期刊
ORGANIC & BIOMOLECULAR CHEMISTRY
卷 12, 期 41, 页码 8308-8317出版社
ROYAL SOC CHEMISTRY
DOI: 10.1039/c4ob01333f
关键词
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资金
- NSFC [81172935, 81373255]
- Key Project of Ministry of Education [313040]
- Hubei Province's Outstanding Medical Academic Leader Program
- Scientific and Technological Innovative Research Team of Wuhan [2013070204020048]
- National Mega Project on Major Drug Development [2011ZX09401-302]
- Fundamental Research Funds for the Central Universities [2014306020201, 2042014kf0204]
A series of non-nucleoside reverse transcriptase inhibitors derived from indole-based a-amino acids were designed and synthesized. Their inhibitory activities were detected by a TZM-bl cell assay on HIV virus type HIV-1(IIIB). The comprehensive understanding of the SAR was obtained by utilizing the variation of the substituents of the indole-based alpha-amino acids. From the screened compounds, the novel inhibitors 19 and 29 were identified to be highly potent candidates with EC50 values of 0.060 mu M and 0.045 mu M respectively (CC50 values of 109.545 mu M and 49.295 mu M and SI values of 1825.8 and 1095.4). In most cases, the variation of substituents at different positions had a significant effect on the potency of activities. The results also indicate that the indole-based alpha-amino acids as efficient NNRTIs displayed comparable anti-HIV-1 activities to the reference drug NVP. We hope the identification of these indole-based amino acids as efficient NNRTIs of RT could stimulate researchers to develop more diversified anti-HIV drugs.
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