Lucia, Recanatini, M., Giacomini E, Nebbioso A, Ciotta A, Ianni C, Falchi F, Roberti M, Tolomeo M, Grimaudo S, Cristina AD, Pipitone RM, Altucci L, Recanatini M, Nebbioso, A, Cristina, AD, Pipitone, RM, Altucci, L, and Recanatini, M
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Multifunctional ligands ,Cell cycle progression ,HDAC inhibition ,Inhibitory postsynaptic potential ,Biochemistry ,Settore BIO/13 - Biologia Applicata ,HDAC ,Drug Discovery ,medicine ,Cytotoxic T cell ,antiproliferative activity ,chimeric compound ,stilbene ,Cancer ,biology ,Chemistry ,ANTIPROLIFERATIVE ACTIVITY ,Organic Chemistry ,multifunctional ligand ,medicine.disease ,Combinatorial chemistry ,Settore CHIM/08 - Chimica Farmaceutica ,Histone ,STILBENES ,biology.protein ,HDAC INHIBITORS ,Epigenetics ,Histone deacetylase ,Chimeric molecules - Abstract
Given our interest in finding potential antitumor agents and in view of the multifactorial mechanistic nature of cancer, in the present work, taking advantage of the multifunctional ligands approach, new chimeric molecules were designed and synthesized by combining in single chemical entities structural features of SAHA, targeting histone deacetylases (HDACs), with substituted stilbene or terphenyl derivatives previously obtained by us and endowed with antiproliferative and pro-apoptotic activity. The new chimeric derivatives were characterized with respect to their cytotoxic activity and their effects on cell cycle progression on different tumor cell lines, as well as their HDACs inhibition. Among the other, trans -6 showed the most interesting biological profile, as it exhibited a strong pro-apoptotic activity in tumor cell lines in comparison with both of its parent compounds and a marked HDAC inhibition.
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- 2014
4. 3-Aryl-2-[1H-benzotriazol-1-yl]acrylonitriles: a novel class of potent tubulin inhibitors
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Antonio Carta, Manlio Tolomeo, Sabrina Pricl, Paolo La Colla, Maurizio Fermeglia, Erik Laurini, Stefania Grimaudo, Roberta Loddo, Giampiero Boatto, Antonietta Di Cristina, Sandra Piras, Maria Silvia Paneni, Rosaria Maria Pipitone, Irene Briguglio, Paola Posocco, Carta, A., Briguglio, I., Piras, S., Boatto, G., la Colla, P., Loddo, R., Tolomeo, M., Grimaudo, S., Di Cristina, A., Pipitone, M. R., Laurini, Erik, Paneni, Maria Silvia, Posocco, Paola, Fermeglia, Maurizio, Pricl, Sabrina, Carta, A, Briguglio, I, Piras, S, Boatto, G, La Colla, P, Loddo, R, Tolomeo, M, Grimaudo, S, Di Cristina, A, Pipitone, R, Laurini, E, Paneni, M, Posocco, P, Fermeglia, M, and Pricl, S
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Models, Molecular ,Magnetic Resonance Spectroscopy ,Molecular model ,Stereochemistry ,Anti-cancer drugs ,Binding, Competitive ,Gas Chromatography-Mass Spectrometry ,Anti-cancer drug ,chemistry.chemical_compound ,Structure-Activity Relationship ,Tubulin ,drug design and development ,computer assisted drug design ,Drug Discovery ,K562 Cell ,medicine ,Structure–activity relationship ,Humans ,Pharmacology ,biology ,Acrylonitrile ,Chemistry ,Aryl ,Organic Chemistry ,Cell Cycle ,General Medicine ,Cell cycle ,Triazoles ,Podophyllotoxin ,Cell culture ,Tubulin Binding Agent ,biology.protein ,Triazole ,Colchicine ,K562 Cells ,Human ,medicine.drug - Abstract
During a screening for compounds that could act against Mycobacterium tuberculosis, a series of new cellular antiproliferative agents was identified. The most cytotoxic molecules were evaluated against a panel of human cell lines derived from hematological and solid human tumors. In particular, (E)-2-(1H-benzo[d] [1,2,3]triazol-1-yl)-3-(4-methoxyphenyl)acrylonitrile (1) was found to be of a potency comparable to etoposide and greater than 6-mercaptopurine in all cell lines tested. Accordingly, a synthesis of a new series of (E)-2-(5,6-dichloro-1H-benzo[d] [1,2,3]triazol-1-yl)-3-(4-R-phenyl)acrylonitriles was conducted in order to extend the studies of structure-activity relationship (SAR) for this class of molecules. With the aim to evaluate if 3-aryl-2-[1H-benzotriazol-1-yl]acrylonitriles were able to act like tubulin binding agents, the effects on cell cycle distribution of the most active compounds (1, 2a, 3 and 4) were analyzed in K562 cells. A detailed molecular modeling study of the putative binding mode of this series of compounds on tubulin is also reported.
