Synthesis and Cytotoxicity Evaluation of 13-n-Alkyl Berberine and Palmatine Analogues as Anticancer Agents

Molecules

Lei Zhang¹  Jingjing Li¹  Fei Ma¹  Shining Yao¹  Naisan Li¹  Jing Wang¹  Yongbin Wang¹  Xiuzhen Wang¹ 

[1] ¹School of Pharmacy, China Pharmaceutical University, Nanjing 210009, Jiangsu, China

关键词: berberine;    palmatine;    alkylation;    cytotoxicity;    antitumor;   

DOI  :  10.3390/molecules171011294

来源: mdpi

【 摘 要 】

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.

【 授权许可】

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