title: Synthesis and in vitro antitumor activity of asperphenamate derivatives as autophagy inducer.
abstract: In an effort to improve the aqueous solubility and the antitumor activity of natural product asperphenamate, we have designed and synthesized three series of asperphenamate derivatives, including series I (simplifying molecular skeleton series), series II (introducing a hydroxyl group to A-phenyl ring series) and series III (disrupting molecular planarity series). All derivatives have displayed a significantly increased solubility compared with asperphenamate. Their growth inhibitory activities in vitro were screened by the standard MTT method in MCF-7, HeLa, and BEL-7402 cell lines. With the exception of the derivatives in series I, most of derivatives in series II and series III showed growth inhibitory activity. Among all derivatives, IM23b in series III showed the greatest potency in human breast cancer MCF-7 cells. The cellular potency of IM23b was approximately 1.5-fold more potent than that of cisplatin. The mechanism of cell death induced by IM23b in human breast cancer MCF-7 cells was further investigated. We concluded that the cell death was induced by autophagy instead of apoptosis or cell cycle arrest.
authors.affiliation: School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, Shenyang, PR China.
authors.forename: Lei
authors.initials: L
authors.lastname: Yuan
authors.forename: Yanchun
authors.initials: Y
authors.lastname: Li
authors.forename: Chunyang
authors.initials: C
authors.lastname: Zou
authors.forename: Chao
authors.initials: C
authors.lastname: Wang
authors.forename: Jian
authors.initials: J
authors.lastname: Gao
authors.forename: Caixia
authors.initials: C
authors.lastname: Miao
authors.forename: Enlong
authors.initials: E
authors.lastname: Ma
authors.forename: Tiemin
authors.initials: T
authors.lastname: Sun
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D001343:Autophagy / Q000187:drug effects*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D005260:Female; D006801:Humans; D010649:Phenylalanine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D012995:Solubility; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D010649:Phenylalanine; C014343:asperphenamate; D002945:Cisplatin