Open AccessIn Vitro Anti-Human Immunodeficiency Virus Activities of Z - and E -Methylenecyclopropane Nucleoside Analogues and Their Phosphoro- l -Alaninate Diesters
Author(s) -
Hiroyuki Uchida,
Eiichi Kodama,
Kazuhisa Yoshimura,
Yosuke Maeda,
Pope Kosalaraksa,
Victor Maroun,
Yao-Ling Qiu,
Jiří Žemlička,
Hiroaki Mitsuya
Publication year - 1999
Publication title -
antimicrobial agents and chemotherapy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.07
H-Index - 259
eISSN - 1070-6283
pISSN - 0066-4804
DOI - 10.1128/aac.43.6.1487
Subject(s) - methylenecyclopropane , in vitro , nucleoside , didanosine , moiety , zidovudine , chemistry , biological activity , stereochemistry , biochemistry , human immunodeficiency virus (hiv) , virology , biology , viral disease , catalysis
Nucleoside analogues with a Z- or an E-methylenecyclopropane moiety were synthesized and examined for activity against human immunodeficiency virus type 1 (HIV-1) in vitro. The addition of a methyl phenyl phosphoro-L-alaninate moiety to modestly active analogues resulted in potentiation of their anti-HIV-1 activity. Two such compounds, designated QYL-685 (with 2,6-diaminopurine) and QYL-609 (with adenine), were most potent against HIV-1 in vitro, with 50% inhibitory concentrations of 0.034 and 0.0026 microM, respectively, in MT-2 cell-based assays. Both compounds were active against zidovudine-resistant, didanosine-resistant, and multi-dideoxynucleoside-resistant infectious clones in vitro. Further development of these analogues as potential therapies for HIV-1 infection is warranted.
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