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- 2011
5. Synthesis of novel antimitotic agents based on 2-amino-3-aroyl-5-(hetero)arylethynyl thiophene derivatives
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Pier Giovanni Baraldi, Stefania Grimaudo, Antonietta Di Cristina, Ernest Hamel, Rosaria Maria Pipitone, Andrea Brancale, Romeo Romagnoli, Jan Balzarini, Manlio Tolomeo, Olga Cruz-Lopez, Romagnoli, R, Baraldi, PG, Cruz-Lopez, O, Tolomeo, M, Di Cristina, A, Pipitone, RM, Grimaudo, S, Balzarini, J, Brancale, A, and Hamel, E
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Ketone ,Cell division ,Stereochemistry ,Clinical Biochemistry ,Pharmaceutical Science ,Sonogashira coupling ,Uterine Cervical Neoplasms ,Ether ,macromolecular substances ,Thiophenes ,Antimitotic Agents ,Biochemistry ,Chemical synthesis ,Article ,chemistry.chemical_compound ,Mice ,Structure-Activity Relationship ,Thiophene ,Cell Line, Tumor ,Drug Discovery ,Animals ,Humans ,Inhibition of tumor cell growth ,Molecular Biology ,Cell Proliferation ,chemistry.chemical_classification ,Leukemia ,Molecular Structure ,Inhibition of tubulin polymerization ,Cell growth ,Aryl ,Organic Chemistry ,Antiproliferative agents ,chemistry ,Molecular Medicine ,Female - Abstract
Microtubules are dynamic structures that play a crucial role in cellular division and are recognized as an important target for cancer therapy. In search of new compounds with strong antiproliferative activity and simple molecular structure, a new series of 2-amino-3-(3',4',5'-trimethoxybenzoyl)-5-(hetero)aryl ethynyl thiophene derivatives was prepared by the Sonogashira coupling reaction of the corresponding 5-bromothiophenes with several (hetero)aryl acetylenes. When these compounds were analyzed in vitro for their inhibition of cell proliferation, the 2- and 3-thiophenyl acetylene derivatives were the most powerful compounds, both of which exerted cytostatic effects at submicromolar concentrations. In contrast, the presence of a more flexible ethyl chain between the (hetero)aryl and the 5-position of the thiophene ring resulted in significant reduction in activity relative to the 5-(hetero)aryl acetylene substituted derivatives. The effects of a selected series of compounds on cell cycle progression correlated well with their strong antiproliferative activity and inhibition of tubulin polymerization. We found that the antiproliferative effects of the most active compounds were associated with increase of the proportion of cells in the G(2)/M and sub-G(1) phases of the cell cycle. ispartof: Bioorganic & Medicinal Chemistry Letters vol:21 issue:9 pages:2746-51 ispartof: location:England status: published
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- 2011
6. Synthesis, antiproliferative activity, and mechanism of action of a series of 2-{[2E]-3-phenylprop-2-enoylamino}benzamides
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Giuseppe Daidone, Manlio Tolomeo, Benedetta Maggio, Ernest Hamel, Antonietta Di Cristina, Maria Valeria Raimondi, Stella Cascioferro, Salvatore Plescia, Demetrio Raffa, Fabiana Plescia, Ruoli Bai, Stefania Grimaudo, Rosaria Maria Pipitone, Raffa, D, Maggio, B, Plescia, F, Cascioferro, SM, Plescia, S, Raimondi, MV, Daidone, G, Tolomeo, M, Grimaudo, S, Di Cristina, A, Pipitone, RM, Bai R, and Hamel, E
