Structure based design and evaluation of benzoheterocycle derivatives as potential dual HIV-1 protease and reverse transcriptase inhibitors

  • Eur J Med Chem. 2023 Jan 15;246:114981. doi: 10.1016/j.ejmech.2022.114981.
Mei Zhu  1 ,  Qi Shan  2 ,  Ling Ma  1 ,  Biao Dong  1 ,  Juxian Wang  1 ,  Guoning Zhang  1 ,  Minghua Wang  1 ,  Jinming Zhou  3 ,  Shan Cen  4 ,  Yucheng Wang  5
Affiliations
  • 1. Institute of Medicinal Biotechnology, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, 100050, China.
  • 2. Tianjin Institute of Pharmaceutical Research, Tianjin, 300462, China.
  • 3. Key Laboratory of the Ministry of Education for Advanced Catalysis Materials, Department of Chemistry, Zhejiang Normal University, Jinhua, 321004, China. Electronic address: [email protected].
  • 4. Institute of Medicinal Biotechnology, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, 100050, China. Electronic address: [email protected].
  • 5. Institute of Medicinal Biotechnology, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, 100050, China. Electronic address: [email protected].
PMID: 36481598 DOI: 10.1016/j.ejmech.2022.114981
Abstract

The development of dual inhibitors of HIV-1 protease and Reverse Transcriptase is an attractive strategy for multi-target therapeutic of AIDS, which may be privileged in delaying the occurrence of drug resistance. We herein designed a novel kind of dual inhibitors with benzofuran or indole cores. Biological results showed that a number of inhibitors displayed significant activity against both HIV-1 protease and Reverse Transcriptase. Among which, inhibitor 10f exhibited a good correlation with an approximate ratio of 1: 2 between the two Enzymes. Furthermore, the dual inhibitors illustrated similar potency against both the wild-type virus and drug-resistant mutant. In addition, the molecular dynamic simulation studies verified the dual actions of such inhibitors.

Keywords
Benzofuran; HIV-1 dual inhibitor; Indole; Molecular dynamic simulation studies; Multidrug resistance; Protease; Reverse transcriptase.
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