Synthesis and evaluation of mansonone F derivatives as topoisomerase inhibitors

Eur J Med Chem. 2011 Aug;46(8):3339-47. doi: 10.1016/j.ejmech.2011.04.059. Epub 2011 May 5.

Abstract

A series of mansonone F (MF) derivatives were designed and synthesized. These compounds were found to be strong inhibitors for topoisomerases, with much more significant inhibition for topoisomerase II rather than topoisomerase I. The best inhibitor showed 20 times stronger anti-topoisomerase II activity than a positive control Etoposide. The cytotoxic activity of these MF derivatives was evaluated against human cancer cell lines CNE-2 and Glc-82, which showed that these compounds were potent antitumor agents. The structure-activity relationships (SARs) study revealed that o-quinone group and pyran ring are important for their cytotoxic activity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / drug therapy*
  • Adenocarcinoma / enzymology
  • Adenocarcinoma / pathology
  • Adenocarcinoma of Lung
  • Antigens, Neoplasm / metabolism*
  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / pharmacology
  • Carcinoma
  • Cell Line, Tumor
  • Cell Survival / drug effects*
  • DNA / chemistry
  • DNA / metabolism
  • DNA Topoisomerases, Type I / metabolism*
  • DNA Topoisomerases, Type II / metabolism*
  • DNA-Binding Proteins / metabolism*
  • Drug Screening Assays, Antitumor
  • Etoposide / pharmacology
  • Humans
  • Inhibitory Concentration 50
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / enzymology
  • Lung Neoplasms / pathology
  • Naphthoquinones / chemical synthesis*
  • Naphthoquinones / pharmacology
  • Nasopharyngeal Carcinoma
  • Nasopharyngeal Neoplasms / drug therapy*
  • Nasopharyngeal Neoplasms / enzymology
  • Nasopharyngeal Neoplasms / pathology
  • Plasmids / chemistry
  • Plasmids / metabolism
  • Pyrans / chemistry
  • Quinones / chemistry
  • Sesquiterpenes / chemical synthesis*
  • Sesquiterpenes / pharmacology
  • Structure-Activity Relationship
  • Telomerase / antagonists & inhibitors
  • Telomerase / metabolism
  • Topoisomerase Inhibitors / chemical synthesis*
  • Topoisomerase Inhibitors / pharmacology

Substances

  • Antigens, Neoplasm
  • Antineoplastic Agents
  • DNA-Binding Proteins
  • Naphthoquinones
  • Pyrans
  • Quinones
  • Sesquiterpenes
  • Topoisomerase Inhibitors
  • mansonone F
  • Etoposide
  • DNA
  • Telomerase
  • DNA Topoisomerases, Type I
  • TOP1 protein, human
  • DNA Topoisomerases, Type II