title: Carbamates of 4'-demethyl-4-deoxypodophyllotoxin: synthesis, cytotoxicity and cell cycle effects.
abstract: In an attempt to generate compounds with superior bioactivity and reduced toxicity, 12 carbamates of 4'-demethyl-4-deoxypodophyllotoxin, N-(1-oxyl-4'-demethyl- 4-deoxypodophyllic)-α-amino acids amides, were synthesized and evaluated for antiproliferative activity and cell cycle effects. These synthesized compounds proved to be more hydrophilic, as well as improved or comparable in vitro cytotoxicities against four cell lines (A-549, HeLa, SiHa, and HL-60) compared with either parent DPT or anti-cancer drug VP-16. Furthermore, flow cytometric analysis exhibited that N-(1-oxyl-4'-demethyl-4-deoxypodophyllic)-d-α-methine amide (15f) induced cell cycle arrest in the G2/M phase in A-549 cells.
authors: School of Pharmacy, State Key Laboratory of Applied Organic Chemistry, Lanzhou University, Lanzhou 730000, China. chenshwu@gmail.com
authors: Shi-Wu
authors: SW
authors: Chen
authors: Yuan-Yu
authors: YY
authors: Gao
authors: Ni-Ni
authors: NN
authors: Zhou
authors: Jie
authors: J
authors: Liu
authors: Wen-Ting
authors: WT
authors: Huang
authors: Ling
authors: L
authors: Hui
authors: Yan
authors: Y
authors: Jin
authors: Yong-Xin
authors: YX
authors: Jin
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology / Q000633:toxicity; D002219:Carbamates / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology / Q000633:toxicity; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D059565:G2 Phase Cell Cycle Checkpoints; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D059566:M Phase Cell Cycle Checkpoints; D011034:Podophyllotoxin / Q000031:analogs & derivatives* / Q000737:chemistry
chemical_list: C508085:4'-demethyldesoxypodophyllotoxin; D000970:Antineoplastic Agents; D002219:Carbamates; D011034:Podophyllotoxin