Antiretroviral activity of semisynthetic derivatives of glycopeptide antibiotics.
A variety of semisynthetic derivatives of natural antibacterial glycopeptide antibiotics such as vancomycin, eremomycin, ristocetin A, teicoplanin A(2)-2, DA-40926, their aglycons, and also the products of their partial degradation with a destroyed or modified peptide core show marked anti-retroviral activity in cell culture. In particular, aglycon antibiotic derivatives containing various substituents of a preferably hydrophobic nature displayed activity against human immunodeficiency virus type 1 (HIV-1), HIV-2, and Moloney murine sarcoma virus at a 50% inhibitory concentration in the lower micromolar (1-5 microM) concentration range while not being cytostatic against human lymphocytic cells at 250 microM or higher. The mode of anti-HIV action of the antibiotic aglycon derivatives could be ascribed to inhibition of the viral entry process.
Balzarini
Jan
J
Rega Institute for Medical Research, Katholieke Universiteit Leuven, B-3000 Leuven, Belgium.
Pannecouque
Christophe
C
De Clercq
Erik
E
Pavlov
Andrey Y
AY
Printsevskaya
Svetlana S
SS
Miroshnikova
Olga V
OV
Reznikova
Marina I
MI
Preobrazhenskaya
Maria N
MN
D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry*; D019380:Anti-HIV Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002460:Cell Line; D003588:Cytopathogenic Effect, Viral / Q000187:drug effects; D005347:Fibroblasts / Q000187:drug effects / Q000821:virology; D006020:Glycopeptides; D015497:HIV-1 / Q000187:drug effects*; D015498:HIV-2 / Q000187:drug effects*; D006801:Humans; D051379:Mice; D008980:Moloney murine sarcoma virus / Q000187:drug effects*; D013329:Structure-Activity Relationship
D000900:Anti-Bacterial Agents; D019380:Anti-HIV Agents; D000998:Antiviral Agents; D006020:Glycopeptides