title: Semi-synthesis and antitumor activity of 6-isomers of 5, 8-O-dimethyl acylshikonin derivatives.
abstract: We recently discovered that 5, 8-O-dimethyl acylshikonin derivatives displayed the selectivity towards MCF-7 and no toxicity to normal cells. Herein, a series of the corresponding 6-isomers of 5, 8-O-dimethyl acylshikonin derivatives were synthesized starting from shikonin. In vitro evidence of the cytotoxicities indicated that most of thecompounds were more active than or comparative to shikonin and retained the selectivity against MCF-7, MDA-MB-231 besides no toxicity in the normal cells. Also, in vivo anticancer activity of the positional isomers 5p, 6c further showed that 6-isomers of 5, 8-O-dimethyl acylshikonin derivatives were more active than their corresponding 2-isomers. Thus, we may conclude that the position of the side chain of shikonin attached to 5,8-dimethoxy -1,4-naphthoquinone is associated with the antitumor activity.
authors.affiliation: School of Pharmacy, Shanghai Jiaotong University, 800 Dongchuan Road, Shanghai 200240, China.
authors.forename: Wen
authors.initials: W
authors.lastname: Zhou
authors.forename: Xu
authors.initials: X
authors.lastname: Zhang
authors.forename: Ling
authors.initials: L
authors.lastname: Xiao
authors.forename: Jing
authors.initials: J
authors.lastname: Ding
authors.forename: Quan-Hua
authors.initials: QH
authors.lastname: Liu
authors.forename: Shao-Shun
authors.initials: SS
authors.lastname: Li
mesh_terms: D000215:Acylation; D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D002470:Cell Survival; D004354:Drug Screening Assays, Antitumor; D005260:Female; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects*; D006801:Humans; D020128:Inhibitory Concentration 50; D007536:Isomerism; D008297:Male; D051379:Mice; D009285:Naphthoquinones / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology; D009369:Neoplasms / Q000188:drug therapy / Q000473:pathology; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D009285:Naphthoquinones; C016101:shikonin; C035342:1,4-naphthoquinone