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Pyridines ,medicine.drug_class ,Stereochemistry ,Antineoplastic Agents ,Carboxamide ,Chemical synthesis ,Article ,Polymerization ,Inhibitory Concentration 50 ,Structure-Activity Relationship ,Tubulin ,Cell Line, Tumor ,Drug Discovery ,medicine ,Humans ,Structure–activity relationship ,ortho-Aminobenzoates ,Cytotoxicity ,2-{[2E]-3-phenylprop-2-enoylamino}benzamides, antimitotic agents, cytotoxic activity ,Pharmacology ,Dose-Response Relationship, Drug ,biology ,Chemistry ,Tubulin Modulators ,Cell Cycle ,Organic Chemistry ,General Medicine ,Cell cycle ,Settore CHIM/08 - Chimica Farmaceutica ,Acrylates ,Mechanism of action ,Biochemistry ,Benzamides ,biology.protein ,Drug Screening Assays, Antitumor ,medicine.symptom - Abstract
Several new 2-{[(2E)-3-phenylprop-2-enoyl]amino}benzamides 12a–s and 17t–v were synthesized by stirring in pyridine the (E)-3-(2-R1-3-R2-4-R3-phenyl)acrylic acid chlorides 11c–k and 11t–v with the appropriate anthranilamide derivatives 10a–c or the 5-iodoanthranilic acid 13. Some of the synthesized compounds were evaluated for their in vitro antiproliferative activity against the full NCI tumor cell line panel derived from nine clinically isolated cancer types (leukemia, non-small cell lung, colon, CNS, melanoma, ovarian, renal, prostate and breast). COMPARE analysis, effects on tubulin polymerization in cells and with purified tubulin, and effects on cell cycle distribution for 17t, the most active of the series, indicate that these new antiproliferative compounds act as antitubulin agents.
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- 2011
7. Substituted 2-(3',4',5'-trimethoxybenzoyl)-benzo[b]thiophene derivatives as potent tubulin polymerization inhibitors
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Ernest Hamel, Romeo Romagnoli, Olga Cruz-Lopez, Manlio Tolomeo, Antonietta Di Cristina, Andrea Brancale, Maria Dora Carrion, Pier Giovanni Baraldi, Jan Balzarini, Stefania Grimaudo, Maria Rosaria Pipitone, Romagnoli, R, Baraldi, PG, Carrion, MD, Cruz-Lopez, O, Tolomeo, M, Grimaudo, S, Di Cristina, A, Pipitone, RM, Balzarini, J, Brancale, A, and Hamel, E
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Models, Molecular ,Stereochemistry ,Clinical Biochemistry ,Substituent ,Pharmaceutical Science ,Antineoplastic Agents ,Thiophenes ,Anisoles ,Biochemistry ,Article ,Antineoplastic Agent ,Anisole ,chemistry.chemical_compound ,Structure-Activity Relationship ,Thiophene ,Microtubule ,Tubulin ,Tubulin Modulator ,Cell Line, Tumor ,Neoplasms ,Drug Discovery ,Animals ,Humans ,Molecular Biology ,Cell Proliferation ,biology ,Bicyclic molecule ,Animal ,Cell growth ,Tubulin Modulators ,Organic Chemistry ,Cell Cycle ,Rats ,chemistry ,biology.protein ,Rat ,Neoplasm ,Molecular Medicine ,Growth inhibition ,Human - Abstract
The central role of microtubules in cell division and mitosis makes them a particularly important target for anticancer agents. On our early publication, we found that a series of 2-(3',4',5'-trimethoxybenzoyl)-3-aminobenzo[b]thiophenes exhibited strong antiproliferative activity in the submicromolar range and significantly arrested cells in the G2-M phase of the cell cycle and induced apoptosis. In order to investigate the importance of the amino group at the 3-position of the benzo[b]thiophene skeleton, the