Antiviral activity of UIC-PI, a novel inhibitor of the human immunodeficiency virus type 1 protease.
The human immunodeficiency virus type 1 (HIV-1) protease inhibitor UIC-PI (1) was developed via structure-based design and incorporated a novel bis-tetrahydrofuran (bis-THF) ligand in the (R)-(hydroxyethyl)sulfonamide based isostere. The EC(50) and EC(90) of the compound in acutely-infected H9 cells were <1 and approximately 1 nM, respectively. In chronically infected H9/HIV-1(IIIB) cells, the EC(50) and EC(90) were 20 and 50 nM, respectively. In parallel studies comparing UIC-PI and saquinavir in H9/HIV-1(IIIB) cells, viral p24 levels in culture supernatants were an order of magnitude lower with UIC-PI than with saquinavir.
Ghosh
Arun K
AK
Department of Chemistry, University of Illinois at Chicago, 845 West Taylor Street, Chicago, IL 60607, USA.
Pretzer
Elizabeth
E
Cho
Hanna
H
Hussain
Khaja Azhar
KA
Düzgüneş
Nejat
N
D002460:Cell Line; D016655:HIV Core Protein p24 / Q000096:biosynthesis; D016333:HIV Protease; D017320:HIV Protease Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D015497:HIV-1 / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D006801:Humans; D015394:Molecular Structure; D019258:Saquinavir / Q000737:chemistry / Q000494:pharmacology; D013449:Sulfonamides / Q000737:chemistry / Q000494:pharmacology*; D014520:Urethane / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology*
D016655:HIV Core Protein p24; D017320:HIV Protease Inhibitors; D013449:Sulfonamides; C446340:UIC-94003; D014520:Urethane; D016333:HIV Protease; D019258:Saquinavir