[Mechanism and action characteristics studies of a quinoxalinone compound against HIV-1 replication].
Yao Xue Xue Bao
; 48(6): 860-5, 2013 Jun.
Article
em Zh
| MEDLINE
| ID: mdl-23984519
ABSTRACT
This study is to investigate the mechanism and action characteristics of 6-chloro-3-methyl-4-(2-methyoxycarbonylthiophene-3-sulfonyl)-3, 4-dihydroquinoxa-lin-2-(1 H)-one (XU07011) against HIV-1 replication. XU07011 anti-HIV activity was tested by using VSVG/HIV pseudotype viral system and confirmed by HIV-1 live viruses' infectious assay. Time of addition was used to test HIV-1 reverse transcription process. RNA-dependent DNA polymerase activity and RNase H activity were tested by using enzyme linked immunoabsorbent assay and fluorescence method. Wild type and nine NNRTIs-resistant reverse transcriptase enzymatic models and cell-based pharmacological models were used to evaluate XU07011 bio-characteristics. The results showed that XU07011 inhibited HIV-1 replication with IC50 of (0.057 +/- 0.01) micromol x L(-1) which was comparable to nevirapine [IC50 (0.046 +/- 0.01) micromol x L(-1)]. Mechanism study data indicated that XU07011 blocked HIV-1 reverse transcription process through acting on reverse transcriptase RNA-dependent DNA polymerase with IC 50 of (1.1 +/- 0.3) micromol x L(-1). The compound showed no effect on RNase H activity. XU07011 exhibited better activities comparing with nevirapine on K103N mutated NNRTIs-resistant HIV-1 strains. This study could provide a theoretical basis for novel anti-HIV reagents development.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Quinoxalinas
/
Tiofenos
/
Replicação Viral
/
DNA Polimerase Dirigida por RNA
/
Fármacos Anti-HIV
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
Zh
Ano de publicação:
2013
Tipo de documento:
Article