title: Synthesis and antitumour activity of β-hydroxyisovalerylshikonin analogues.
abstract: A series of novel β-hydroxyisovalerylshikonin analogues bearing oxygen-containing substituents at the side-chain hydroxyl of shikonin were designed and synthesized. The cytotoxicities of these compounds were evaluated in vitro against multi-drug resistant (MDR) cell lines DU-145 and HeLa. Most compounds exhibited significant inhibitory activity on both cell lines. The structure-activity relationship showed the analogues with ether substituents displayed the most potent antitumour activity and selective cytotoxicity towards DU-145. Among the compounds with ether substituents, increasing the steric hindrance in the carbon bearing β-hydroxyl or replace the β-hydroxyl with acetoxy or methoxy would lead to the decline of cytotoxicity.
authors.affiliation: School of Pharmacy, Shanghai Jiaotong University, 800 Dongchuan Road, 200240 Shanghai, China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Rao
authors.forename: Xin
authors.initials: X
authors.lastname: Liu
authors.forename: Wen
authors.initials: W
authors.lastname: Zhou
authors.forename: Jing
authors.initials: J
authors.lastname: Yi
authors.forename: Shao-Shun
authors.initials: SS
authors.lastname: Li
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002851:Chromatography, High Pressure Liquid; D006801:Humans; D013058:Mass Spectrometry; D009285:Naphthoquinones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D009285:Naphthoquinones; C118460:beta-hydroxyisovalerylshikonin