title: Antitumor activities of biscoumarin and dihydropyran derivatives.
abstract: Rising worldwide cancer incidence and resistance to current anti-cancer drugs necessitate the need for new pharmaceutical compounds and drug delivery system. Two novel series of biscoumarin (1-4) and dihydropyran (5-16) derivatives were synthesized via a one-pot multicomponent condensation reaction and evaluated for their antitumor activity in vitro. The X-ray crystal structure analysis of four representative compounds 2, 7, 10 and 13 confirmed the structures of these compounds. Compounds 1-4 showed the most potent antitumor activity among the total 16 derivatives. More interestingly, preliminary mechanism studies revealed that the most potent compound 4 induced apoptosis and arrested the cell cycle at the S phase in HUTU80 cells. Additionally, the increased accumulation of HUTU80 cells in the sub G1 peak further pointed to the occurence of the cell apoptosis. The selectivity index analysis demonstrated that all the biscoumarin compounds (SI=3.1-7.5) possess higher selectivity towards intestinal epithelial adenocarcinoma cell line (HuTu80) than positive control drug carboplatin (SI=1.6-1.8). The biscoumarin compounds also showed no obvious acute toxicity on mice.
authors.affiliation: Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China.
authors.forename: Hai-Yu
authors.initials: HY
authors.lastname: Zhou
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325035, China.
authors.forename: Feng-Quan
authors.initials: FQ
authors.lastname: Dong
authors.affiliation: Graduate School of China Academy of Chinese Medical Sciences, Beijing 100700, China.
authors.forename: Xin-Liang
authors.initials: XL
authors.lastname: Du
authors.affiliation: Department of Pharmacy, Guangdong Medical College, Dong guan 523808, China.
authors.forename: Zhi-Kun
authors.initials: ZK
authors.lastname: Zhou
authors.affiliation: Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China.
authors.forename: Hai-Ru
authors.initials: HR
authors.lastname: Huo
authors.affiliation: Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China.
authors.forename: Wei-Hao
authors.initials: WH
authors.lastname: Wang
authors.affiliation: Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China.
authors.forename: Hong-Dan
authors.initials: HD
authors.lastname: Zhan
authors.affiliation: Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China.
authors.forename: Yi-Fei
authors.initials: YF
authors.lastname: Dai
authors.affiliation: Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China.
authors.lastname: Jing Meng
authors.affiliation: Department of Neurology, Bejing Tiantan Hospital, Capital Medical University, Beijing 100050, China.
authors.forename: Yun-Peng
authors.initials: YP
authors.lastname: Sui
authors.affiliation: School of Chemical Engineering, The Key Laboratory for Surface Engineering and Remanufacturing in Shaanxi Province, Xi'an University, Xi'an 710065, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Li
authors.affiliation: Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China. Electronic address: fsui@icmm.ac.cn.
authors.forename: Feng
authors.initials: F
authors.lastname: Sui
authors.affiliation: School of Chemical Engineering, The Key Laboratory for Surface Engineering and Remanufacturing in Shaanxi Province, Xi'an University, Xi'an 710065, China. Electronic address: Yunhui_zhai66@yeah.net.
authors.forename: Yun-Hui
authors.initials: YH
authors.lastname: Zhai
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D003374:Coumarins / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D018360:Crystallography, X-Ray; D004354:Drug Screening Assays, Antitumor; D059585:G1 Phase Cell Cycle Checkpoints / Q000187:drug effects; D057809:HEK293 Cells; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D007668:Kidney / Q000187:drug effects / Q000473:pathology; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008968:Molecular Conformation; D011714:Pyrans / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D003374:Coumarins; D011714:Pyrans
keywords: Acute toxicity; Antitumor; Apoptosis; Biscoumarin; Dihydropyran; X-ray