N-(adamantyl-1)methyl, N-(adamantyl-2), and N-(omega-aminodecyl) amides of vancomycin, eremomycin, and dechloroeremomycin aglycons and their des-(N-Me-D-Leu) derivatives were synthesized and their antibacterial and anti-HIV activities were investigated. Carboxamides with an intact peptide core demonstrated activity against glycopeptide-susceptible and -resistant bacteria (1-32 microM). N-(adamantyl-1)methylcarboxamide of eremomycin aglycons had good antiretroviral activity (1.6 microM against HIV-1). Compounds with destroyed peptide core [des-(N-Me-D-Leu)-aglycon amides] were inactive against both glycopeptide-sensitive and -resistant bacteria. (Adamantyl-1)methylamide of des-(N-Me-D-Leu)-eremomycin aglycon had good antiretroviral activity (EC50 of 5.5 microM for HIV-1 and 3.5 microM for HIV-2). (Adamantyl-1)methylamides of eremomycin aglycon and its des-(N-Me-d-Leu)-derivative are the most promising and selective antiretroviral agents. Their ability to induce bacterial resistance to glycopeptide antibiotics during prolonged administration may be expected to be very low or absent. This might make the use of these derivatives feasible in the prolonged therapy or prophylaxis of HIV infections.

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.