title: Design, synthesis and biological evaluation of novel asperphenamate derivatives.
abstract: A series of novel asperphenamate derivatives were designed and synthesized, including series I (the A-phenyl group replaced with various aromatic heterocycles) and series II (the acyl group substituted by sulfonyl group). All compounds have been screened for their antiproliferative activity in vitro against MCF-7, HeLa, and BEL-7402 cell lines by the standard MTT method. Structure-activity relationship studies displayed the heterocycle type played an important role in activity. Six-membered ring derivatives displayed more potency than five-membered ring and the sulfonyl group in A-ring region made an important contribution to activity. Among all derivatives, tosyl derivative 8c exhibited the greatest potency in three human cancer cell lines. Especially in MCF-7 cells, the cellular potency of 8c was approximately 3.0-fold more potent than that of cisplatin. Firstly, the mechanism of cell death induced by 8c in MCF-7 cells was investigated. The results showed that the cell death was induced by autophagy instead of apoptosis or cell cycle arrest. Further studies indicated that 8c might induce autophagic cell death in HeLa and BEL-7402 cell lines.
authors.affiliation: Key Laboratory of Structure-Based Drug Design and Discovery (Shenyang Pharmaceutical University), Ministry of Education, Shenyang 110016, PR China.
authors.forename: Qingyin
authors.initials: Q
authors.lastname: Liu
authors.affiliation: Department of Neurology, General Hospital of Shenyang Military Command, Shenyang 110840, PR China.
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.affiliation: Key Laboratory of Structure-Based Drug Design and Discovery (Shenyang Pharmaceutical University), Ministry of Education, Shenyang 110016, PR China.
authors.forename: Lei
authors.initials: L
authors.lastname: Sheng
authors.affiliation: Department of Pharmacy, Liaoning Vocational College of Medicine, Shenyang 110101, PR China.
authors.forename: Chunyang
authors.initials: C
authors.lastname: Zou
authors.affiliation: Key Laboratory of Structure-Based Drug Design and Discovery (Shenyang Pharmaceutical University), Ministry of Education, Shenyang 110016, PR China.
authors.forename: Hongxin
authors.initials: H
authors.lastname: Sun
authors.affiliation: Key Laboratory of Structure-Based Drug Design and Discovery (Shenyang Pharmaceutical University), Ministry of Education, Shenyang 110016, PR China.
authors.forename: Chunfeng
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Structure-Based Drug Design and Discovery (Shenyang Pharmaceutical University), Ministry of Education, Shenyang 110016, PR China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Key Laboratory of Structure-Based Drug Design and Discovery (Shenyang Pharmaceutical University), Ministry of Education, Shenyang 110016, PR China.
authors.forename: Jiyue
authors.initials: J
authors.lastname: Shi
authors.affiliation: Department of Pharmacology, Shenyang Pharmaceutical University, Shenyang 110016, PR China. Electronic address: enlongma@hotmail.com.
authors.forename: Enlong
authors.initials: E
authors.lastname: Ma
authors.affiliation: Key Laboratory of Structure-Based Drug Design and Discovery (Shenyang Pharmaceutical University), Ministry of Education, Shenyang 110016, PR China. Electronic address: yuanlei3094@163.com.
authors.forename: Lei
authors.initials: L
authors.lastname: Yuan
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D001343:Autophagy / Q000187:drug effects*; D045744:Cell Line, Tumor; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D006367:HeLa Cells; D006801:Humans; D061986:MCF-7 Cells; D009369:Neoplasms / Q000188:drug therapy / Q000473:pathology; D010649:Phenylalanine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D010649:Phenylalanine; C014343:asperphenamate
keywords: Anticancer activity; Asperphenamate; Dipeptide analog; Inducing autophagy; Structure–activity relationship; Synthesis