Simple, short peptide derivatives of a sulfonylindolecarboxamide (L-737,126) active in vitro against HIV-1 wild type and variants carrying non-nucleoside reverse transcriptase inhibitor resistance mutations.
Non-nucleoside reverse transcriptase inhibitors (NNRTIs) active against NNRTI-resistant mutants were obtained by introducing two methyl groups at positions 3 and 5 of the benzenesulfonyl moiety of L-737,126 (1) and coupling one to three glycinamide/alaninamide units to its carboxyamide function. In cell-based assays, the new derivatives showed activities against HIV-1 wild type and NNRTI-resistant mutants [Y181C, K103N-Y181C, and triple mutant (K103R, V179D, P225H) highly resistant to efavirenz] superior to that of the parent indole derivative 1.
Silvestri
Romano
R
Istituto Pasteur-Fondazione Cenci Bolognetti, Dipartimento di Studi Farmaceutici, Università di Roma La Sapienza, Piazzale A. Moro 5, I-00185 Rome, Italy. romano.silvestri@uniroma1.it
Artico
Marino
M
De Martino
Gabriella
G
La Regina
Giuseppe
G
Loddo
Roberta
R
La Colla
Massimiliano
M
Mura
Massimo
M
La Colla
Paolo
P
D019380:Anti-HIV Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D002460:Cell Line; D024882:Drug Resistance, Viral; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D007211:Indoles / Q000138:chemical synthesis / Q000494:pharmacology* / Q000633:toxicity; D009154:Mutation; D018894:Reverse Transcriptase Inhibitors / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D013450:Sulfones / Q000138:chemical synthesis / Q000494:pharmacology* / Q000633:toxicity
C116809:3-benzenesulfonyl-5-chloroindole-2-carboxamide; D019380:Anti-HIV Agents; D007211:Indoles; D018894:Reverse Transcriptase Inhibitors; D013450:Sulfones