Synthesis and anti-HIV properties of novel 6-phenylselenenyl-5-propyluracils

• Authors: Agnieszka Miazga , Krzysztof Felczak , Maria A Siwecka , Andrzej Lipniacki , Andrzej Piasek , Tadeusz Kulikowski
• Languages of publication: EN

Abstracts

EN

Novel 6-phenylselenenyl-5-propyluracils were synthesized from 5-propyluracil with the use of regioselective synthesis to give 1-[(2-hydroxyethoxy)-methyl]-6-phenylselenenyl-5-propyluracil (6), 1-ethoxymethyl-6-phenylselenenyl-5-propyluracil (9) and 1-benzyloxymethyl-6-phenylselenenyl-5-propyluracil (10). Interaction of these compounds with recombinant HIV-1 reverse transcriptase (RT) was evaluated using a non-isotopic colorimetric method. Compounds 9 and 10 exerted potent HIV RT inhibition (IC50 0.06 and 0.05 µM respectively) while compound 6 showed moderate inhibition (IC50 = 3.5 µM). Potent anti-HIV-1 activity in MT-2 cells inoculated by a syncythia-inducing HIV-1 (cat #3 strain) laboratory isolate was exerted by compounds 9 and 10 (EC50 0.62 µM and 0.025 µM, respectively), while compound 6 showed only moderate activity (IC50 = 4.1 µM). In addition, compound 10 showed very good in vitro therapeutic index (TI > 2046), indicating that it is a potential anti-HIV/AIDS drug.

Keywords

EN

HIV reverse transcriptase; HIV-1; inhibitors

• Journal: Acta Biochimica Polonica
• Year: 2007
• Volume: 54
• Issue: 4
• Pages: 863-868

Dates

published

2007

received

2007-08-08

revised

2007-09-03

accepted

2007-09-04

(unknown)

2007-12-08

Contributors

author

Agnieszka Miazga

• Institute of Biochemistry and Biophysics, PAS, Warszawa, Poland

author

Krzysztof Felczak

• Institute of Biochemistry and Biophysics, PAS, Warszawa, Poland

author

Maria A Siwecka

• Institute of Biochemistry and Biophysics, PAS, Warszawa, Poland

author

Andrzej Lipniacki

• Medical Research Center PAS, Warszawa, Poland

author

Andrzej Piasek

• National Medicines Institute, Warszawa, Poland

author

Tadeusz Kulikowski

• Institute of Biochemistry and Biophysics, PAS, Warszawa, Poland

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