title: Synthesis and evaluation of novel isoxazolyl chalcones as potential anticancer agents.
abstract: A series of novel isoxazolyl chalcones were synthesized and evaluated for their activities in vitro against four types of human non-small cell lung cancer cells, including H1792, H157, A549 and Calu-1 cells. The preliminary biological screening showed that compounds 5d and 5f-i exhibited significant cytotoxicity, particularly, compounds 5f and 5h were identified as the most potent anticancer agents with IC50 values 1.35-2.07 μM and 7.27-11.07 μM against H175, A549 and Calu-1 cell lines, respectively. Compounds 5f-i could induce apoptosis in A549 cells by death receptor 5 (DR5) mediated extrinsicpathways. The preliminary structure-activity relationship study showed that compounds bearing electron withdrawing groups (EWG) at the 2-position of the phenyl ring in Ar group were more effective than those with EWG at 4-position. These results further demonstrated that the scaffolds designed in this work might lead to the discovery of novel anti-lung cancer agents.
authors.affiliation: School of Chemistry and Chemical Engineering, Shandong University, Jinan, Shandong 250100, China.
authors.forename: Maosheng
authors.initials: M
authors.lastname: Wan
authors.affiliation: School of Life Sciences, Shandong University, Jinan, Shandong 250100, China.
authors.forename: Linyan
authors.initials: L
authors.lastname: Xu
authors.affiliation: Shandong Drug and Food Vocational College, Weihai, Shandong 264210, China.
authors.forename: Li
authors.initials: L
authors.lastname: Hua
authors.affiliation: Shandong Drug and Food Vocational College, Weihai, Shandong 264210, China.
authors.forename: Ailing
authors.initials: A
authors.lastname: Li
authors.affiliation: Shandong Drug and Food Vocational College, Weihai, Shandong 264210, China.
authors.forename: Shuqing
authors.initials: S
authors.lastname: Li
authors.affiliation: School of Chemistry and Chemical Engineering, Shandong University, Jinan, Shandong 250100, China.
authors.forename: Wenjing
authors.initials: W
authors.lastname: Lu
authors.affiliation: School of Chemistry and Chemical Engineering, Shandong University, Jinan, Shandong 250100, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Pang
authors.affiliation: School of Chemistry and Chemical Engineering, Shandong University, Jinan, Shandong 250100, China. Electronic address: cbcao@sdu.edu.cn.
authors.forename: Chengbo
authors.initials: C
authors.lastname: Cao
authors.affiliation: School of Life Sciences, Shandong University, Jinan, Shandong 250100, China.
authors.forename: Xiangguo
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Chemistry, Qilu Normal University, Jinan, Shandong 250013, China.
authors.forename: Peifu
authors.initials: P
authors.lastname: Jiao
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D047188:Chalcones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D007555:Isoxazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D047188:Chalcones; D007555:Isoxazoles
keywords: Apoptosis; Death receptor 5; Human non-small cell lung cancer cells; Isoxazolyl chalcones; Synthesis