2. Academic Validation
  3. Incorporation of Privileged Structures into Bevirimat Can Improve Activity against Wild-Type and Bevirimat-Resistant HIV-1

Incorporation of Privileged Structures into Bevirimat Can Improve Activity against Wild-Type and Bevirimat-Resistant HIV-1

  • J Med Chem. 2016 Oct 13;59(19):9262-9268. doi: 10.1021/acs.jmedchem.6b00461.
Yu Zhao 1,  Qiong Gu 1 2,  Susan L Morris-Natschke 1,  Chin-Ho Chen 3,  Kuo-Hsiung Lee 1 4
Affiliations

Affiliations

  • 1 Natural Products Research Laboratories, UNC Eshelman School of Pharmacy, University of North Carolina , Chapel Hill, North Carolina 27599-7568, United States.
  • 2 Research Center for Drug Discovery, School of Pharmaceutical Sciences, Sun Yat-sen University , Guangzhou 510006, People's Republic of China.
  • 3 Surgical Oncology Research Facility, Duke University Medical Center , Box 2926, Durham, North Carolina 27710, United States.
  • 4 Chinese Medicine Research and Development Center, China Medical University and Hospital , 404 Taichung, Taiwan.
PMID: 27676157 DOI: 10.1021/acs.jmedchem.6b00461
Abstract

Two "privileged fragments", caffeic acid and piperazine, were integrated into bevirimat producing new derivatives with improved activity against HIV-1/NL4-3 and NL4-3/V370A carrying the most prevalent bevirimat-resistant polymorphism. The activity of one of these, 18c, was increased by 3-fold against NL4-3 and 51-fold against NL4-3/V370A. Moreover, 18c is a maturation inhibitor with improved metabolic stability. Our study suggested that integration of privileged motifs into promising natural product skeletons is an effective strategy for discovering potent derivatives.

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