Mechanism and action characteristics studies of a quinoxalinone compound against HIV-1 replication

• Published in: Yao hsüeh hsüeh pao Vol. 48; no. 6; p. 860
• Main Authors: Ba, Ming-Yu, Cao, Ying-Li, Xu, Bai-Ling, Guo, Ying
• Format: Journal Article
• Language: Chinese
• Published: China 01.06.2013
• Subjects: Anti-HIV Agents - chemistry; Anti-HIV Agents - pharmacology; Drug Resistance, Viral; HEK293 Cells; HIV-1 - physiology; Humans; Inhibitory Concentration 50; Molecular Structure; Nevirapine - pharmacology; Quinoxalines - pharmacology; Ribonuclease H - metabolism; RNA-Directed DNA Polymerase - metabolism; Thiophenes - pharmacology; Virus Replication - drug effects
• ISSN: 0513-4870

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 transcri