title: Synthesis, in vitro and in vivo antitumor activity of scopoletin-cinnamic acid hybrids.
abstract: A series of hybrids of scopoletin and substituted cinnamic acid were designed, synthesized and evaluated in vitro and in vivo against five human tumor cell lines [MCF-7, MDA-MB-231, A549, HCT-116, and HeLa] with doxorubicin as the positive control. Compounds 17a, 17b, 17c and 17g exhibited potent cytotoxic activity. Especially, compound 17b displayed broad spectrum activity with IC50 values ranging from 0.249 μM to 0.684 μM. Moreover, in a preliminary pharmacological study, 17b not only remarkably induced cellular apoptosis, but also clearly induced A549 cells cycle arrest at S phase. In vivo study showed that 17b significantly suppressed tumor growth in a dose-dependent manner without causing the loss of the mean body weight of mice, which was superior to doxorubicin. These preliminary results indicate that 17b is an optimal anti-cancer leading compound and merit further structural modification.
authors.affiliation: Department of Natural Medicinal Chemistry, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, People's Republic of China.
authors.forename: Linhu
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Pharmacology of Chinese Materia Medica, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, People's Republic of China.
authors.forename: Peng
authors.initials: P
authors.lastname: Zhao
authors.affiliation: Department of Natural Medicinal Chemistry, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, People's Republic of China.
authors.forename: Jinglin
authors.initials: J
authors.lastname: Hu
authors.affiliation: Department of Natural Medicinal Chemistry, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, People's Republic of China.
authors.forename: Jinhong
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Natural Medicinal Chemistry, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, People's Republic of China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Natural Medicinal Chemistry, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, People's Republic of China.
authors.forename: Zhiqiang
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Chinese Materia Medica Analysis, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, People's Republic of China. Electronic address: yfxiacpu@126.com.
authors.forename: Yufeng
authors.initials: Y
authors.lastname: Xia
authors.affiliation: Department of Pharmacology of Chinese Materia Medica, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, People's Republic of China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Dai
authors.affiliation: Department of Natural Medicinal Chemistry, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, People's Republic of China. Electronic address: chenliduo12@gmail.com.
authors.forename: Li
authors.initials: L
authors.lastname: Chen
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D060326:Chemistry Techniques, Synthetic; D002934:Cinnamates / Q000737:chemistry*; D005260:Female; D006801:Humans; D051379:Mice; D012603:Scopoletin / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D002934:Cinnamates; C029010:cinnamic acid; D012603:Scopoletin
keywords: Antitumor activity; Cinnamic acid; Scopoletin