Abstract |
The HIV-1 Reverse Transcriptase (RT) is a validated and deeply explored biological target for the treatment of AIDS. However, only drugs targeting the RT-associated DNA polymerase (DP) function have been approved for clinical use. We designed and synthesised a new generation of HIV-1 RT inhibitors, based on the (3Z)-3-(2-[4-(aryl)-1,3-thiazol-2-yl]hydrazin-1-ylidene)-2,3-dihydro-1H-indol-2-one scaffold. These compounds are active towards both RT-associated functions, DNA polymerase and ribonuclease H. The structure, biological activity and mode of action of the new derivatives have been investigated. In particular, the nature of the aromatic group in the position 4 of the thiazole ring plays a key role in the modulation of the activity towards the two RT-associated functions.
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Authors | Rita Meleddu, Simona Distinto, Angela Corona, Giulia Bianco, Valeria Cannas, Francesca Esposito, Anna Artese, Stefano Alcaro, Peter Matyus, Dora Bogdan, Filippo Cottiglia, Enzo Tramontano, Elias Maccioni |
Journal | European journal of medicinal chemistry
(Eur J Med Chem)
Vol. 93
Pg. 452-60
(Mar 26 2015)
ISSN: 1768-3254 [Electronic] France |
PMID | 25728026
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2015 Elsevier Masson SAS. All rights reserved. |
Chemical References |
- Indoles
- Reverse Transcriptase Inhibitors
- Thiazoles
- reverse transcriptase, Human immunodeficiency virus 1
- HIV Reverse Transcriptase
- DNA-Directed DNA Polymerase
- Ribonuclease H
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Topics |
- DNA-Directed DNA Polymerase
(metabolism)
- Drug Design
- HIV Reverse Transcriptase
(antagonists & inhibitors, chemistry, metabolism)
- HIV-1
(enzymology)
- Indoles
(chemical synthesis, chemistry, metabolism, pharmacology)
- Models, Molecular
- Molecular Docking Simulation
- Protein Conformation
- Reverse Transcriptase Inhibitors
(chemical synthesis, chemistry, metabolism, pharmacology)
- Ribonuclease H
(antagonists & inhibitors)
- Structure-Activity Relationship
- Thiazoles
(chemistry)
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