corresponding 3-unsubstituted and methyl derivatives were prepared. A novel series of inhibitors of tubulin polymerization, based on the 2-(3,4,5-trimethoxybenzoyl)-benzo[b]thiophene molecular skeleton with a methoxy substituent at the C-4, C-5, C-6 or C-7 position on the benzene ring, was evaluated for antiproliferative activity against a panel of five cancer cell lines, for inhibition of tubulin polymerization and for cell cycle effects. Replacing the methyl group at the C-3 position resulted in increased activity compared with the corresponding 3-unsubstituted counterpart. The structure-activity relationship established that the best activities were obtained with the methoxy group placed at the C-4, C-6 or C-7 position. Most of these compounds exhibited good growth inhibition activity and arrest K562 cells in the G2-M phase via microtubule depolymerization. ispartof: Bioorganic & Medicinal Chemistry vol:18 issue:14 pages:5114-5122 ispartof: location:England status: published
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- 2010
8. Synthesis and antiproliferative activity of 3-amino-N-phenyl-1H-indazole-1-carboxamides
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Demetrio Raffa, Fiorella Meneghetti, Rosaria Maria Pipitone, Gabriella Bombieri, Stella Cascioferro, Domenico Schillaci, Giuseppe Daidone, Manlio Tolomeo, Antonietta Di Cristina, Stefania Grimaudo, Salvatore Plescia, Benedetta Maggio, Giorgio Gallo, Maria Valeria Raimondi, RAFFA, D, MAGGIO, B, CASCIOFERRO, SM, RAIMONDI, MV, SCHILLACI, D, GALLO, G, DAIDONE, G, PLESCIA, S, MENEGHETTI, F, BOMBIERI, G, DI CRISTINA, A, PIPITONE, RM, GRIMAUDO, S, and TOLOMEO, M
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Indazoles ,Antineoplastic Agents ,Crystallography, X-Ray ,Retinoblastoma Protein ,chemistry.chemical_compound ,Structure-Activity Relationship ,Cell Line, Tumor ,Neoplasms ,Drug Discovery ,medicine ,Humans ,Cell Proliferation ,G0-G1 arrest ,Pharmacology ,Indazole ,Molecular Structure ,Chemistry ,Cell growth ,Melanoma ,Organic Chemistry ,Cell Cycle ,Cancer ,1H-Indazole-1-carboxamides ,Crystallographic study ,pRb ,1H-Indazole-1-carboxamide ,General Medicine ,Cell cycle ,medicine.disease ,Amides ,Settore CHIM/08 - Chimica Farmaceutica ,In vitro ,Crystallographyc study ,Leukemia ,Biochemistry ,Neoplastic cell - Abstract
A series of new 3-amino-N-phenyl-1H-indazole-1-carboxamides 10 have been prepared from commercially available phenyl isocyanate precursors 8 and 3-aminoindazole 9. Some of the synthesized compounds were evaluated for their in vitro antineoplastic activity against 60 human cell lines derived from seven clinically isolated cancer types (lung, colon, melanoma, renal, ovarian, brain, and leukemia) according to the NCI standard protocol. The test results indicated that 3-amino-1H-indazole-1-carboxamides 10 were endowed with an interesting antiproliferative activity. The most active compounds of this series, 10d,e, were able to inhibit cell growth of many neoplastic cell lines at concentrations lower than 1 μM (0.0153 μM in SR leukemia) causing a block in G0–G1 phase of cell cycle. Analysis of pRb expression showed that these two compounds increased the ratio between underphosphorylated pRb and total pRb. The X-ray structure of 10w, confirmed the 3-amino-N-phenyl-1H-indazole-1-carboxamide structure of compounds 10.
