title: Novel N-Substituted 2-(2-(Adamantan-1-yl)-1H-Indol-3-yl)-2-Oxoacetamide Derivatives: Synthesis and Biological Evaluation.
abstract: In this study, a series of novel N-substituted 2-(2-(adamantan-1-yl)-1H-indol-3-yl)-2-oxoacetamide derivatives were synthesized, and evaluated for their cytotoxicity in human cell lines including Hela (cervical cancer), MCF7 (breast cancer ) and HepG2 (liver cancer). Several compounds were found to have potent anti-proliferative activity against those human cancer cell lines and compound 5r showed the most potent biological activity against HepG2 cells with an IC50 value of 10.56 ± 1.14 μΜ. In addition, bioassays showed that compound 5r induced time-dependent and dose-dependent cleavage of poly ADP-ribose polymerase (PARP), and also induced a dose-dependent increase in caspase-3 and caspase-8 activity, but had little effect on caspase-9 protease activity in HepG2 cells. These results provide evidence that 5r-induced apoptosis in HepG2 cell is caspase-8-dependent.
authors.affiliation: School of Pharmaceutical Sciences and the Key Laboratory for Chemical Biology of Fujian Province, Xiamen University, South Xiang-An Road, Xiamen 361102, China. huhongyu22@126.com.
authors.forename: Hong-Yu
authors.initials: HY
authors.lastname: Hu
authors.affiliation: School of Pharmaceutical Sciences and the Key Laboratory for Chemical Biology of Fujian Province, Xiamen University, South Xiang-An Road, Xiamen 361102, China. yuxudong91@163.com.
authors.forename: Xu-Dong
authors.initials: XD
authors.lastname: Yu
authors.affiliation: School of Pharmaceutical Sciences and the Key Laboratory for Chemical Biology of Fujian Province, Xiamen University, South Xiang-An Road, Xiamen 361102, China. tjdxwangfei@163.com.
authors.forename: Fei
authors.initials: F
authors.lastname: Wang
authors.affiliation: School of Pharmaceutical Sciences and the Key Laboratory for Chemical Biology of Fujian Province, Xiamen University, South Xiang-An Road, Xiamen 361102, China. reyiai@163.com.
authors.forename: Chun-Rong
authors.initials: CR
authors.lastname: Lin
authors.affiliation: School of Pharmaceutical Sciences and the Key Laboratory for Chemical Biology of Fujian Province, Xiamen University, South Xiang-An Road, Xiamen 361102, China. jzzeng@xmu.edu.cn.
authors.forename: Jin-Zhang
authors.initials: JZ
authors.lastname: Zeng
authors.affiliation: School of Pharmaceutical Sciences and the Key Laboratory for Chemical Biology of Fujian Province, Xiamen University, South Xiang-An Road, Xiamen 361102, China. qyk@xmu.edu.cn.
authors.forename: Ying-Kun
authors.initials: YK
authors.lastname: Qiu
authors.affiliation: School of Pharmaceutical Sciences and the Key Laboratory for Chemical Biology of Fujian Province, Xiamen University, South Xiang-An Road, Xiamen 361102, China. fangmj@xmu.edu.cn.
authors.forename: Mei-Juan
authors.initials: MJ
authors.lastname: Fang
authors.affiliation: School of Pharmaceutical Sciences and the Key Laboratory for Chemical Biology of Fujian Province, Xiamen University, South Xiang-An Road, Xiamen 361102, China. wuzhen@xmu.edu.cn.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Wu
mesh_terms: D000081:Acetamides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D020169:Caspases / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006367:HeLa Cells; D056945:Hep G2 Cells; D006801:Humans; D061986:MCF-7 Cells; D015394:Molecular Structure; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism
chemical_list: D000081:Acetamides; D000970:Antineoplastic Agents; D011065:Poly(ADP-ribose) Polymerases; D020169:Caspases
keywords: 2-(2-(adamantan-1-yl)-1H-indol-3-yl)-2-oxoacetamidederivatives; apoptosis; caspase-8; poly ADP-ribose polymerase (PARP)