title: Synthesis, antitumor activity, and mechanism of action of 6-acrylic phenethyl ester-2-pyranone derivatives.
abstract: Based on the scaffolds of caffeic acid phenethyl ester (CAPE) as well as bioactive lactone-containing compounds, 6-acrylic phenethyl ester-2-pyranone derivatives were synthesized and evaluated against five tumor cell lines (HeLa, C6, MCF-7, A549, and HSC-2). Most of the new derivatives exhibited moderate to potent cytotoxic activity. Moreover, HeLa cell lines showed higher sensitivity to these compounds. In particular, compound showed potent cytotoxic activity (IC50 = 0.50-3.45 μM) against the five cell lines. Further investigation on the mechanism of action showed that induced apoptosis, arrested the cell cycle at G2/M phases in HeLa cells, and inhibited migration through disruption of the actin cytoskeleton. In addition, ADMET properties were also calculated in silico, and compound showed good ADMET properties with good absorption, low hepatotoxicity, and good solubility, and thus, could easily be bound to carrier proteins, without inhibition of CYP2D6. A structure-activity relationship (SAR) analysis indicated that compounds with ortho-substitution on the benzene ring exhibited obviously increased cytotoxic potency. This study indicated that compound is a promising compound as an antitumor agent.
authors: Research Center for Drug Discovery, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, People's Republic of China. junxu@biochemomes.com guqiong@mail.sysu.edu.cn.
authors: Sai
authors: S
authors: Fang
authors: Lei
authors: L
authors: Chen
authors: Miao
authors: M
authors: Yu
authors: Bao
authors: B
authors: Cheng
authors: Yongsheng
authors: Y
authors: Lin
authors: Susan L
authors: SL
authors: Morris-Natschke
authors: Kuo-Hsiung
authors: KH
authors: Lee
authors: Qiong
authors: Q
authors: Gu
authors: Jun
authors: J
authors: Xu
mesh_terms: D000199:Actins / Q000737:chemistry; D000970:Antineoplastic Agents / Q000737:chemistry*; D017209:Apoptosis; D002109:Caffeic Acids / Q000737:chemistry*; D002453:Cell Cycle; D045744:Cell Line, Tumor; D002465:Cell Movement; D003599:Cytoskeleton / Q000378:metabolism; D004952:Esters / Q000737:chemistry*; D006367:HeLa Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D061986:MCF-7 Cells; D008856:Microscopy, Fluorescence; D009361:Neoplasm Invasiveness; D010626:Phenylethyl Alcohol / Q000031:analogs & derivatives* / Q000737:chemistry; D011753:Pyrones / Q000138:chemical synthesis* / Q000737:chemistry; D012995:Solubility; D013329:Structure-Activity Relationship
chemical_list: C000599524:6-acrylic phenethyl ester-2-pyranone; D000199:Actins; D000970:Antineoplastic Agents; D002109:Caffeic Acids; D004952:Esters; D011753:Pyrones; C055494:caffeic acid phenethyl ester; D010626:Phenylethyl Alcohol