2. Academic Validation
  3. Design, synthesis and cytotoxic activity of novel sulfonylurea derivatives of podophyllotoxin

Design, synthesis and cytotoxic activity of novel sulfonylurea derivatives of podophyllotoxin

  • Bioorg Med Chem. 2014 Jan 1;22(1):204-10. doi: 10.1016/j.bmc.2013.11.035.
Zhi-Jun Zhang 1,  Jing Tian 1,  Li-Ting Wang 2,  Mei-Juan Wang 1,  Xiang Nan 1,  Liu Yang 3,  Ying-Qian Liu 4,  Susan L Morris-Natschke 2,  Kuo-Hsiung Lee 5
Affiliations

Affiliations

  • 1 School of Pharmacy, Lanzhou University, Lanzhou 730000, PR China.
  • 2 Natural Products Research Laboratories, UNC Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC 27599, United States.
  • 3 Environmental and Municipal Engineering School, Lanzhou Jiaotong University, Lanzhou 730000, PR China.
  • 4 School of Pharmacy, Lanzhou University, Lanzhou 730000, PR China. Electronic address: yqliu@lzu.edu.cn.
  • 5 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, Taiwan. Electronic address: khlee@email.unc.edu.
PMID: 24332656 DOI: 10.1016/j.bmc.2013.11.035
Abstract

Three series of novel sulfonylurea podophyllotoxin derivatives were designed, synthesized, and evaluated for in vitro cytotoxicity against four tumor cell lines (A-549, DU-145, KB and KBvin). Compounds 14c (IC₅₀: 1.41-1.76 μM) and 14e (IC₅₀: 1.72-2.01 μM) showed superior cytotoxic activity compared with etoposide (IC₅₀: 2.03 to >20 μM), a clinically available Anticancer drug. Significantly, most of the compounds exhibited comparable cytotoxicity against the drug-resistant tumor cell line KBvin, while etoposide lost activity completely. Preliminary structure-activity relationship (SAR) correlations indicated that the 4'-O-methyl functionality in podophyllotoxin analogues may be essential to maintain cytotoxic activity, while an arylsulfonylurea side chain at podophyllotoxin's 4β position can significantly improve cytotoxic activity.

Keywords

Cytotoxic activity; Podophyllotoxin; Sulfonylurea; Synthesis.

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