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Design, synthesis and structure-activity relationship analysis of bufalin as antitumor agents
Yao-Chen Wu1, Min-Hui Chen1, Meng-Yuan Zhang1
1National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Nanjing University of Chinese Medicine, 138 Xianlin Road, Nanjing, Jiangsu 210023, China.
Bioorganic & Medicinal Chemistry Letters
|July 14, 2026
Summary
Bufalin derivatives were synthesized to test anticancer activity. The C3β-OH group and C17 lactone ring are crucial for bufalin's antitumor effects against lung and cervical cancer cells.
Area of Science:
- Medicinal Chemistry
- Pharmacology
- Oncology
Background:
- Bufalin, a cardiotonic steroid, exhibits anticancer properties.
- Understanding the structure-activity relationships (SAR) of bufalin derivatives is key to developing novel cancer therapeutics.
Purpose of the Study:
- To design and synthesize novel bufalin derivatives.
- To evaluate the antiproliferative activity of these compounds against non-small cell lung cancer (A549) and cervical cancer (HeLa) cell lines.
- To elucidate the essential pharmacophoric elements responsible for bufalin's antitumor activity.
Main Methods:
- Synthesis of two series of bufalin derivatives, including three specific compounds.
- In vitro antiproliferative assays using A549 and HeLa cancer cell lines.
- Structure-activity relationship (SAR) analysis to correlate chemical modifications with biological activity.
Main Results:
- The synthesized bufalin derivatives were evaluated for their antiproliferative effects.
- Methylation of the C3β-hydroxy group significantly reduced antitumor activity.
- Replacing the C17 six-membered unsaturated lactone ring with a five-membered lactone ring also diminished anticancer efficacy.
Conclusions:
- The C3β-hydroxy group is an essential pharmacophore for bufalin's antitumor activity.
- The intact C17 lactone moiety is also critical for the observed anticancer effects.
- These findings provide valuable insights for the rational design of bufalin-based anticancer drugs.
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