Highly suppressing wild-type HIV-1 and Y181C mutant HIV-1 strains by 10-chloromethyl-11-demethyl-12-oxo-calanolide A with druggable profile

J Med Chem. 2010 Feb 11;53(3):1397-401. doi: 10.1021/jm901653e.

Abstract

We herein report a new compound: 10-chloromethyl-11-demethyl-12-oxo-calanolide A (20, EC(50) = 7.4 nM, SI = 1417), which demonstrates a druggable profile with 32.7% oral bioavailability in rat, tolerated oral single dose toxicity in mice, and especially the feature of highly efficient suppression of the wild-type HIV-1 and Y181C mutant HIV-1 at an EC(50) = 7.4 nM and EC(50) = 0.46 nM, respectively.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-HIV Agents / chemical synthesis
  • Anti-HIV Agents / chemistry
  • Anti-HIV Agents / pharmacology*
  • Biological Availability
  • Brain / drug effects
  • Cell Line
  • Cell Survival / drug effects
  • HIV Infections / drug therapy*
  • HIV Infections / genetics
  • HIV-1 / drug effects*
  • HIV-1 / genetics*
  • Inhibitory Concentration 50
  • Mice
  • Models, Molecular
  • Molecular Structure
  • Mutation / genetics
  • Pyranocoumarins / chemical synthesis
  • Pyranocoumarins / chemistry
  • Pyranocoumarins / pharmacology*
  • Rats
  • Structure-Activity Relationship
  • Virus Replication / drug effects*
  • Virus Replication / genetics

Substances

  • 10-chloromethyl-11-demethyl-12-oxocalanolide A
  • Anti-HIV Agents
  • Pyranocoumarins