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

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....

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Bibliographic Details
Published in:European journal of medicinal chemistry 2005-11, Vol.40 (11), p.1074-1079
Main Authors: Pignatello, Rosario, Puleo, Antonina, Guccione, Salvatore, Raciti, Giuseppina, Acquaviva, Rosaria, Campisi, Agatina, Ventura, Cinzia A., Puglisi, Giovanni
Format: Article
Language:English
Subjects:
Amino Acids - chemistry
Amino Acids - pharmacology
Animals
Biological and medical sciences
Cell Membrane - metabolism
Dose-Response Relationship, Drug
Drug Evaluation, Preclinical - methods
Drug Stability
Fatty Acids - chemistry
Lipids - chemistry
Lipids - pharmacology
Lipoamino acids
Lipophilicity
Liposomes - chemistry
MAO inhibition
Medical sciences
Monoamine Oxidase Inhibitors - chemical synthesis
Monoamine Oxidase Inhibitors - pharmacology
Neuropharmacology
Pharmacology. Drug treatments
Phospholipids - chemistry
Prodrugs
Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease)
Psychology. Psychoanalysis. Psychiatry
Psychopharmacology
Rats
Technology, Pharmaceutical
Tranylcypromine
Tranylcypromine - chemistry
Tranylcypromine - pharmacology
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Summary: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.
ISSN:0223-5234
1768-3254
DOI:10.1016/j.ejmech.2005.05.009