title: Enhancement of drug affinity for cell membranes by conjugation with lipoamino acids. I. Synthesis and biological evaluation of lipophilic conjugates of tranylcypromine.
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.
authors.affiliation: Dipartimento di Scienze Farmaceutiche, Università degli Studi di Catania, Viale A. Doria, 6, I-95125 Catania, Italy. r.pignatello@unict.it
authors.forename: Rosario
authors.initials: R
authors.lastname: Pignatello
authors.forename: Antonina
authors.initials: A
authors.lastname: Puleo
authors.forename: Salvatore
authors.initials: S
authors.lastname: Guccione
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Raciti
authors.forename: Rosaria
authors.initials: R
authors.lastname: Acquaviva
authors.forename: Agatina
authors.initials: A
authors.lastname: Campisi
authors.forename: Cinzia A
authors.initials: CA
authors.lastname: Ventura
authors.forename: Giovanni
authors.initials: G
authors.lastname: Puglisi
mesh_terms: 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
chemical_list: D000596:Amino Acids; D005227:Fatty Acids; D008055:Lipids; D008081:Liposomes; D008996:Monoamine Oxidase Inhibitors; D010743:Phospholipids; D014191:Tranylcypromine