Enhancement of drug affinity for cell membranes by conjugation with lipoamino acids. I. Synthesis and biological evaluation of lipophilic conjugates of tranylcypromine

Eur J Med Chem. 2005 Nov;40(11):1074-9. doi: 10.1016/j.ejmech.2005.05.009. Epub 2005 Aug 29.

Abstract

Conjugation with lipoamino acids (LAAs) increases the lipophilicity of drug molecules. Because of their amphipatic nature, they also provide the conjugated drugs a 'membrane-like character', capable to facilitate their interaction with and penetration through cell membranes and biological barriers. To study such a feature, our aim is to collect experimental and computational data using a novel series of lipophilic conjugates between a model drug (tranylcypromine (TCP)) and LAA residues containing a short, a medium or a long alkyl side chain (C-4 to C-16), to provide a wide range of lipophilicity. For comparison, a corresponding set of amides of TCP with alkanoic or fatty acids was prepared and characterized. Their in vitro monoamine oxidase inhibitory activity also tested.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acids / chemistry*
  • Amino Acids / pharmacology
  • Animals
  • Cell Membrane / metabolism*
  • Dose-Response Relationship, Drug
  • Drug Evaluation, Preclinical / methods
  • Drug Stability
  • Fatty Acids / chemistry
  • Lipids / chemistry*
  • Lipids / pharmacology
  • Liposomes / chemistry
  • Monoamine Oxidase Inhibitors / chemical synthesis
  • Monoamine Oxidase Inhibitors / pharmacology
  • Phospholipids / chemistry
  • Rats
  • Technology, Pharmaceutical
  • Tranylcypromine / chemistry*
  • Tranylcypromine / pharmacology

Substances

  • Amino Acids
  • Fatty Acids
  • Lipids
  • Liposomes
  • Monoamine Oxidase Inhibitors
  • Phospholipids
  • Tranylcypromine