2. Academic Validation
  3. Design and synthesis of hybrids of diarylpyrimidines and diketo acids as HIV-1 inhibitors

Design and synthesis of hybrids of diarylpyrimidines and diketo acids as HIV-1 inhibitors

  • Bioorg Med Chem Lett. 2017 Apr 15;27(8):1640-1643. doi: 10.1016/j.bmcl.2017.03.009.
Ping Xue 1,  Huan-Huan Lu 1,  Yuan-Yuan Zhu 2,  Xiu-Lian Ju 1,  Christophe Pannecouque 3,  Xiao-Jiao Zheng 1,  Gen-Yan Liu 1,  Xiu-Lan Zhang 1,  Shuang-Xi Gu 4
Affiliations

Affiliations

  • 1 Key Laboratory for Green Chemical Process of Ministry of Education, School of Chemical Engineering & Pharmacy, Wuhan Institute of Technology, Wuhan 430205, China.
  • 2 School of Chemistry and Environmental Engineering, Wuhan Institute of Technology, Wuhan 430205, China. Electronic address: yyzhu531@163.com.
  • 3 KU Leuven, Department of Microbiology and Immunology, Laboratory of Virology and Chemotherapy, Rega Institute for Medical Research, B-3000 Leuven, Belgium.
  • 4 Key Laboratory for Green Chemical Process of Ministry of Education, School of Chemical Engineering & Pharmacy, Wuhan Institute of Technology, Wuhan 430205, China. Electronic address: shuangxigu@163.com.
PMID: 28314598 DOI: 10.1016/j.bmcl.2017.03.009
Abstract

Based on the strategy of molecular hybridization, diketo acid fragment as a classical phamacophore of integrase inhibitors was introduced to Reverse Transcriptase inhibitors diarylpyrimidines to design a series of diarylpyrimidine-diketo acid hybrids (DAPY-DKAs). The target molecules 10b and 11b showed inhibitory activities against WT HIV-1 with EC50 values of 0.18μM and 0.14μM, respectively. And the results of molecular docking demonstrated the potential binding mode and revealed that the DKA moiety and its ester could both be tolerated in the nonnucleoside binding site (NNBS) of HIV-1 RT.

Keywords

AIDS; Diarylpyrimidines; Diketo acids; HIV-1 inhibitors; Integrase; Molecular hybridization; Reverse transcriptase.

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