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 alsoprovide the conjugated drugs a ‘membrane-like character’, capable to facilitate their interaction with and penetration through cell membranesand biological barriers. To study such a feature, our aim is to collect experimental and computational data using a novel series of lipophilicconjugates between a model drug (tranylcypromine (TCP)) and LAA residues containing a short, a medium or a long alkyl side chain (C-4 toC-16), to provide a wide range of lipophilicity. For comparison, a corresponding set of amides of TCP with alkanoic or fatty acids wasprepared and characterized. Their in vitro monoamine oxidase inhibitory activity also tested.