Synthesis and evaluation of the apoptosis inducing and CT DNA interaction properties of a series of 4β-carbamoyl 4'-O-demethylepipodophyllotoxins.

Abstract

A series of carbamate derivatives of 4'-demethylepipodophyllotoxin have been synthesized, and their cytotoxicities against several human cancer cell lines, including HeLa, A549, HCT-8, and HL-60 cells, evaluated. Some of these compounds exhibited higher levels of cytotoxicity than the anticancer drug etoposide. 4β-4'-Demethylepipodophyllotoxin 1-(4-nitrophenyl) piperazinyl carbamate (19) was found to be the most potent compound of those synthesized in the current study, and induced cell cycle arrest in the G2/M phase in HeLa cells, which was accompanied by apoptosis. Furthermore, this compound activated the expression of Bax, p53 and caspase-3 in HeLa cells, leading to changes in the conformation of calf thymus DNA from the B-form to a more compact C-form.

• Authors: Chun-Yan Sang, Jian-Fei Liu, Wen-Wen Qin, Jie Zhao, Lin Hui, Yong-Xin Jin, Shi-Wu Chen
• Journal: European journal of medicinal chemistry (Eur J Med Chem) Vol. 70 Pg. 59-67 ( 2013) ISSN: 1768-3254 [Electronic] France
• PMID: 24140948 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 Elsevier Masson SAS. All rights reserved.

Chemical References

• Antineoplastic Agents
• Carbamates
• DNA
• calf thymus DNA

Topics

• Animals
• Antineoplastic Agents (chemical synthesis, chemistry, pharmacology)
• Apoptosis (drug effects)
• Carbamates (chemical synthesis, chemistry, pharmacology)
• Cattle
• Cell Cycle (drug effects)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• DNA (chemistry)
• Dose-Response Relationship, Drug
• Drug Screening Assays, Antitumor
• HL-60 Cells
• HeLa Cells
• Humans
• Molecular Structure
• Structure-Activity Relationship