Journal of Chinese Pharmaceutical Sciences ›› 2017, Vol. 26 ›› Issue (7): 512-520.DOI: 10.5246/jcps.2017.07.057

• Original articles • Previous Articles     Next Articles

Docking and field-based QSAR studies of S-DABOs as HIV-1 reverse transcriptase inhibitors

Ningning Fan1, Zhenming Liu2*, Xiaowei Wang1*, Junyi Liu1,2*   

  1. 1. Department of Chemical Biology, School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing 100191, China
    2. State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing 100191, China
  • Received:2017-05-12 Revised:2017-05-31 Online:2017-07-28 Published:2017-06-20
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  • Supported by:

    National Natural Science Foundation of China (Grant No. 21172014, 20972011, 21042009, 21272017 and 81172917) and Grants from the Ministry of Science and Technology of China (Grant No. 2009ZX09301-010).


HIV-1 reverse transcriptase (RT) inhibitors are major components of HAART (highly active antiviral therapy). The S-DABOs (dihydro-alkylthio-benzyl-oxopyrimidines) series and their similar skeletons have exhibited preferable activities to inhibit HIV-1 RT. In the present study, we generated field-based QSAR models using common structure alignment, which was characterized by Gaussian steric, electrostatic, hydrophobic, hydrogen bond donor, hydrogen bond acceptor and aromatic ring fields (R2 = 0.8421, R2CV = 0.5949 for the training set, Q2 = 0.5486, Pearson-r = 0.7460 for the test set). Docking, pocket surface and contourmap analyses were carried out. Key pharmacophore features were investigated, including (i) π-π interaction with residue Tyr181, Tyr188 and Trp229, σ-π interaction with His236, (ii) hydrogen bond with residue Lys101 and halogen bond with residue Tyr188. The docking analysis and field-based QSAR models could provide reasonable guidance in the rational design of potent HIV-1 RT inhibitors.

Key words: HIV-1 reverse transcriptase, S-DABOs, Molecular docking, Field-based QSAR

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