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- 2009
9. Design, synthesis and structure-activity relationship of 2-(3',4',5'-trimethoxybenzoyl)-benzo[b]furan derivatives as a novel class of inhibitors of tubulin polymerization
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Stefania Grimaudo, Nicola Zonta, Ernest Hamel, Carlota Lopez Cara, Andrea Brancale, Maria Rosaria Pipitone, Olga Cruz-Lopez, Pier Giovanni Baraldi, Manlio Tolomeo, Maria Dora Carrion, Romeo Romagnoli, Jan Balzarini, Antonietta Di Cristina, Romagnoli, R, Baraldi, PG, Carrion, MD, Cara, CL, Cruz-Lopez, O, Tolomeo, M, Grimaudo, S, Di Cristina, A, Pipitone, RM, Balzarini, J, Zonta, N, Brancale, A, and Hamel, E
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structure-activity ,Stereochemistry ,Clinical Biochemistry ,Pharmaceutical Science ,Antineoplastic Agents ,macromolecular substances ,Biochemistry ,Chemical synthesis ,Article ,Structure-Activity Relationship ,chemistry.chemical_compound ,benzo[b]furans ,Microtubule ,Cell Line, Tumor ,Furan ,Drug Discovery ,Humans ,Structure–activity relationship ,Molecular Biology ,Benzofurans ,Cell Proliferation ,Binding Sites ,Dose-Response Relationship, Drug ,biology ,Chemistry ,Tubulin Modulators ,Cell growth ,Cell Cycle ,Organic Chemistry ,Small molecule ,tubulin polymerization ,Tubulin ,Drug Design ,biology.protein ,Molecular Medicine ,Protein Multimerization ,Colchicine - Abstract
The biological importance of microtubules in mitosis and cell division makes them an interesting target for the development of anticancer agents. Small molecules such as benzo[b]furans are attractive as inhibitors of tubulin polymerization. Thus, a new class of inhibitors of tubulin polymerization based on the 2-(3′,4′,5′-trimethoxybenzoyl)-benzo[b]furan molecular skeleton, with electron-donating (Me, OMe or OH) or electron-withdrawing (F, Cl and Br) substituents on the benzene ring, was synthesized and evaluated for antiproliferative activity, inhibition of tubulin polymerization and cell cycle effects. Adding a methyl group at the C-3 position resulted in increased activity. The most promising compound in this series was 2-(3′,4′,5′-trimethoxybenzoyl)-3-methyl-6-ethoxy-benzo[b]furan, which inhibits cancer cell growth at nanomolar concentrations and interacts strongly with tubulin by binding to the colchicine site.
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- 2009
10. Antiproliferative agents that interfere with the cell cycle at the G(1)-->S transition: further development and characterization of a small library of stilbene-derived compounds
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Stefania Grimaudo, Rosaria Maria Pipitone, Nicola Gebbia, Maurizio Recanatini, Marinella Roberti, Antonietta Di Cristina, Andrea Cavalli, Daniela Pizzirani, Manlio Tolomeo, Pizzirani D., Roberti M., Cavalli A., Grimaudo S., Di Cristina A., Pipitone R.M., Gebbia N., Tolomeo M., Recanatini M., PIZZIRANI D, ROBERTI M, CAVALLI A, GRIMAUDO S, DI CRISTINA A, PIPITONE MR, GEBBIA N, TOLOMEO M, and RECANATINI M
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Stereochemistry ,Cellular differentiation ,Antineoplastic Agents ,Apoptosis ,HL-60 Cells ,Biochemistry ,S Phase ,Small Molecule Libraries ,chemistry.chemical_compound ,Inhibitory Concentration 50 ,Biological profile ,Cell Line, Tumor ,Drug Discovery ,Stilbenes ,pharmacophores ,Humans ,General Pharmacology, Toxicology and Pharmaceutics ,Phosphorylation ,Pharmacology ,Chemistry ,Organic Chemistry ,G1 Phase ,Retinoblastoma ,G1/S transition ,Cell Differentiation ,Cell cycle ,Flow Cytometry ,Combinatorial chemistry ,antitumor agent ,Antiproliferative Agents ,Molecular Medicine ,Triol ,cell cycle ,Pharmacophore ,C-C coupling ,K562 Cells - Abstract
In this continuation of our research on derivatives containing the stilbene privileged structure or that are derived from it, we report the results of further studies carried out on the previously initiated collection of compounds. We used a parallel synthetic approach to rapidly obtain small sets of compounds and started the annotation of the library in progress by calculating some physicochemical properties to be eventually correlated with biological activities. A pharmacophore for the antiproliferative activity was also built to summarize the features of the library. We evaluated the antiproliferative and pro-apoptotic activities of all compounds as well as the cell-cycle effects of some representative compounds. After in-depth investigations, 3'-phenyl- [1, 1';4', 1"]terphenyl-4,3",5"-triol showed the most interesting biological profile, as it interferes with cell-cycle progression at the G(1) -> S transition, acting on retinoblastoma phosphorylation and inducing cell differentiation.
