2. Academic Validation
  3. New phorbol ester derivatives as potent anti-HIV agents

New phorbol ester derivatives as potent anti-HIV agents

  • Bioorg Med Chem Lett. 2021 Oct 15:50:128319. doi: 10.1016/j.bmcl.2021.128319.
Qi-Run Li 1,  Yung-Yi Cheng 2,  Lei Zhao 1,  Xiao-Lei Huang 1,  Xiao-Gang Jiang 1,  Ya-Dong Cui 1,  Susan L Morris-Natschke 2,  Masuo Goto 2,  Chin-Ho Chen 3,  Kuo-Hsiung Lee 4,  Dao-Feng Chen 5,  Jian Zhang 6
Affiliations

Affiliations

  • 1 College of Pharmaceutical Science, Soochow University, Suzhou 215123, PR China.
  • 2 Natural Products Research Laboratories, UNC Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC 27599, United States.
  • 3 Surgical Oncology Research Facility, Duke University Medical Center, Box 2926, Durham, NC 27710, United States.
  • 4 Natural Products Research Laboratories, UNC Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC 27599, United States; Chinese Medicine Research and Development Center, China Medical University and Hospital, Taichung 40402, Taiwan. Electronic address: khlee@unc.edu.
  • 5 Department of Pharmacognosy, School of Pharmacy, Fudan University, Shanghai 201203, PR China. Electronic address: dfchen@shmu.edu.cn.
  • 6 College of Pharmaceutical Science, Soochow University, Suzhou 215123, PR China. Electronic address: jianzhang@suda.edu.cn.
PMID: 34403728 DOI: 10.1016/j.bmcl.2021.128319
Abstract

Tigliane esters show many biological activities, including anti-HIV-1 activity. Our aim in this study was to establish structure-anti-HIV activity relationships for four series of tigliane-type Diterpenoids. We synthesized and evaluated 29 new phorbol ester derivatives for anti-HIV activity and for cytotoxicity against human tumor cell lines. Among them, three derivatives, two phorbol-13-monoesters (5d and 5e) and a phorbol-12,13-diester (6a), showed significant anti-HIV activity. We found that better anti-HIV activity was often associated with a shorter acyl ester at C-13. Particularly, compounds with a phenyl ring in the ester side chain exhibited excellent anti-HIV activity and had good safety indexes. Due to its significant anti-HIV potency with a high selectivity index, phorbol-12,13-dicinnamoate (6a) was chosen as the potential candidate for further preclinical trials.

Keywords

Anti-HIV activity; Cytotoxicity; Non-tumor-promoting; Phorbol esters; Tigliane diterpenoids.

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