Synthesis and cytotoxicity evaluation of 13-n-alkyl berberine and palmatine analogues as anticancer agents.

Abstract

By introducing long carbon-chain alkyl groups at the C-13 position of berberine and palmatine, 13-n-hexyl/13-n-octyl berberine and palmatine chloride analogues 4a-d were synthesized and examined by MTT assays for cytotoxic activity in seven human cancer cell lines (7701QGY, SMMC7721, HepG2, CEM, CEM/VCR, KIII, Lewis), yielding IC₅₀ values of 0.02 ± 0.01-13.58 ± 2.84 μM. 13-n-Octyl palmatine (compound 4d) gave the most potent inhibitor activity, with an IC₅₀ of 0.02 ± 0.01 μM for SMMC7721. In all cases, the 13-n-alkyl berberine and palmatine analogues 4a-d were more cytotoxic than berberine and palmatine. In addition, compounds 4a-d also exhibited more potent cytotoxicity than berberine and palmatine in mice with S180 sarcoma xenografted in vivo. The primary screening results indicated that the 13-n-hexyl/13-n-octyl berberine and palmatine analogues might be valuable source for new potent anticancer drug candidates.

• Authors: Lei Zhang, Jingjing Li, Fei Ma, Shining Yao, Naisan Li, Jing Wang, Yongbin Wang, Xiuzhen Wang, Qizheng Yao
• Journal: Molecules (Basel, Switzerland) (Molecules) Vol. 17 Issue 10 Pg. 11294-302 (Sep 25 2012) ISSN: 1420-3049 [Electronic] Switzerland
• PMID: 23011273 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Berberine Alkaloids
• Berberine
• palmatine

Topics

• Animals
• Antineoplastic Agents (chemical synthesis, pharmacology, toxicity)
• Berberine (chemistry, pharmacology, toxicity)
• Berberine Alkaloids (chemistry, pharmacology, toxicity)
• Cell Line, Tumor
• Hep G2 Cells
• Humans
• Inhibitory Concentration 50
• Male
• Mice
• Xenograft Model Antitumor Assays