Ceric ammonium nitrate-promoted oxidative coupling reaction for the synthesis and evaluation of a series of anti-tumor amide anhydrovinblastine analogs.

Abstract

A new, practical and efficient method for the synthesis of anhydrovinblastine AVBL (1f) by oxidative coupling of vindoline and catharanthine in the presence of ceric ammonium nitrate (CAN) was developed. Under the optimized reaction conditions, we synthesized a new series of amide anhydrovinblastine analogs substituted at the vindoline moiety of C-23 site and, evaluated for their proliferation inhibition against HeLa cell. The aryl-substituted derivatives showed loss of potency, while alkyl-substituted derivatives retained some of its cytotoxic potency. The iso-butylamide compound 10b and 2-furancorboxamide compound 18b displayed a similar cytotoxic potency compared to the positive control AVBL.

• Authors: Weibin Song, Min Lei, Kun Zhao, Lingjun Hu, Yuhui Meng, Dean Guo, Xuan Liu, Lihong Hu
• Journal: Bioorganic & medicinal chemistry letters (Bioorg Med Chem Lett) Vol. 22 Issue 1 Pg. 387-90 (Jan 01 2012) ISSN: 1464-3405 [Electronic] England
• PMID: 22115594 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 Elsevier Ltd. All rights reserved.

Chemical References

• Antineoplastic Agents
• Vinca Alkaloids
• Cerium
• Vinblastine
• Oxygen
• ceric ammonium nitrate

Topics

• Antineoplastic Agents (chemical synthesis, pharmacology)
• Binding Sites
• Cell Proliferation
• Cerium (chemistry, pharmacology)
• Chemistry, Pharmaceutical (methods)
• Circular Dichroism
• Drug Design
• Drug Screening Assays, Antitumor
• HeLa Cells
• Humans
• Hydrogen-Ion Concentration
• Inhibitory Concentration 50
• Models, Chemical
• Neoplasms (drug therapy)
• Oxygen (chemistry)
• Time Factors
• Vinblastine (analogs & derivatives)
• Vinca Alkaloids (chemistry)