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: Shi-Wu Chen, Yuan-Yu Gao, Ni-Ni Zhou, Jie Liu, Wen-Ting Huang, Ling Hui, Yan Jin, Yong-Xin Jin
• Journal: Bioorganic & medicinal chemistry letters (Bioorg Med Chem Lett) Vol. 21 Issue 24 Pg. 7355-8 (Dec 15 2011) ISSN: 1464-3405 [Electronic] England
• PMID: 22041063 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 Elsevier Ltd. All rights reserved.

Chemical References

• 4'-demethyldesoxypodophyllotoxin
• Antineoplastic Agents
• Carbamates
• Podophyllotoxin

Topics

• Antineoplastic Agents (chemical synthesis, chemistry, pharmacology, toxicity)
• Carbamates (chemical synthesis, chemistry, pharmacology, 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 (analogs & derivatives, chemistry)