HIV-1 protease inhibitors containing an N-hydroxyamino acid core structure.
Two series of peptidomimetics containing an N-hydroxyamino acid core structure were prepared by mixed solution solid-phase synthesis and tested for inhibitory activity against the human immunodeficiency virus (HIV-1) protease (Pr) and the virus in cell culture. In general, N-hydroxy Gly containing pseudopeptides displayed modest HIV Pr inhibition (IC50 > or = 930 nM). In the N-hydroxy Phe derivatives, Fmoc-Phe-psi[CO-N(OH)]-Phe-Pro-NHtBu was the best inhibitor of the series (IC50 = 144nM) showing satisfactory inhibition of HIV replication in cell culture (ED50 = 98 nM) and remarkable stability against cell culture and plasma enzymes.
Marastoni
M
M
Dipartimento di Scienze Farmaceutiche, Università di Ferrara, Italy. mrn@dns.unife.it
Bazzaro
M
M
Salvadori
S
S
Bortolotti
F
F
Tomatis
R
R
D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid; D017320:HIV Protease Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D015497:HIV-1 / Q000187:drug effects* / Q000201:enzymology*; D006801:Humans; D006877:Hydroxamic Acids / Q000138:chemical synthesis / Q000494:pharmacology; D007700:Kinetics
D017320:HIV Protease Inhibitors; D006877:Hydroxamic Acids