Synthesis and structure-activity studies of the V-ATPase inhibitor saliphenylhalamide (SaliPhe) and simplified analogs

Bioorg Med Chem Lett. 2015 Oct 15;25(20):4393-8. doi: 10.1016/j.bmcl.2015.09.021. Epub 2015 Sep 8.

Abstract

An efficient total synthesis of the potent V-ATPase inhibitor saliphenylhalamide (SaliPhe), a synthetic variant of the natural product salicylihalamide A (SaliA), has been accomplished aimed at facilitating the development of SaliPhe as an anticancer and antiviral agent. This new approach enabled facile access to derivatives for structure-activity relationship studies, leading to simplified analogs that maintain SaliPhe's biological properties. These studies will provide a solid foundation for the continued evaluation of SaliPhe and analogs as potential anticancer and antiviral agents.

Keywords: Anticancer; Antiviral; Benzolactone; Salicylihalamide; V-ATPase.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amides / chemical synthesis
  • Amides / chemistry
  • Amides / pharmacology*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Dose-Response Relationship, Drug
  • Enzyme Inhibitors / chemical synthesis
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology*
  • Humans
  • Molecular Structure
  • Salicylates / chemical synthesis
  • Salicylates / chemistry
  • Salicylates / pharmacology*
  • Structure-Activity Relationship
  • Vacuolar Proton-Translocating ATPases / antagonists & inhibitors*
  • Vacuolar Proton-Translocating ATPases / metabolism

Substances

  • Amides
  • Enzyme Inhibitors
  • Salicylates
  • saliphenylhalamide
  • Vacuolar Proton-Translocating ATPases