Towards new C6-rigid S-DABO HIV-1 reverse transcriptase inhibitors: Synthesis, biological investigation and molecular modeling studies
| Autor: | Wen-Xue Chen, Zi-Hong Yan, Jan Balzarini, Christophe Pannecouque, Fen-Er Chen, Hai-Qiu Wu, Erik De Clercq, Qiu-Qin He, Dirk Daelemans |
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| Rok vydání: | 2013 |
| Předmět: |
Molecular model
Pyrimidine Stereochemistry Clinical Biochemistry Mutant Human immunodeficiency virus (HIV) Pharmaceutical Science Pyrimidinones medicine.disease_cause Biochemistry Structure-Activity Relationship chemistry.chemical_compound Drug Discovery medicine Humans Molecular Biology Binding Sites Organic Chemistry virus diseases HIV Reverse Transcriptase Reverse transcriptase Protein Structure Tertiary Molecular Docking Simulation Pyrimidines chemistry Cell culture Docking (molecular) HIV-1 Reverse Transcriptase Inhibitors Molecular Medicine Selectivity Protein Binding |
| Zdroj: | Bioorganic & Medicinal Chemistry. 21:6477-6483 |
| ISSN: | 0968-0896 |
| DOI: | 10.1016/j.bmc.2013.08.040 |
| Popis: | A series of C6-rigid S-DABO analogs characterized by a substituted benzoyl group at C6 position of the pyrimidine ring has been synthesized and biological evaluation as NNRTIs against wild-type HIV-1 strain IIIB, double RT mutant (K103N + Y181C) strain RES056 as well as HIV-2 strain ROD in MT-4 cell cultures. Most of the compounds exhibited moderate antiviral activities. Among them, compound 7q displayed the highest anti-HIV-1 activity with an EC50 value of 0.26 μM and a selectivity index (SI) of 541. The preliminary structure–activity relationship (SAR) of these new S-DABOs was investigated, the target RT was confirmed and docking study was performed. |
| Databáze: | OpenAIRE |
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