1. Carbamates of 4'-demethyl-4-deoxypodophyllotoxin: synthesis, cytotoxicity and cell cycle effects.
- Author
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Chen SW, Gao YY, Zhou NN, Liu J, Huang WT, Hui L, Jin Y, and Jin YX
- Subjects
- Antineoplastic Agents chemistry, Antineoplastic Agents pharmacology, Antineoplastic Agents toxicity, Carbamates chemical synthesis, Carbamates pharmacology, Carbamates toxicity, Cell Cycle drug effects, Cell Line, Tumor, Cell Survival drug effects, Drug Screening Assays, Antitumor, G2 Phase Cell Cycle Checkpoints, Humans, Hydrophobic and Hydrophilic Interactions, M Phase Cell Cycle Checkpoints, Podophyllotoxin chemistry, Antineoplastic Agents chemical synthesis, Carbamates chemistry, Podophyllotoxin analogs & derivatives
- 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., (Copyright © 2011 Elsevier Ltd. All rights reserved.)
- Published
- 2011
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