title: New insights into the biological properties of Crocus sativus L.: chemical modifications, human monoamine oxidases inhibition and molecular modeling studies.
abstract: 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.
authors.affiliation: Dipartimento di Chimica e Tecnologie del Farmaco, Sapienza University of Rome, P.le A. Moro 5, 00185 Rome, Italy.
authors.forename: Celeste
authors.initials: C
authors.lastname: De Monte
authors.affiliation: Dipartimento di Chimica e Tecnologie del Farmaco, Sapienza University of Rome, P.le A. Moro 5, 00185 Rome, Italy. Electronic address: simone.carradori@uniroma1.it.
authors.forename: Simone
authors.initials: S
authors.lastname: Carradori
authors.affiliation: Dipartimento di Chimica e Tecnologie del Farmaco, Sapienza University of Rome, P.le A. Moro 5, 00185 Rome, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Chimenti
authors.affiliation: Dipartimento di Chimica e Tecnologie del Farmaco, Sapienza University of Rome, P.le A. Moro 5, 00185 Rome, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Secci
authors.affiliation: Dipartimento di Chimica e Tecnologie del Farmaco, Sapienza University of Rome, P.le A. Moro 5, 00185 Rome, Italy; Istituto di Metodologie Chimiche, Laboratorio di Risonanza Magnetica "Annalaura Segre", CNR, via Salaria km 29.300, 00015 Monterotondo, Rome, Italy.
authors.forename: Luisa
authors.initials: L
authors.lastname: Mannina
authors.affiliation: Dipartimento di Scienze della Salute, "Magna Graecia" University of Catanzaro, Campus Universitario "S. Venuta", Viale Europa Loc. Germaneto, 88100 Catanzaro, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Alcaro
authors.affiliation: Pharmaceutical Chemistry and Centre of Excellence for Pharmaceutical Sciences, School of Pharmacy, North-West University, Private Bag X6001, Potchefstroom 2520, South Africa.
authors.forename: Anél
authors.initials: A
authors.lastname: Petzer
authors.affiliation: Pharmaceutical Chemistry and Centre of Excellence for Pharmaceutical Sciences, School of Pharmacy, North-West University, Private Bag X6001, Potchefstroom 2520, South Africa.
authors.forename: Clarina I
authors.initials: CI
authors.lastname: N'Da
authors.affiliation: Dipartimento di Scienze della Salute, "Magna Graecia" University of Catanzaro, Campus Universitario "S. Venuta", Viale Europa Loc. Germaneto, 88100 Catanzaro, Italy.
authors.forename: Maria Concetta
authors.initials: MC
authors.lastname: Gidaro
authors.affiliation: Dipartimento di Scienze della Salute, "Magna Graecia" University of Catanzaro, Campus Universitario "S. Venuta", Viale Europa Loc. Germaneto, 88100 Catanzaro, Italy.
authors.forename: Giosuè
authors.initials: G
authors.lastname: Costa
authors.affiliation: Dipartimento di Scienze della Salute, "Magna Graecia" University of Catanzaro, Campus Universitario "S. Venuta", Viale Europa Loc. Germaneto, 88100 Catanzaro, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Alcaro
authors.affiliation: Pharmaceutical Chemistry and Centre of Excellence for Pharmaceutical Sciences, School of Pharmacy, North-West University, Private Bag X6001, Potchefstroom 2520, South Africa. Electronic address: jacques.petzer@nwu.ac.za.
authors.forename: Jacobus P
authors.initials: JP
authors.lastname: Petzer
mesh_terms: D027622:Crocus / Q000737:chemistry*; D018360:Crystallography, X-Ray; D053138:Cyclohexenes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008958:Models, Molecular; D015394:Molecular Structure; D008995:Monoamine Oxidase / Q000378:metabolism*; D008996:Monoamine Oxidase Inhibitors / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D018514:Plant Structures / Q000737:chemistry; D013329:Structure-Activity Relationship; D013729:Terpenes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D053138:Cyclohexenes; D008996:Monoamine Oxidase Inhibitors; D013729:Terpenes; C087963:safranal; D008995:Monoamine Oxidase
keywords: Crocin; Crocus sativus L.; Depression; Neurodegenerative disorders; Safranal; hMAO inhibitors