SRR-SB3, a disulfide-containing macrolide that inhibits a late stage of the replicative cycle of human immunodeficiency virus

Antimicrob Agents Chemother. 1997 Feb;41(2):262-8. doi: 10.1128/AAC.41.2.262.


From a series of macrocyclic diamides possessing the disulfide linkage, only SRR-SB3, a compound that complexes with zinc, was found to inhibit human immunodeficiency virus type 1 (HIV-1; strain IIIB) replication at a concentration of 1.8 to 6.5 micrograms/ml in MT-4, CEM, and peripheral blood mononuclear cells. SRR-SB3 was toxic to MT-4 cells at a concentration of 15.9 micrograms/ml, resulting in a selectivity index of 9 in these cells. This macrolide was also effective against various other HIV-1 strains, including clinical isolates and HIV-1 strains resistant to protease inhibitors and nucleoside and nonnucleoside reverse transcriptase inhibitors. It was also active against various HIV-2 strains, simian immunodeficiency virus (strain MAC251), and Moloney murine sarcoma virus, but not against viruses other than retroviruses. In addition, the compound was found to inhibit chronic HIV-1 infections in vitro. The compound in combination with other antiviral agents, such as zidovudine, zalcitabine, and stavudine, showed an effect that was between additive and synergistic. Time-of-addition experiments indicated that SRR-SB3 acts at a late stage of the HIV-1 replicative cycle.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-HIV Agents / pharmacology*
  • Benzamides / pharmacology*
  • Cell Line
  • DNA, Viral / analysis
  • Disulfides / pharmacology*
  • Drug Synergism
  • HIV-1 / drug effects*
  • HIV-1 / physiology
  • Humans
  • Mice
  • Moloney murine sarcoma virus / drug effects
  • Polymerase Chain Reaction
  • Retroviridae Infections / drug therapy
  • Retroviridae Infections / virology
  • Reverse Transcriptase Inhibitors / pharmacology
  • Sarcoma, Experimental / drug therapy
  • Sarcoma, Experimental / virology
  • Tumor Virus Infections / drug therapy
  • Tumor Virus Infections / virology
  • Virus Replication / drug effects*


  • Anti-HIV Agents
  • Benzamides
  • DNA, Viral
  • Disulfides
  • Reverse Transcriptase Inhibitors
  • SRR SB3