Chemical synthesis and biological properties of pyridine epothilones. Academic Article uri icon

Overview

abstract

  • BACKGROUND: Numerous analogs of the antitumor agents epothilones A and B have been synthesized in search of better pharmacological profiles. Insights into the structure-activity relationships within the epothilone family are still needed and more potent and selective analogs of these compounds are in demand, both as biological tools and as chemotherapeutic agents, especially against drug-resistant tumors. RESULTS: A series of pyridine epothilone B analogs were designed, synthesized and screened. The synthesized compounds exhibited varying degrees of tubulin polymerization and cytotoxicity properties against a number of human cancer cell lines depending on the location of the nitrogen atom and the methyl substituent within the pyridine nucleus. CONCLUSIONS: The biological screening results in this study established the importance of the nitrogen atom at the ortho position as well as the beneficial effect of a methyl substituent at the 4- or 5-position of the pyridine ring. Two pyridine epothilone B analogs (i.e. compounds 3 and 4) possessing higher potencies against drug-resistant tumor cells than epothilone B, the most powerful of the naturally occurring epothilones, were identified.

publication date

  • August 1, 2000

Research

keywords

  • Antineoplastic Agents
  • Epothilones
  • Epoxy Compounds
  • Pyridines
  • Thiazoles

Identity

Scopus Document Identifier

  • 0033826818

Digital Object Identifier (DOI)

  • 10.1016/s1074-5521(00)00006-5

PubMed ID

  • 11048950

Additional Document Info

volume

  • 7

issue

  • 8