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

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• 作者：Rosario Pignatello ; Antonina Puleo ; Salvatore Guccione ; Giuseppina Raciti ; Rosaria Acquaviva ; Agatina Campisi ; Cinzia A. Ventura ; Giovanni Puglisi
• 关键词：Lipoamino acids ; Tranylcypromine ; MAO inhibition ; Lipophilicity ; Prodrugs
• 刊名：European Journal of Medicinal Chemistry
• 出版年：2005
• 出版时间：November 2005
• 年：2005
• 卷：40
• 期：11
• 页码：1074-1079
• 全文大小：202 K

文摘

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.