Novel Betulinic Acid-Nucleoside Hybrids with Potent Anti-HIV Activity

  • ACS Med Chem Lett. 2020 Sep 9;11(11):2290-2293. doi: 10.1021/acsmedchemlett.0c00414.
Qiang Wang  1  2  3 ,  Yujiang Li  1 ,  Liyun Zheng  3 ,  Xiaowan Huang  3 ,  Yanli Wang  2 ,  Chin-Ho Chen  4 ,  Yung-Yi Cheng  5 ,  Susan L Morris-Natschke  5 ,  Kuo-Hsiung Lee  5  6
Affiliations
  • 1. High & New Technology Research Center of Henan Academy of Sciences, Zhengzhou 450002, China.
  • 2. National Health Commission Key Laboratory of Birth Defect Prevention, Zhengzhou 450002, China.
  • 3. Institute of Medical and Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450052, China.
  • 4. Surgical Science, Department of Surgery, Duke University Medical Center, Durham, North Carolina 27710, United States.
  • 5. Natural Products Research Laboratories, UNC Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, North Carolina 27599-7568, United States.
  • 6. Chinese Medicine Research and Development Center, China Medical University and Hospital, Taichung 40402, Taiwan.
PMID: 33214842 DOI: 10.1021/acsmedchemlett.0c00414
Abstract

Novel betulinic/betulonic acid-nucleoside hybrids were synthesized as possible new anti-HIV agents. Among the synthesized hybrids, two compounds were highly effective against HIV. Compared with AZT and DSB, compounds 10a (IC50 = 0.0078 μM, CC50 = 9.6 μM) and 10b (IC50 = 0.020 μM, CC50 = 23.8 μM) showed more potent or equipotent, respectively, anti-HIV activity but displayed lower cytotoxicity.