title: Synthesis and biological evaluation of a novel artesunate-podophyllotoxin conjugate as anticancer agent.
abstract: A novel conjugate of artesunate-podophyllotoxin was prepared and evaluated for its cytotoxicity against diverse normal and multidrug resistance human cancer cell lines by CCK-8 assay. The conjugate exhibited good cytotoxicity on all the cell lines with IC50 values of 0.453±0.156-3.011±0.272μM and reduced the resistant factor. The conjugate was further found to disrupt the microtubule network and induce G2/M cell cycle arrest in multidrug resistance K562/ADR cells. Meanwhile, Hoechst staining analysis suggested that conjugate induced cell death by apoptosis. Furthermore, conjugate could downregulate the levels of P-glycoprotein (P-gp) in P-gp overexpressing K562/ADR cells.
authors.affiliation: School of Pharmacy, Zunyi Medical University, 201 Dalian Road, Zunyi 563003, PR China. Electronic address: lzhang@zmc.edu.cn.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
authors.affiliation: School of Pharmacy, Zunyi Medical University, 201 Dalian Road, Zunyi 563003, PR China.
authors.forename: Fan
authors.initials: F
authors.lastname: Chen
authors.affiliation: School of Pharmacy, Zunyi Medical University, 201 Dalian Road, Zunyi 563003, PR China.
authors.forename: Zeguo
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: School of Pharmacy, Zunyi Medical University, 201 Dalian Road, Zunyi 563003, PR China.
authors.forename: Yongzheng
authors.initials: Y
authors.lastname: Chen
authors.affiliation: School of Pharmacy, Zunyi Medical University, 201 Dalian Road, Zunyi 563003, PR China. Electronic address: wangjing@zmc.edu.cn.
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D037621:Artemisinins / Q000737:chemistry* / Q000494:pharmacology*; D000077332:Artesunate; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D018432:Drug Resistance, Multiple / Q000187:drug effects*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D020014:K562 Cells; D015394:Molecular Structure; D011034:Podophyllotoxin / Q000737:chemistry* / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D037621:Artemisinins; D000077332:Artesunate; D011034:Podophyllotoxin
keywords: Apoptosis; Artesunate; Cell cycle; Cytotoxicity; Microtubule; Podophyllotoxin