Synthesis, cytotoxicity and antiviral evaluation of new series of imidazo[4,5-g]quinoline and pyrido[2,3-g]quinoxalinone derivatives
| Autor: | Irene Briguglio, Erik Laurini, Gabriele Giliberti, Paolo La Colla, Maurizio Fermeglia, Sandra Piras, Roberta Loddo, Pamela Farci, Paolo Giunchedi, Paola Corona, Antonio Carta, Giuseppina Sanna, Elisabetta Gavini, Cristina Ibba, Sabrina Pricl |
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| Přispěvatelé: | Briguglio, Irene, Loddo, Roberta, Laurini, Erik, Fermeglia, Maurizio, Piras, Sandra, Corona, Paola, Giunchedi, Paolo, Gavini, Elisabetta, Sanna, Giuseppina, Giliberti, Gabriele, Ibba, Cristina, Farci, Pamela, La Colla, Paolo, Pricl, Sabrina, Carta, Antonio |
| Rok vydání: | 2014 |
| Předmět: |
RNA viruses
Stereochemistry Pyridines Microbial Sensitivity Tests Pyrido[2 Antiviral Agents chemistry.chemical_compound Structure-Activity Relationship 3-g]quinoxalines Imidazo[4 5-g]quinoline Quinoxalines Antiviral activity DNA viruses Imidazo[4 5-g]quinolines Pyrido[2 3-g]quinoxalines Drug Discovery Structure–activity relationship Humans RNA Viruses Cytotoxicity Imidazo[4 Subgenomic mRNA Pharmacology biology Dose-Response Relationship Drug Molecular Structure Drug discovery Organic Chemistry Quinoline DNA Viruses Imidazoles RNA DNA virus RNA virus Pyrido[2 3-g]quinoxaline General Medicine 5-g]quinolines biology.organism_classification chemistry Quinolines DNA viruse |
| Zdroj: | European journal of medicinal chemistry. 105 |
| ISSN: | 1768-3254 |
| Popis: | Linear aromatic N-tricyclic compounds with promising antiviral activity and minimal cytotoxicity were prepared and analyzed in the last years. Specifically, the pyrido[2,3-g]quinoxalinone nucleus was found endowed with high potency against several pathogenic RNA viruses as etiological agents of important veterinary and human pathologies. Following our research program on new antiviral agents we have designed, synthesized and assayed new series of imidazo[4,5-g]quinoline and pyrido[2,3-g]quinoxalinone derivatives. Lead compounds 1-4 were further modified to enhance their antiviral activity and reduce their cytotoxicity. Thus, different substituents were introduced on N atom at position 1 or the O atom at position 2 of the leads; contextually, several groups were inserted on the nitrogen atom at position 7 of diaminoquinoline intermediates. Title compounds were tested in cell-based assays for cytotoxicity and antiviral activity against RNA virus families containing single-stranded (either positive-sense (ssRNA+) or negative-sense (ssRNA-)), and double-stranded genomes (dsRNA), and against two representatives of DNA virus families. Some derivatives emerged as potential leads for further development as antiviral agents against some viruses of public health significance, such as RSV, Reo, BVDV and HCV. Particularly, compounds 4, 11b, 11c, 13c, 15a, 18 and 21 resulted active against BVDV at concentrations ranging from 1.3 to 5 μM. Compound 21 was also evaluated for its activity on the BVDV RdRp. Compound 4 was also tested as potential anti-HCV compound in a subgenomic replication assay. Molecular simulation results provided a molecular rationale for the anti-BVDV activity of these compounds. |
| Databáze: | OpenAIRE |
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