Psoralen and bergapten: In silico metabolism and toxicophoric analysis of drugs used to treat vitiligo

Abstract

Purpose. To discuss the contribution of psoralen and bergapten metabolites on psoralens toxicity. Methods. Computational chemistry prediction of metabolic reactions and toxicophoric groups based on the expert systems Derek and Meteor. Results. A total of 15 metabolites were suggested for both psoralen and bergapten based on phase 1 and 2 biotransformations until the 3rd generation. Five toxicophoric substructures were shared among psoralen, bergapten and their corresponding metabolites; one toxicophoric marker (resorcinol) was only identified in bergapten and its biotransformation products. Conclusion. Although the toxic effects of psoralens are well known and documented, there is little information concerning the role of their metabolites in this process. We believe this work adds to the knowledge of which molecular substructures are relevant to the process of metabolism and toxicity induction, thus, guiding the search and development of more effective and less toxic drugs to treat vitiligo.