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. 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.
Pignatello
Rosario
R
Dipartimento di Scienze Farmaceutiche, Università degli Studi di Catania, Viale A. Doria, 6, I-95125 Catania, Italy. r.pignatello@unict.it
Puleo
Antonina
A
Guccione
Salvatore
S
Raciti
Giuseppina
G
Acquaviva
Rosaria
R
Campisi
Agatina
A
Ventura
Cinzia A
CA
Puglisi
Giovanni
G
D000596:Amino Acids / Q000737:chemistry* / Q000494:pharmacology; D000818:Animals; D002462:Cell Membrane / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical / Q000379:methods; D004355:Drug Stability; D005227:Fatty Acids / Q000737:chemistry; D008055:Lipids / Q000737:chemistry* / Q000494:pharmacology; D008081:Liposomes / Q000737:chemistry; D008996:Monoamine Oxidase Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology; D010743:Phospholipids / Q000737:chemistry; D051381:Rats; D013678:Technology, Pharmaceutical; D014191:Tranylcypromine / Q000737:chemistry* / Q000494:pharmacology
D000596:Amino Acids; D005227:Fatty Acids; D008055:Lipids; D008081:Liposomes; D008996:Monoamine Oxidase Inhibitors; D010743:Phospholipids; D014191:Tranylcypromine