title: 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.affiliation: School of Pharmacy, China Pharmaceutical University, Nanjing 210009, Jiangsu, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
authors.forename: Jingjing
authors.initials: J
authors.lastname: Li
authors.forename: Fei
authors.initials: F
authors.lastname: Ma
authors.forename: Shining
authors.initials: S
authors.lastname: Yao
authors.forename: Naisan
authors.initials: N
authors.lastname: Li
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.forename: Yongbin
authors.initials: Y
authors.lastname: Wang
authors.forename: Xiuzhen
authors.initials: X
authors.lastname: Wang
authors.forename: Qizheng
authors.initials: Q
authors.lastname: Yao
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity*; D001599:Berberine / Q000737:chemistry* / Q000494:pharmacology / Q000633:toxicity*; D001600:Berberine Alkaloids / Q000737:chemistry* / Q000494:pharmacology / Q000633:toxicity*; D045744:Cell Line, Tumor; D056945:Hep G2 Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D008297:Male; D051379:Mice; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D001600:Berberine Alkaloids; D001599:Berberine; C005413:palmatine