Effect of human serum on the in vitro anti-HIV-1 activity of 1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)thymine (HEPT) derivatives as related to their lipophilicity and serum protein binding.
Several derivatives of 1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)thymine (HEPT) were examined for their inhibitory effects on the replication of human immunodeficiency virus type 1 (HIV-1) in MT-4 cells in the presence of various concentrations (10-50%) of human serum (HS). Although all HEPT derivatives proved to be highly potent inhibitors of HIV-1 in the presence of 10% fetal bovine serum, some of them were less inhibitory to HIV-1 replication in the presence of HS. The HEPT derivatives were found to be highly bound to HS proteins. Both the anti-HIV-1 activity and HS protein binding of the compounds appeared to be related to their lipophilicity.
Baba
M
M
Department of Microbiology, Fukushima Medical College, Japan.
Yuasa
S
S
Niwa
T
T
Yamamoto
M
M
Yabuuchi
S
S
Takashima
H
H
Ubasawa
M
M
Tanaka
H
H
Miyasaka
T
T
Walker
R T
RT
D000111:Acetylcysteine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D000998:Antiviral Agents / Q000494:pharmacology*; D001769:Blood; D001798:Blood Proteins / Q000378:metabolism*; D002460:Cell Line; D015497:HIV-1 / Q000187:drug effects*; D011485:Protein Binding; D013941:Thymine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D014779:Virus Replication / Q000187:drug effects
D000998:Antiviral Agents; D001798:Blood Proteins; C061818:1-((2-hydroxyethoxy)methyl)-6-(phenylthio)thymine; C070956:3,4-premercapturic acid; C070955:4,3-premercapturic acid; D013941:Thymine; D000111:Acetylcysteine