2. Academic Validation
  3. Anti-HIV diarylpyrimidine-quinolone hybrids and their mode of action

Anti-HIV diarylpyrimidine-quinolone hybrids and their mode of action

  • Bioorg Med Chem. 2015 Jul 1;23(13):3860-8. doi: 10.1016/j.bmc.2015.03.037.
Tian-Qi Mao 1,  Qiu-Qin He 2,  Zheng-Yong Wan 3,  Wen-Xue Chen 3,  Fen-Er Chen 4,  Gang-Feng Tang 3,  Erik De Clercq 5,  Dirk Daelemans 5,  Christophe Pannecouque 5
Affiliations

Affiliations

  • 1 Department of Chemistry, Fudan University, Shanghai 200433, People's Republic of China; Institute of Biomedical Science, Fudan University, Shanghai 200433, People's Republic of China.
  • 2 Department of Chemistry, Fudan University, Shanghai 200433, People's Republic of China. Electronic address: qqhe@fudan.edu.cn.
  • 3 Department of Chemistry, Fudan University, Shanghai 200433, People's Republic of China.
  • 4 Department of Chemistry, Fudan University, Shanghai 200433, People's Republic of China; Institute of Biomedical Science, Fudan University, Shanghai 200433, People's Republic of China. Electronic address: rfchen@fudan.edu.cn.
  • 5 Rega Institute for Medical Research, Katholieke Universiteit Leuven, 10 Minderbroedersstraat, B-3000 Leuven, Belgium.
PMID: 25907370 DOI: 10.1016/j.bmc.2015.03.037
Abstract

A molecular hybridization approach is a powerful tool in the design of new molecules with improved affinity and efficacy. In this context, a series of diarylpyrimidine-quinolone hybrids were synthesized and evaluated against both wt HIV-1 and mutant viral strains. The most active hybrid 5a displayed an EC50 value of 0.28±0.07μM against HIV-1 IIIB. A couple of enzyme-based assays clearly pinpoint a RT-targeted mechanism of action. Docking studies revealed that these hybrids could be well located in the NNIBP of HIV-1 RT despite the bulky and polar properties of a Quinolone 3-carboxylic acid moiety in the molecules.

Keywords

Anti-HIV; Diarylpyrimidine–quinolone hybrids; HIV-1 reverse transcriptase; Integrase.

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