New insights into the biological properties of Crocus sativus L.: chemical modifications, human monoamine oxidases inhibition and molecular modeling studies

• Active principles of Crocus sativus L. were investigated for their hMAO inhibition.
• We obtained semisynthetic derivatives from safranal with different isoform selectivity.
• Biological data confirmed the molecular bases of pharmacological applications of Saffron.
• Molecular modeling studies suggested a non-competitive inhibitory mechanism for crocin.

Although there are clinical trials and in vivo studies in literature regarding the anxiolytic and antidepressant activities of the components of Crocus sativus L., their effects on the human monoamine oxidases (hMAO-A and hMAO-B), enzymes which are involved in mental disorders and neurodegenerative diseases, have not yet been investigated. We have thus examined the hMAO inhibitory activities of crocin and safranal (the most important active principles in saffron) and, subsequently, designed a series of safranal derivatives to evaluate which chemical modifications confer enhanced inhibition of the hMAO isoforms. Docking simulations were performed in order to identify key molecular recognitions of these inhibitors with both isoforms of hMAO. In this regard, different mechanisms of action were revealed. This study concludes that safranal and crocin represent useful leads for the discovery of novel hMAO inhibitors for the clinical management of psychiatric and neurodegenerative disorders.

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