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

• Published in: Acta biochimica polonica Vol. 54; no. 4; pp. 863 - 868
• Main Authors: Miazga, A, Felczak, K, Siwecka, MA, Lipniacki, A, Piasek, A, Kulikowski, T
• Format: Journal Article
• Language: English
• Published: 01.01.2007
• Subjects: Human immunodeficiency virus; Human immunodeficiency virus 1
• ISSN: 0001-527X

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, 1-ethoxymethyl-6-phenylselenenyl-5-propyluracil and l-benzyloxymethyl-6-phenylselenenyl-5-propyluracil. 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 (IC sub(50) 0.06 and 0.05 mu M respectively) while compound 6 showed moderate inhibition (IC sub(50) = 3.5 mu M). Potent anti-HTV-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 (EC sub(50) 0.62 mu M and 0.025 mu M, respectively), while compound 6 showed only moderate activity (IC sub(50) = 4.1 mu M). In addition, compound 10 showed very good in vitro therapeutic index (TI > 2046), indicating that it is a potential anti-HIV/AIDS drug.