Search

Your search keyword '"Poli, Giulio"' showing total 8 results
Start Over Author "Poli, Giulio" Journal journal of medicinal chemistry
8 results on '"Poli, Giulio"'

1. Targeting Acute Myelogenous Leukemia Using Potent Human Dihydroorotate Dehydrogenase Inhibitors Based on the 2-Hydroxypyrazolo[1,5-a]pyridine Scaffold: SAR of the Aryloxyaryl Moiety

Author

Sainas, Stefano, primary, Giorgis, Marta, additional, Circosta, Paola, additional, Poli, Giulio, additional, Alberti, Marta, additional, Passoni, Alice, additional, Gaidano, Valentina, additional, Pippione, Agnese C., additional, Vitale, Nicoletta, additional, Bonanni, Davide, additional, Rolando, Barbara, additional, Cignetti, Alessandro, additional, Ramondetti, Cristina, additional, Lanno, Alessia, additional, Ferraris, Davide M., additional, Canepa, Barbara, additional, Buccinnà, Barbara, additional, Piccinini, Marco, additional, Rizzi, Menico, additional, Saglio, Giuseppe, additional, Al-Karadaghi, Salam, additional, Boschi, Donatella, additional, Miggiano, Riccardo, additional, Tuccinardi, Tiziano, additional, and Lolli, Marco L., additional

Published
2022
Full Text
View/download PDF

2. Reversible Monoacylglycerol Lipase Inhibitors: Discovery of a New Class of Benzylpiperidine Derivatives

Author

Bononi, Giulia, primary, Di Stefano, Miriana, additional, Poli, Giulio, additional, Ortore, Gabriella, additional, Meier, Philip, additional, Masetto, Francesca, additional, Caligiuri, Isabella, additional, Rizzolio, Flavio, additional, Macchia, Marco, additional, Chicca, Andrea, additional, Avan, Amir, additional, Giovannetti, Elisa, additional, Vagaggini, Chiara, additional, Brai, Annalaura, additional, Dreassi, Elena, additional, Valoti, Massimo, additional, Minutolo, Filippo, additional, Granchi, Carlotta, additional, Gertsch, Jürg, additional, and Tuccinardi, Tiziano, additional

Published
2022
Full Text
View/download PDF

3. Shedding X-ray Light on the Role of Magnesium in the Activity of Mycobacterium tuberculosis Salicylate Synthase (MbtI) for Drug Design

Author

Mori, Matteo, primary, Stelitano, Giovanni, additional, Gelain, Arianna, additional, Pini, Elena, additional, Chiarelli, Laurent R., additional, Sammartino, José C., additional, Poli, Giulio, additional, Tuccinardi, Tiziano, additional, Beretta, Giangiacomo, additional, Porta, Alessio, additional, Bellinzoni, Marco, additional, Villa, Stefania, additional, and Meneghetti, Fiorella, additional

Published
2020
Full Text
View/download PDF

4. 1,3-Dipolar Cycloaddition, HPLC Enantioseparation, and Docking Studies of Saccharin/Isoxazole and Saccharin/Isoxazoline Derivatives as Selective Carbonic Anhydrase IX and XII Inhibitors

Author

D’Ascenzio, Melissa, primary, Secci, Daniela, additional, Carradori, Simone, additional, Zara, Susi, additional, Guglielmi, Paolo, additional, Cirilli, Roberto, additional, Pierini, Marco, additional, Poli, Giulio, additional, Tuccinardi, Tiziano, additional, Angeli, Andrea, additional, and Supuran, Claudiu T., additional

Published
2020
Full Text
View/download PDF

5. Optimization of a Benzoylpiperidine Class Identifies a Highly Potent and Selective Reversible Monoacylglycerol Lipase (MAGL) Inhibitor

Author

Granchi, Carlotta, primary, Lapillo, Margherita, additional, Glasmacher, Sandra, additional, Bononi, Giulia, additional, Licari, Cristina, additional, Poli, Giulio, additional, el Boustani, Maguie, additional, Caligiuri, Isabella, additional, Rizzolio, Flavio, additional, Gertsch, Jürg, additional, Macchia, Marco, additional, Minutolo, Filippo, additional, Tuccinardi, Tiziano, additional, and Chicca, Andrea, additional

Published
2019
Full Text
View/download PDF

6. Shedding X-ray Light on the Role of Magnesium in the Activity of Mycobacterium tuberculosisSalicylate Synthase (MbtI) for Drug Design

Author

Mori, Matteo, Stelitano, Giovanni, Gelain, Arianna, Pini, Elena, Chiarelli, Laurent R., Sammartino, José C., Poli, Giulio, Tuccinardi, Tiziano, Beretta, Giangiacomo, Porta, Alessio, Bellinzoni, Marco, Villa, Stefania, and Meneghetti, Fiorella

Abstract

The Mg2+-dependent Mycobacterium tuberculosissalicylate synthase (MbtI) is a key enzyme involved in the biosynthesis of siderophores. Because iron is essential for the survival and pathogenicity of the microorganism, this protein constitutes an attractive target for antitubercular therapy, also considering the absence of homologous enzymes in mammals. An extension of the structure–activity relationships of our furan-based candidates allowed us to disclose the most potent competitive inhibitor known to date (10, Ki= 4 μM), which also proved effective on mycobacterial cultures. By structural studies, we characterized its unexpected Mg2+-independent binding mode. We also investigated the role of the Mg2+cofactor in catalysis, analyzing the first crystal structure of the MbtI–Mg2+–salicylate ternary complex. Overall, these results pave the way for the development of novel antituberculars through the rational design of improved MbtI inhibitors.

