A versatile and practical synthesis toward the development of novel HIV-1 integrase inhibitors
| Autor: | Giulia Vignaroli, Encarna Gonzalo, Zeger Debyser, Silvio Massa, Cristina Tintori, Maurizio Botta, José A. Esté, Frauke Christ, Marta Rinaldi, Anna Innitzer, Luigi Franchi |
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| Jazyk: | angličtina |
| Rok vydání: | 2011 |
| Předmět: |
Models
Molecular Spectrometry Mass Electrospray Ionization Magnetic Resonance Spectroscopy Drug Evaluation Preclinical Integrase inhibitor HIV Integrase 01 natural sciences Biochemistry Cell Line 03 medical and health sciences antiviral agents inhibitors Drug Discovery medicine Humans HIV Integrase Inhibitors General Pharmacology Toxicology and Pharmaceutics 030304 developmental biology Pharmacology 0303 health sciences biology HIV integrase 010405 organic chemistry Organic Chemistry Raltegravir Combinatorial chemistry 0104 chemical sciences 3. Good health Integrase DNA binding site Viral replication Cell culture Docking (molecular) biology.protein Hiv 1 integrase Molecular Medicine medicine.drug |
| Zdroj: | ChemMedChem; Vol 6 ChemMedChem |
| ISSN: | 1860-7179 |
| DOI: | 10.1002/cmdc.201000510 |
| Popis: | As a continuation of our previous work, which resulted in the identification of a new hit compound as an HIV-1 integrase inhibitor, three novel series of salicylic acid derivatives were synthesized using three versatile and practical synthetic strategies and were assayed for their capacity to inhibit the catalytic activity of HIV-1 integrase. Biological evaluations revealed that some of the synthesized compounds possess good inhibitory potency in enzymatic assays and are able to inhibit viral replication in MT-4 cells at low micromolar concentrations. Finally, docking studies were conducted to analyze the binding mode of the synthesized compounds within the DNA binding site of integrase in order to refine their structure-activity relationships. |
| Databáze: | OpenAIRE |
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