Synthesis, antiviral and contraceptive activities of nucleoside-sodium cellulose sulfate acetate and succinate conjugates

Hitesh K. Agarwal, Anil Kumar, Gustavo F. Doncel, Keykavous Parang

Research output: Contribution to journalArticle

Abstract

Chemical conjugates between sodium cellulose sulfate (CS), displaying contraceptive and HIV-entry inhibiting properties, and nucleoside reverse transcriptase inhibitors (NRTIs) (3′-azido-2′,3′- dideoxythymidine (AZT), 3′-fluoro-2′,3′-dideoxythymidine (FLT), or 2′,3′-dideoxy-3′-thiacytidine (3TC)) were designed to simultaneously provide contraceptive and anti-HIV activity. Two linkers, acetate and succinate, were used to conjugate the nucleoside analogs with CS. The conjugates containing cellulose sulfate-acetate (CSA) (e.g., AZT-CSA and FLT-CSA) were found to be more potent than CS and other conjugates (e.g., AZT-succinate-CS, and FLT-succinate-CS). The presence of both sulfate and the acetate groups on cellulose were critical for generating maximum anti-HIV activity. In addition to showing equal potency against wild-type and multidrug resistant HIV-1, the AZT-CSA conjugate displayed significant contraceptive activity in an animal model, providing the initial proof-of-concept for the design and synthesis of dual-activity compounds based on these combinations.

Original languageEnglish (US)
Pages (from-to)6993-6997
Number of pages5
JournalBioorganic and Medicinal Chemistry Letters
Volume20
Issue number23
DOIs
StatePublished - Dec 1 2010
Externally publishedYes

Keywords

  • 3TC
  • Anti-HIV
  • AZT
  • Cellulose acetate
  • Contraceptive
  • FLT
  • Nucleoside
  • Sodium cellulose sulfate

ASJC Scopus subject areas

  • Pharmaceutical Science
  • Drug Discovery
  • Organic Chemistry
  • Molecular Medicine
  • Molecular Biology
  • Clinical Biochemistry
  • Biochemistry

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