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2007 | 54 | 4 | 863-868
Article title

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

Content
Title variants
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.
Year
Volume
54
Issue
4
Pages
863-868
Physical description
Dates
published
2007
received
2007-08-08
revised
2007-09-03
accepted
2007-09-04
(unknown)
2007-12-08
References
  • Cosword NDP, Schinazi RF (1991) J Org Chem 56: 2161-2165.
  • De Clercq E (1995) J Med Chem 38: 2491-2517.
  • Eberle J, Knopf ChW (1996) Methods Enzymol 275: 257-276.
  • Goudgaon NM, Schinazi RF (1991) J Med Chem 34: 3305-3309.
  • Goudgaon NM, McMillan A, Schinazi RF (1992) Antivir Chem Chemother 3: 263-266.
  • Kim D-K, Kim Y-W, Gam J, Kim G, Lim J, Lee N, Kim H-T, Kim KH (1996) J Heterocycl Chem 33: 1275-1283.
  • Mossman T (1983) J Immunol Methods 65: 55-63.
  • Ni L, Schinazi RF, Boudinot FD (1995) Antiviral Res 27: 39-47.
  • Pan B-C, Chen Z-H, Piras G, Dutschman GE, Rowe EC, Chent Y-C, Chu S-H (1994) J Heterocycl Chem 31: 177-185.
  • Rosowsky A, Kim S-H, Wick M (1981) J Med Chem 24: 1177-1181.
  • Tanaka H, Baba M, Hayakawa H, Sakamaki T, Miyasaka T, Ubasawa M, Takashima H, Sekiya K, Nitta I, Shigeta S, Walker RT, Balzarini J, De Clercq E (1991) J Med Chem 34: 349-357.
  • Ubasawa M, Takashima H, Sekiya K (1995) Chem Pharm Bull 43: 142-143.
  • Vandamme A-M, Van Vaerenbergh K, De Clercq E (1998) Antivir Chem Chemother 9: 187-203.
Document Type
Publication order reference
YADDA identifier
bwmeta1.element.bwnjournal-article-abpv54p863kz
Identifiers
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