(3Z)-3-(2-[4-(aryl)-1,3-thiazol-2-yl]hydrazin-1-ylidene)-2,3-dihydro- 1H -indol-2-one derivatives as dual inhibitors of HIV-1 reverse transcriptase

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

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31 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)452-460
Number of pages9
JournalEuropean Journal of Medicinal Chemistry
Volume93
DOIs
Publication statusPublished - Mar 26 2015

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Keywords

  • (3Z)-3-(2-[4-(aryl)-1,3-thiazol-2-yl]
  • Antiviral agents
  • HIV-1
  • HIV-1 RT dual inhibitors
  • Molecular modelling
  • RNase H
  • hydrazin-1-ylidene)-2,3-dihydro-1H-indol-2-ones

ASJC Scopus subject areas

  • Pharmacology
  • Drug Discovery
  • Organic Chemistry

Cite this

Meleddu, R., Distinto, S., Corona, A., Bianco, G., Cannas, V., Esposito, F., Artese, A., Alcaro, S., Matyus, P., Bogdan, D., Cottiglia, F., Tramontano, E., & Maccioni, E. (2015). (3Z)-3-(2-[4-(aryl)-1,3-thiazol-2-yl]hydrazin-1-ylidene)-2,3-dihydro- 1H -indol-2-one derivatives as dual inhibitors of HIV-1 reverse transcriptase. European Journal of Medicinal Chemistry, 93, 452-460. https://doi.org/10.1016/j.ejmech.2015.02.032