We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Similar pyridinone compounds with different activities of anti -HIV-1 reverse transcriptase.
- Authors
Yunqi Liu; Xixi Li; Xiaodong Dou; Chao Tian; Zhili Zhang; Junyi Liu; Xiaowei Wang
- Abstract
Among the structurally diverse NNRTIs, pyridinone scaffolds demonstrate high potency against HIV-1 wild type and drug-resistant strains. During the optimization of our pyridinone compound 1 (LAM-trans), we found that the introduction of the N atoms in the C-4 position could dramatically improve the water solubility (7b), whereas protonation of the piperidine N atom resulted in a decrease in its hydrophobic interaction with the binding pocket. In particular, protonation altered the orientation of the alicyclic rings in the hydrophobic pocket, thus impeding the formation of key halogen bond and eventually leading to a huge change in anti-HIV-1 RT activity. These results provided theoretical and experimental basis for the subsequent structural modification of pyridinone compounds.
- Subjects
PYRIDONE derivatives; REVERSE transcriptase; MOLECULAR docking; HYDROPHOBIC interactions; ANTI-HIV agents
- Publication
Journal of Chinese Pharmaceutical Sciences, 2018, Vol 27, Issue 7, p469
- ISSN
1003-1057
- Publication type
Article
- DOI
10.5246/jcps.2018.07.048