1. Synthesis and evaluation of coumarin derivatives as potential dual-action HIV-1 protease and reverse transcriptase inhibitors.
- Author
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Olomola TO, Klein R, Mautsa N, Sayed Y, and Kaye PT
- Subjects
- Coumarins chemical synthesis, HIV Infections drug therapy, HIV Infections virology, HIV Protease metabolism, HIV Protease Inhibitors chemical synthesis, HIV Reverse Transcriptase metabolism, HIV-1 drug effects, Humans, Models, Molecular, Reverse Transcriptase Inhibitors chemical synthesis, Zidovudine chemical synthesis, Zidovudine chemistry, Zidovudine pharmacology, Coumarins chemistry, Coumarins pharmacology, HIV Protease Inhibitors chemistry, HIV Protease Inhibitors pharmacology, HIV Reverse Transcriptase antagonists & inhibitors, HIV-1 enzymology, Reverse Transcriptase Inhibitors chemistry, Reverse Transcriptase Inhibitors pharmacology
- Abstract
Baylis-Hillman-derived 3-(benzylaminomethyl)coumarins have been treated, sequentially, with chloroacetyl chloride and propargylamine to afford alkynylated coumarins as substrates for Click Chemistry reactions with azidothymidine (AZT) in the presence of a Cu(I) catalyst. The dual-action HIV-1 protease (PR) and reverse transcriptase (RT) inhibition potential of the resulting N-benzylated cycloaddition products, and a series of non-benzylated analogues, has been explored using saturation transfer difference (STD) NMR, computer modelling and enzyme inhibition techniques., (Copyright © 2013 Elsevier Ltd. All rights reserved.)
- Published
- 2013
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