Published
2020
Full Text
View/download PDF

7. Targeting Acute Myelogenous Leukemia Using Potent Human Dihydroorotate Dehydrogenase Inhibitors Based on the 2-Hydroxypyrazolo[1,5- a ]pyridine Scaffold: SAR of the Aryloxyaryl Moiety.

Author

Sainas S, Giorgis M, Circosta P, Poli G, Alberti M, Passoni A, Gaidano V, Pippione AC, Vitale N, Bonanni D, Rolando B, Cignetti A, Ramondetti C, Lanno A, Ferraris DM, Canepa B, Buccinnà B, Piccinini M, Rizzi M, Saglio G, Al-Karadaghi S, Boschi D, Miggiano R, Tuccinardi T, and Lolli ML

Subjects
Animals, Humans, Mice, Antiviral Agents pharmacology, Dihydroorotate Dehydrogenase, Dipyridamole therapeutic use, Enzyme Inhibitors chemistry, Enzyme Inhibitors pharmacology, Enzyme Inhibitors therapeutic use, Pyridines pharmacology, Pyridines therapeutic use, Structure-Activity Relationship, Leukemia, Myeloid, Acute drug therapy, Oxidoreductases Acting on CH-CH Group Donors
Abstract

In recent years, human dihydroorotate dehydrogenase inhibitors have been associated with acute myelogenous leukemia as well as studied as potent host targeting antivirals. Starting from MEDS433 (IC 50 1.2 nM), we kept improving the structure-activity relationship of this class of compounds characterized by 2-hydroxypyrazolo[1,5- a ]pyridine scaffold. Using an in silico/crystallography supported design, we identified compound 4 (IC 50 7.2 nM), characterized by the presence of a decorated aryloxyaryl moiety that replaced the biphenyl scaffold, with potent inhibition and pro-differentiating abilities on AML THP1 cells (EC 50 74 nM), superior to those of brequinar (EC 50 249 nM) and boosted when in combination with dipyridamole. Finally, compound 4 has an extremely low cytotoxicity on non-AML cells as well as MEDS433; it has shown a significant antileukemic activity in vivo in a xenograft mouse model of AML.

Published
2022
Full Text
View/download PDF

8. 1,3-Dipolar Cycloaddition, HPLC Enantioseparation, and Docking Studies of Saccharin/Isoxazole and Saccharin/Isoxazoline Derivatives as Selective Carbonic Anhydrase IX and XII Inhibitors.

Author

D'Ascenzio M, Secci D, Carradori S, Zara S, Guglielmi P, Cirilli R, Pierini M, Poli G, Tuccinardi T, Angeli A, and Supuran CT

Subjects
Antineoplastic Agents chemical synthesis, Antineoplastic Agents chemistry, Antineoplastic Agents pharmacology, Carbonic Anhydrase IX antagonists & inhibitors, Carbonic Anhydrase Inhibitors chemical synthesis, Cell Line, Cycloaddition Reaction, Humans, Isoxazoles chemical synthesis, Isoxazoles chemistry, Isoxazoles pharmacology, MCF-7 Cells, Molecular Docking Simulation, Neoplasms drug therapy, Neoplasms enzymology, Neoplasms metabolism, Saccharin chemical synthesis, Antigens, Neoplasm metabolism, Carbonic Anhydrase IX metabolism, Carbonic Anhydrase Inhibitors chemistry, Carbonic Anhydrase Inhibitors pharmacology, Carbonic Anhydrases metabolism, Saccharin chemistry, Saccharin pharmacology
Abstract

Two series of saccharin/isoxazole and saccharin/isoxazoline hybrids were synthesized by 1,3-dipolar cycloaddition. The new compounds showed to be endowed with potent and selective inhibitory activity against the cancer-related human carbonic anhydrase (hCA) IX and XII isoforms in the nanomolar range, while no affinity was encountered for off-targets, such as hCA I and II. Successive enantioseparation on a milligram scale of the most representative compounds led to the discovery that (S)-isomers were more potent than their corresponding (R)-enantiomers. Lastly, molecular modeling studies were conducted to define those structural requirements that were responsible for the discrimination among selected human isoforms of carbonic anhydrases. Two nanomolar hCA IX and XII inhibitors were also screened for their selective toxicity against non tumoral primary cells (fibroblasts) and against a breast adenocarcinoma cell line (MCF7) in hypoxic environment. The efficacious combination of these compounds with doxorubicin on MCF7 cells was demonstrated after 72 h of treatment.

Published
2020
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results