title: Synthesis and biological evaluation of hydroxycinnamic acid hydrazide derivatives as inducer of caspase-3.
abstract: In order to generate compounds with superior antitumor activity and reduced toxicity, twelve new hydroxycinnamic acid hydrazide derivatives were synthesized and evaluated for their antiproliferative activities against two cancer cell lines (H1299 lung carcinoma cells and MCF-7 breast cancer cells), and compared to two normal counterparts (NL-20 lung epithelial cells and H184B5F5/M10 breast cells) by MTT method. The results demonstrated that some of these compounds possessed good antiproliferative activity against the two cancer cell lines. Among them, compound 2c was active against the growth of H1299 lung carcinoma cells with IC50 values of 1.50 μM, which was more active than the positive topotecan (IC50 = 4.18 μM). Simultaneously, it showed lower cytotoxic effects on normal NL-20 lung epithelial cells (IC50 > 10 μM). Mechanism studies indicated that it induced cell cycle arrest at G2/M phase followed by activation of caspase-3, and consequently caused the cell death. Further studies on the structure optimization are ongoing.
authors.affiliation: School of Pharmaceutics, Lanzhou University, 222 Tian Shui South Road, Lanzhou 730000, People's Republic of China.
authors.forename: Zheng-Rong
authors.initials: ZR
authors.lastname: Wu
authors.affiliation: The First Hospital of Lanzhou University, Lanzhou 730000, People's Republic of China.
authors.forename: Jian
authors.initials: J
authors.lastname: Liu
authors.affiliation: School of Pharmaceutics, Lanzhou University, 222 Tian Shui South Road, Lanzhou 730000, People's Republic of China.
authors.forename: Jian-Ying
authors.initials: JY
authors.lastname: Li
authors.affiliation: School of Pharmaceutics, Lanzhou University, 222 Tian Shui South Road, Lanzhou 730000, People's Republic of China.
authors.forename: Li-Fang
authors.initials: LF
authors.lastname: Zheng
authors.affiliation: School of Pharmaceutics, Lanzhou University, 222 Tian Shui South Road, Lanzhou 730000, People's Republic of China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Li
authors.affiliation: School of Pharmaceutics, Lanzhou University, 222 Tian Shui South Road, Lanzhou 730000, People's Republic of China.
authors.forename: Xing
authors.initials: X
authors.lastname: Wang
authors.affiliation: Institute of Microbiology, School of Life Sciences, Lanzhou University, 222 Tian Shui South Road, Lanzhou 730000, People's Republic of China.
authors.forename: Qing-Jian
authors.initials: QJ
authors.lastname: Xie
authors.affiliation: School of Pharmaceutics, Lanzhou University, 222 Tian Shui South Road, Lanzhou 730000, People's Republic of China.
authors.forename: Ai-Xia
authors.initials: AX
authors.lastname: Wang
authors.affiliation: School of Pharmaceutics, Lanzhou University, 222 Tian Shui South Road, Lanzhou 730000, People's Republic of China.
authors.forename: Ying-Hui
authors.initials: YH
authors.lastname: Li
authors.affiliation: Institute of Microbiology, School of Life Sciences, Lanzhou University, 222 Tian Shui South Road, Lanzhou 730000, People's Republic of China.
authors.forename: Rong-Hui
authors.initials: RH
authors.lastname: Liu
authors.affiliation: School of Pharmaceutics, Lanzhou University, 222 Tian Shui South Road, Lanzhou 730000, People's Republic of China; Institute of Microbiology, School of Life Sciences, Lanzhou University, 222 Tian Shui South Road, Lanzhou 730000, People's Republic of China. Electronic address: lihy@lzu.edu.cn.
authors.forename: Hong-Yu
authors.initials: HY
authors.lastname: Li
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000096:biosynthesis*; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D060326:Chemistry Techniques, Synthetic; D003373:Coumaric Acids / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D004790:Enzyme Induction / Q000187:drug effects; D006801:Humans; D020128:Inhibitory Concentration 50
chemical_list: D000970:Antineoplastic Agents; D003373:Coumaric Acids; D053148:Caspase 3
keywords: Apoptosis; Caspase; Hydroxycinnamic acid hydrazide