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- 2008
11. Novel Terphenyls and 3,5-Diaryl Isoxazole Derivatives Endowed with Growth Supporting and Antiapoptotic Properties
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Stefania Grimaudo, Giuseppina Grisolia, Antonietta Di Cristina, Daniele Simoni, Riccardo Rondanin, Marco Eleopra, Michele Rizzi, Maria Rosaria Pipitone, Maria Rita Bongiorno, Riccardo Baruchello, Manlio Tolomeo, Mario Arico, Francesco Paolo Invidiata, SIMONI, D, RONDANIN, R, BARUCHELLO, R, RIZZI, M, GRISOLIA, G, ELEOPRA, M, GRIMAUDO S, DI CRISTINA, A, PIPITONE, MR, BONGIORNO, MR, ARICO', M, INVIDIATA, FP, and TOLOMEO, M
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chemistry.chemical_classification ,Molecular Structure ,Stereochemistry ,Nitro compound ,Apoptosis ,Biological activity ,Isoxazoles ,Chemical synthesis ,Antiapoptotic Agent ,Structure-Activity Relationship ,chemistry.chemical_compound ,chemistry ,Cell Line, Tumor ,Terphenyl Compounds ,Terphenyl ,Drug Discovery ,Nitro ,Humans ,Molecular Medicine ,Moiety ,Isoxazole - Abstract
A new study on terphenyl and diaryl-isoxazole and -isoxazoline derivatives, maintaining a common 3-adamantyl-4-hydroxyphenyl moiety, has been conducted to find compounds with growth supporting and antiapoptotic properties. Unexpectedly, diphenyisoxazole derivatives bearing a nitro group replacing the carboxylic function have been found with the highest cell protective activity within the series, in complete and in serum-free conditions. Inhibition of apoptosis induced by daunorubicin has also been observed for the most active compound.
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- 2008
12. Synthesis and Biological Evaluation of 2-Amino-3-(3’,4’,5’-Trimethoxybenzoyl)-6-Substituted-4,5,6,7-Tetrahydrothieno[2,3-c]pyridine Derivatives as Antimitotic Agents and Inhibitors of Tubulin Polymerization
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Antonietta Di Cristina, Maria Rosa Pipitone, Pier Giovanni Baraldi, Ernest Hamel, Taradas Sarkar, Stefania Grimaudo, Andrea Brancale, Olga Cruz-Lopez, Jan Balzarini, Carlota Lopez Cara, Manlio Tolomeo, Maria Dora Carrion, Romeo Romagnoli, Sahar Kandil, ROMAGNOLI R, BARALDI PG, CARRION MD, CRUZ-LOPEZ O, CARA CL, TOLOMEO M, GRIMAUDO S, Di CRISTINA, A, PIPITONE, RM, BALZARINI J, KANDIL S, BRANCALE A, SARKAR T, and HAMEL E
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Pyridines ,Stereochemistry ,Clinical Biochemistry ,Pharmaceutical Science ,Antimitotic Agents ,Crystallography, X-Ray ,Biochemistry ,Chemical synthesis ,Article ,Inhibitory Concentration 50 ,Structure-Activity Relationship ,chemistry.chemical_compound ,Tubulin ,Microtubule ,Drug Discovery ,Pyridine ,Animals ,Structure–activity relationship ,Cytotoxicity ,Molecular Biology ,Molecular Structure ,biology ,Bicyclic molecule ,Chemistry ,Organic Chemistry ,biology.protein ,Molecular Medicine ,Antimitotic Agent - Abstract
Microtubules are among the most successful targets of compounds potentially useful for cancer therapy. A new series of inhibitors of tubulin polymerization based on the 2-amino-3-(3,4,5-trimethoxybenzoyl)-4,5,6,7-tetrahydrothieno[b]pyridine molecular skeleton was synthesized and evaluated for antiproliferative activity, inhibition of tubulin polymerization, and cell cycle effects. The most promising compound in this series was 2-amino-3-(3,4,5-trimethoxybenzoyl)-6-methoxycarbonyl-4,5,6,7-tetrahydrothieno[b]pyridine, which inhibits cancer cell growth with IC(50)-values ranging from 25 to 90 nM against a panel of four cancer cell lines, and interacts strongly with tubulin by binding to the colchicine site. In this series of N(6)-carbamate derivatives, any further increase in the length and in the size of the alkyl chain resulted in reduced activity.
