Vacuolar-type H(+)-ATPase inhibitory activity of synthetic analogues of the concanamycins: is the hydrogen bond network involving the lactone carbonyl, the hemiacetal hydroxy group, and the C-19 hydroxy group essential for the biological activity of the concanamycins?

Bioorg Med Chem Lett. 2002 Dec 16;12(24):3525-8. doi: 10.1016/s0960-894x(02)00806-5.

Abstract

Synthetic analogue of the concanamycins, which lacks the hydrogen bond network existing in the concanamycin structure, retains vacuolar-type H(+)-ATPase (V-ATPase) inhibitory activity and induces apoptosis to cancer cells that overexpressing epidermal growth factor receptors (EGFR).

MeSH terms

  • Anti-Bacterial Agents / chemistry*
  • Anti-Bacterial Agents / pharmacology*
  • Apoptosis / drug effects
  • Cell Survival / drug effects
  • Dose-Response Relationship, Drug
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology
  • Epidermal Growth Factor / pharmacology
  • ErbB Receptors / physiology
  • Humans
  • Hydrogen Bonding
  • Hydrogen-Ion Concentration
  • Macrolides*
  • Neoplasm Proteins
  • Structure-Activity Relationship
  • Vacuolar Proton-Translocating ATPases / antagonists & inhibitors*

Substances

  • Anti-Bacterial Agents
  • Enzyme Inhibitors
  • Macrolides
  • Neoplasm Proteins
  • concanamycin F
  • Epidermal Growth Factor
  • ErbB Receptors
  • Vacuolar Proton-Translocating ATPases