title: Design and synthesis of novel 4'-demethyl-4-deoxypodophyllotoxin derivatives as potential anticancer agents.
abstract: A group of podophyllotoxin (PPT) derivatives (7a-j) were synthesized by conjugating aryloxyacetanilide moieties to the 4'-hydroxyl of 4'-demethyl-4-deoxypodophyllotoxin (DDPT), and their anticancer activity was evaluated. It was found that the most potent compound 7d inhibited the proliferation of three cancer cell lines with sub to low micromolar IC50 values. Furthermore, it was demonstrated that 7d induced cell cycle arrest in G2/M phase in MGC-803 cells, and regulated the expression of cell cycle check point proteins, such as cyclin A, cyclin B, CDK1, cdc25c, and p21. Finally, 4 mg/kg of 7d reduced the weights and volumes of HepG2 xenografts in mice. Our findings suggest that 7d might be a potential anticancer agent.
authors.affiliation: Medicinal and Chemical Institute, China Pharmaceutical University, Nanjing 210009, PR China.
authors.forename: Xiong
authors.initials: X
authors.lastname: Zhu
authors.affiliation: Department of Medicinal Chemistry, University of Florida, Gainesville, FL 32610, United States.
authors.forename: Junjie
authors.initials: J
authors.lastname: Fu
authors.affiliation: Medicinal and Chemical Institute, China Pharmaceutical University, Nanjing 210009, PR China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Tang
authors.affiliation: State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Carcinogenesis and Intervention, China Pharmaceutical University, Nanjing 210009, PR China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Gao
authors.affiliation: Medicinal and Chemical Institute, China Pharmaceutical University, Nanjing 210009, PR China.
authors.forename: Shijin
authors.initials: S
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Carcinogenesis and Intervention, China Pharmaceutical University, Nanjing 210009, PR China. Electronic address: anticancer_drug@163.com.
authors.forename: Qinglong
authors.initials: Q
authors.lastname: Guo
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology / Q000627:therapeutic use; D018797:Cell Cycle Proteins / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D015195:Drug Design; D004365:Drugs, Chinese Herbal; D059565:G2 Phase Cell Cycle Checkpoints / Q000187:drug effects; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy; D059566:M Phase Cell Cycle Checkpoints / Q000187:drug effects; D051379:Mice; D008819:Mice, Nude; D011034:Podophyllotoxin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D014183:Transplantation, Heterologous
chemical_list: D000970:Antineoplastic Agents; D018797:Cell Cycle Proteins; D004365:Drugs, Chinese Herbal; C014451:deoxypodophyllotoxin; D011034:Podophyllotoxin
keywords: Anticancer; Aryloxyacetanilide; Cell cycle; Cyclin; Podophyllotoxin