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- 2008
13. Stilbene-based anticancer agents: Resveratrol analogues active toward HL60 leukemic cells wit a non-specific phase mechanism
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Nicola Gebbia, Antonietta Di Cristina, Riccardo Baruchello, Enrico Aiello, Francesco Dieli, Marco Eleopra, Paolo Marchetti, Francesco Paolo Invidiata, Marinella Roberti, Lucia Crosta, Manlio Tolomeo, Daniele Simoni, Stefania Grimaudo, Stefania Aiello, Simoni D., Roberti M., Invidiata F. P., Aiello E., Aiello S., Marchetti P., Baruchello R., Eleopra M., Di Cristina A., Grimaudo S., Gebbia N., Crosta L., Dieli F., Tolomeo M., SIMONI, D, ROBERTI, M, INVIDIATA, F, AIELLO, E, AIELLO, S, MARCHETTI, P, BARUCHELLO, R, ELEOPRA, M, DI CRISTINA, A, GRIMAUDO, S, GEBBIA, N, CROSTA, L, DIELI, F, and TOLOMEO, M
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Antimony ,HL60 ,Clinical Biochemistry ,Pharmaceutical Science ,Antineoplastic Agents ,HL-60 Cells ,Resveratrol ,Biochemistry ,Structure-Activity Relationship ,chemistry.chemical_compound ,Stilbenes ,Drug Discovery ,medicine ,Humans ,Structure–activity relationship ,Molecular Biology ,S phase ,Cell Proliferation ,Molecular Structure ,Organic Chemistry ,Cell cycle ,Mechanism of action ,chemistry ,Anticancer agent ,Cell culture ,Apoptosis ,Resveratrol analogue ,Cell cycle analysis ,Molecular Medicine ,medicine.symptom - Abstract
Several stilbenes, related to known resveratrol, have been synthesized and tested for their anticancer effect on HL60 leukemia cell line, taking particular care of the cell cycle analysis. The most potent compound was the known (Z)-3,4',5-trimethoxystilbene (6b) which was active as apoptotic agent at 0.24 microM. Differently from other stilbenes (including resveratrol) that induced a prevalent recruitment of cells in S phase of cell cycle, we found a peculiar behavior of 6b that caused a decrease of cells in all phases of cell cycle (G0-G1, S, and G2-M) and a proportional increase of apoptotic cells. The potent pro-apoptotic activity shown by compound 6b and its effects on cell cycle make this compound of great interest for further investigations.
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- 2006
14. Studies on the apoptotic activity of natural and synthetic retinoids: discovery of a new class of synthetic terphenyls that potently support cell growth and inhibit apoptosis in neuronal and HL-60 cells
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Manlio Tolomeo, Stefania Grimaudo, Giuseppina Grisolia, Riccardo Baruchello, Sabrina Cavallini, Daniele Simoni, and Antonietta Di Cristina, Vincenzo Abbadessa, Francesco Paolo Invidiata, Nicola Gebbia, Riccardo Rondanin, Anna Siniscalchi, Marinella Roberti, Silvia Marino, Lucia Crosta, Giuseppe Giannini, Marcello Rossi, Stefania Aiello, Simoni D., Giannini G., Roberti M., Rondanin R., Baruchello R., Rossi M., Grisolia G., Invidiata F. P., Aiello S., Marino S., Cavallini S., Siniscalchi A., Gebbia N., Crosta L., Grimaudo S., Abbadessa V., Di Cristina A., Tolomeo M., SIMONI D, GIANNINI G, ROBERTI M, RONDANIN R, BARUCHELLO R, ROSSI M, GRISOLIA G, INVIDIATA FP, AIELLO S, MARINO S, CAVALLINI S, SINISCALCHI A, GEBBIA N, CROSTA L, GRIMAUDO S, ABBADESSA V, DI CRISTINA A, and TOLOMEO M
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Programmed cell death ,Necrosis ,receptor-alpha ,medicine.drug_class ,mechanism ,Apoptosis ,HL-60 Cells ,necrosis ,chemistry.chemical_compound ,Retinoids ,death ,Terphenyl ,Drug Discovery ,medicine ,Humans ,Retinoid ,Neurons ,Cell growth ,biphenyl-4-carboxylic acid ,arotinoid ,In vitro ,Cell biology ,Cultured cortical-neuron ,chemistry ,Biochemistry ,Cell culture ,retinobenzoic acid ,Molecular Medicine ,Indicators and Reagents ,multidrug ,medicine.symptom ,Cell Division ,(14R)-14-hydroxy-4,14-retro-retinol - Abstract
New terphenyl derivatives have been synthesized and tested for their effect on cell survival in serum-free cultures. These compounds protected HL60 cells from death and supported their growth with an activity higher than that of the natural 14-hydroxy-retro-retinol. Terphenyls 26 and 28 also possess antiapoptotic activity on neuronal cells, proving them as possible candidates for the treatment of neurodegenerative and ischemic diseases.
