Semi-synthesis and anti-tumor activity of 5,8-O-dimethyl acylshikonin derivatives.
A set of twenty-two 5,8-O-dimethyl acylshikonin derivatives were designed and synthesized starting from shikonin. The cell-based investigation demonstrated that these dimethylated derivatives were less active than or equally effective to shikonin. However, the selective cytotoxicities toward MCF-7 were found among these derivatives, together with no toxicity in the normal cell. Furthermore, compounds 3f, 3p, 3r were subjected to KM mice suffering from S-180 carcinoma subcutaneously, which possessed more potent than Fluorouracil, a typical anticancer drug used clinically. So we may conclude that the modification to the mother nucleus of shikonin via the methylation is an available approach to acquiring anti-tumor agents with higher selectivity and lower toxicity.
School of Pharmacy, Shanghai Jiaotong University, 800 Dongchuan Road, Shanghai 200240, China.
Wen
W
Zhou
Ying
Y
Peng
Shao-Shun
SS
Li
D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D015394:Molecular Structure; D009285:Naphthoquinones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D009285:Naphthoquinones; C016101:shikonin