title: Design, synthesis and anticancer activities of novel otobain derivatives.
abstract: A series of novel racemic otobain derivatives was designed and synthesised using 2-piperonyl-1,3-dithianes in the conjugate addition-alkylation to 5H-furan-2-one, followed by cationic cyclisation. All the synthesised compounds were consequently evaluated for their anticancer activity against several human cancers in vitro. The efficacy of the most active compound 27g was comparable with etoposide, with IC50 values ranging from 1.06 μM to 4.16 μM in different cancer cell lines. Notably, compound 27g strongly induced cell cycle arrest and increased the expression of mitosis-specific markers MPM-2 and phosphorylated histone H3, but it did not trigger cell apoptosis. Further a colony formation assay showed that compound 27g effectively inhibited the anchor growth of lung cancer cells in a dose-dependent manner. More importantly, compound 27g at 40 mg kg(-1) significantly suppressed tumour volume (P < 0.01) and tumour weight (P < 0.05) in a human lung cancer cell xenograft mouse model without causing systematic toxicity in mice. Our findings indicated that compound 27g has significant potential for further drug development.
authors.affiliation: Department of Chemistry, School of Chemistry and Molecular Engineering, East China Normal University, 500 Dongchuan Road, Shanghai 200241, China. xzzou@chem.ecnu.edu.cn.
authors.forename: Zhongzhou
authors.initials: Z
authors.lastname: Li
authors.affiliation: Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai 200241, China. xfpang@bio.ecnu.edu.cn.
authors.forename: Hui
authors.initials: H
authors.lastname: Su
authors.affiliation: Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai 200241, China. xfpang@bio.ecnu.edu.cn.
authors.forename: Weiwei
authors.initials: W
authors.lastname: Yu
authors.affiliation: Department of Chemistry, School of Chemistry and Molecular Engineering, East China Normal University, 500 Dongchuan Road, Shanghai 200241, China. xzzou@chem.ecnu.edu.cn.
authors.forename: Xinjun
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Chemistry, School of Chemistry and Molecular Engineering, East China Normal University, 500 Dongchuan Road, Shanghai 200241, China. xzzou@chem.ecnu.edu.cn.
authors.forename: Hao
authors.initials: H
authors.lastname: Cheng
authors.affiliation: Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai 200241, China. xfpang@bio.ecnu.edu.cn.
authors.forename: Mingyao
authors.initials: M
authors.lastname: Liu
authors.affiliation: Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai 200241, China. xfpang@bio.ecnu.edu.cn.
authors.forename: Xiufeng
authors.initials: X
authors.lastname: Pang
authors.affiliation: Department of Chemistry, School of Chemistry and Molecular Engineering, East China Normal University, 500 Dongchuan Road, Shanghai 200241, China. xzzou@chem.ecnu.edu.cn.
authors.forename: Xinzhuo
authors.initials: X
authors.lastname: Zou
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; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D018360:Crystallography, X-Ray; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D017705:Lignans / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008958:Models, Molecular; D015394:Molecular Structure; D009374:Neoplasms, Experimental / Q000188:drug therapy / Q000473:pathology; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D017705:Lignans; C000610866:otobain