Synthesis and anti-HIV properties of novel 6-phenylselenenyl-5-propyluracils.
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 (IC(50) 0.06 and 0.05 microM respectively) while compound 6 showed moderate inhibition (IC(50) = 3.5 microM). 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 (EC(50) 0.62 microM and 0.025 microM, respectively), while compound 6 showed only moderate activity (IC(50) = 4.1 microM). In addition, compound 10 showed very good in vitro therapeutic index (TI > 2046), indicating that it is a potential anti-HIV/AIDS drug.
Miazga
Agnieszka
A
Institute of Biochemistry and Biophysics, PAS, Warszawa, Poland.
Felczak
Krzysztof
K
Siwecka
Maria A
MA
Lipniacki
Andrzej
A
Piasek
Andrzej
A
Kulikowski
Tadeusz
T
D019380:Anti-HIV Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D002460:Cell Line; D004797:Enzyme-Linked Immunosorbent Assay; D015497:HIV-1 / Q000187:drug effects; D006801:Humans; D018894:Reverse Transcriptase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014498:Uracil / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology
D019380:Anti-HIV Agents; D018894:Reverse Transcriptase Inhibitors; C002652:5-propyluracil; D014498:Uracil