1. Chromenone derivatives as a versatile scaffold with dual mode of inhibition of HIV-1 reverse transcriptase-associated Ribonuclease H function and integrase activity.
- Author
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Esposito F, Ambrosio FA, Maleddu R, Costa G, Rocca R, Maccioni E, Catalano R, Romeo I, Eleftheriou P, Karia DC, Tsirides P, Godvani N, Pandya H, Corona A, Alcaro S, Artese A, Geronikaki A, and Tramontano E
- Subjects
- Anti-HIV Agents chemical synthesis, Anti-HIV Agents chemistry, Coumarins chemical synthesis, Coumarins chemistry, Dose-Response Relationship, Drug, HIV Integrase Inhibitors chemical synthesis, HIV Integrase Inhibitors chemistry, HIV-1 enzymology, Microbial Sensitivity Tests, Molecular Structure, Reverse Transcriptase Inhibitors chemical synthesis, Reverse Transcriptase Inhibitors chemistry, Ribonuclease H, Human Immunodeficiency Virus metabolism, Structure-Activity Relationship, Anti-HIV Agents pharmacology, Coumarins pharmacology, HIV Integrase Inhibitors pharmacology, HIV-1 drug effects, Reverse Transcriptase Inhibitors pharmacology, Ribonuclease H, Human Immunodeficiency Virus antagonists & inhibitors
- Abstract
A number of compounds targeting different processes of the Human Immunodeficiency Virus type 1 (HIV-1) life cycle have been developed in the continuing fight against AIDS. Coumarin-based molecules already proved to act as HIV-1 Protease (PR) or Integrase (IN) inhibitors and also to target HIV-1 reverse transcriptase (RT), blocking the DNA-dependent DNA-polymerase activity or the RNA-dependent DNA-polymerase activity working as common NNRTIs. In the present study, with the aim to exploit a coumarin-based scaffold to achieve the inhibition of multiple viral coded enzymatic functions, novel 4-hydroxy-2H, 5H-pyrano (3, 2-c) chromene-2, 5-dione derivatives were synthesized. The modeling studies calculated the theoretical binding affinity of the synthesized compounds on both HIV-1 IN and RT-associated Ribonuclease H (RNase H) active sites, which was confirmed by biological assays. Our results provide a basis for the identification of dual HIV-1 IN and RT RNase H inhibitors compounds., (Copyright © 2019 Elsevier Masson SAS. All rights reserved.)
- Published
- 2019
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