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- 2005
15. Heterocyclic and Phenyl Double-Bond-Locked Combretastatin Analogues Possessing Potent Apoptosis-inducing activity in HL60 and in MDR Cell lines
- Author
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Nicola Gebbia, Maria Meli, Antonietta Di Cristina, M. Katherine Jung, Daniele Simoni, Francesco Paolo Invidiata, Luisa Dusonchet, Stefania Grimaudo, Lucia Crosta, Marinella Roberti, Laura Piccagli, Ernest Hamel, Giuseppina Grisolia, Riccardo Rondanin, Giuseppe Giannini, Marcello Rossi, Manlio Tolomeo, Vincenzo Abbadessa, Riccardo Baruchello, Romeo Simgma-Tau Ind. Farm. Riunite Spa Romagnoli, SIMONI D, GRISOLIA G, GIANNINI G, ROBERTI M, RONDANIN R, PICCAGLI L, BARUCHELLO R, ROSSI M, ROMAGNOLI R, INVIDIATA FP, GRIMAUDO S, JUNG MK, HAMEL E, GEBBIA N, CROSTA L, ABBADESSA V, DI CRISTINA A, DUSONCHET L, MELI M, TOLOMEO M, Simoni D., Grisolia G., Giannini G., Roberti M., Rondanin R., Piccagli L., Baruchello R., Rossi M., Romagnoli R., Invidiata F. P., Grimaudo S., Jung M. K., Hamel E., Gebbia N., Crosta O. L., Abbadessa. O. V., Di Cristina A., Dusonchet L., Meli M., and Tolomeo M.
- Subjects
Models, Molecular ,A-4 ANALOGS ,Double bond ,HL60 ,Stereochemistry ,Pyridines ,TUBULIN ,Apoptosis ,ANTINEOPLASTIC AGENTS ,chemistry.chemical_compound ,Structure-Activity Relationship ,Cell Line, Tumor ,Drug Discovery ,Stilbenes ,Benzene Derivatives ,Humans ,Isoxazole ,BIOLOGICAL EVALUATION ,Cytotoxicity ,chemistry.chemical_classification ,Combretastatin ,biology ,COLCHICINE ,DEATH ,Isoxazoles ,Drug Resistance, Multiple ,Tubulin ,ANTIMITOTIC ANTITUMOR AGENTS ,MULTIDRUG ,chemistry ,Cell culture ,Drug Resistance, Neoplasm ,DISCOVERY ,biology.protein ,Molecular Medicine ,Drug Screening Assays, Antitumor ,SOLID TUMOR-THERAPY - Abstract
Two new series of combretastatin (CA-4) analogues have been prepared. The alkenyl motif of CA-4 was replaced either by a five-membered heterocyclic (isoxazoline or isoxazole) or by a six-membered ring (pyridine or benzene). The new compounds have been evaluated for their effects on tubulin assembly and for cytotoxic and apoptotic activities. Five compounds (18b, 20a, 21a, 34b, and 35b) demonstrated an attractive profile of cytotoxicity (IC501 microM) and apoptosis-inducing activity but poor antitubulin activity. The isoxazoline derivatives 18b, 20a, and 21a, demonstrated potent apoptotic activity different from that of natural CA-4. Their ability to block most cells in the G2 phase suggests that these compounds could act on targets different from the mitotic spindle. This would indicate activation of both the intrinsic and the extrinsic apoptotic pathways. The data suggest unambiguously that structural alteration of the stilbene motif of CA-4 can be extremely effective in producing potent apoptosis-inducing agents.
- Published
- 2005
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