Preclinical studies on thiocarboxanilide UC-781 as a virucidal agent

AIDS. 1998 Jul 9;12(10):1129-38. doi: 10.1097/00002030-199810000-00004.


Background: Thiocarboxanilide UC-781 is a highly potent and selective non-nucleoside reverse transcriptase inhibitor (NNRTI) of HIV-1, which also has virucidal properties. Recent studies have shown that UC-781 would seem an ideal candidate for application as a vaginal virucide.

Objective: To investigate the antiviral potency and stability of UC-781 in a lipophilic gel formulation.

Methods: UC-781 was formulated in replens gel at different concentrations and administered intravaginally to rabbits at 5% in replens gel for 10 days. UC-781 was also exposed to temperatures of 4, 37 and 50 degrees C, and to low pH (6.0, 4.3, 2.0 and 1.2). A number of microorganisms were exposed in culture to serial dilutions of UC-781.

Results: The drug was stable under low pH conditions and did not lose its antiviral potency upon 4 h exposure to pH 3.5 (the estimated vaginal pH). UC-781 can be easily formulated into a lipophilic gel (replens; up to 5%) and proved fully stable at 50 degrees C for 30 days. There was no effect on the growth of microorganisms (i.e., Candida and Lactobacillus strains) that are present in the vaginal flora. Neither systemic side-effects, nor local inflammation or damage of the vaginal mucosa or epithelium were observed in rabbits to which 5% UC-781 in replens gel had been administered. UC-781, formulated as 0.5, 0.2 and 0.05% replens gel, and UC-38, alpha-APA and zidovudine, formulated as 0.5 or 0.2% replens gel, were effective in protecting CEM cells in the very beginning against productive HIV-1 replication. This points to an efficient diffusion of the drugs from the lipophilic gel to the hydrophilic culture medium. However, subsequent subcultivations at a dilution rate of 1:10 every 3-4 days resulted in a rapid breakthrough of virus with all drugs except UC-781 in its 0.5 and 0.2% gel formulation. These cultures were fully protected against HIV-1 and remained completely cleared from virus for at least 10 subcultivations.

Conclusions: The virus that emerged under 0.05% UC-781 remained highly sensitive to the NNRTI, including UC-781, in cell culture, suggesting a lack of resistance development under our experimental conditions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acquired Immunodeficiency Syndrome / prevention & control*
  • Administration, Intravaginal
  • Anilides / administration & dosage
  • Anilides / chemistry
  • Anilides / pharmacology*
  • Animals
  • Anti-HIV Agents / administration & dosage
  • Anti-HIV Agents / chemistry
  • Anti-HIV Agents / pharmacology*
  • Bacteria / drug effects
  • Candida / drug effects
  • Cells, Cultured
  • Chromatography, High Pressure Liquid
  • DNA Viruses / drug effects
  • Drug Stability
  • Female
  • Furans / administration & dosage
  • Furans / chemistry
  • Furans / pharmacology*
  • Gels
  • HIV-1 / drug effects*
  • Humans
  • Hydrogen-Ion Concentration
  • Lipids
  • Microbial Sensitivity Tests
  • RNA Viruses / drug effects
  • Rabbits
  • Reverse Transcriptase Inhibitors / pharmacology
  • Temperature
  • Thioamides
  • Vagina / drug effects*
  • Vaginal Creams, Foams, and Jellies


  • Anilides
  • Anti-HIV Agents
  • Furans
  • Gels
  • Lipids
  • Replens
  • Reverse Transcriptase Inhibitors
  • Thioamides
  • Vaginal Creams, Foams, and Jellies
  • UC-781