title: Design and synthesis of fluoroacylshikonin as an anticancer agent.
abstract: A series of shikonin derivatives, selectively acylated by various fluorinated carboxylic acids at the side chain of shikonin, were synthesized and their anticancer activity evaluated, in which eight compounds are reported for the first time. Among all the compounds tested, compound showed the most potent anticancer activity against B16-F10 (malignant melanoma cells), MG63 (human osteosarcoma cells), and A549 (lung cancer cells) with IC50 0.39 ± 0.01, 0.72 ± 0.04 and 0.58 ± 0.02 µmol/L. Docking simulation of compound was carried out to position into a tubulin active site to determine the probable binding conformation. All the results suggested that compound may be a potential anticancer agent.
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing, People's Republic of China.
authors.forename: Wen-Yao
authors.initials: WY
authors.lastname: Kong
authors.forename: Xiao-Feng
authors.initials: XF
authors.lastname: Chen
authors.forename: Jing
authors.initials: J
authors.lastname: Shi
authors.forename: Shahla Karim
authors.initials: SK
authors.lastname: Baloch
authors.forename: Jin-Liang
authors.initials: JL
authors.lastname: Qi
authors.forename: Hai-Liang
authors.initials: HL
authors.lastname: Zhu
authors.forename: Xiao-Ming
authors.initials: XM
authors.lastname: Wang
authors.forename: Yong-Hua
authors.initials: YH
authors.lastname: Yang
mesh_terms: D000215:Acylation; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D002264:Carboxylic Acids / Q000737:chemistry; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D060326:Chemistry Techniques, Synthetic; D015195:Drug Design; D006801:Humans; D009285:Naphthoquinones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D055503:Protein Multimerization / Q000187:drug effects; D020836:Protein Structure, Quaternary; D013379:Substrate Specificity; D014404:Tubulin / Q000737:chemistry
chemical_list: D000970:Antineoplastic Agents; D002264:Carboxylic Acids; D009285:Naphthoquinones; D014404:Tubulin; C016101:shikonin
keywords: anticancer activity; fluoroacylshikonin; tubulin inhibitor