title: Designing green derivatives of β-blocker Metoprolol: a tiered approach for green and sustainable pharmacy and chemistry.
abstract: The presences of micro-pollutants (active pharmaceutical ingredients, APIs) are increasingly seen as a challenge of the sustainable management of water resources worldwide due to ineffective effluent treatment and other measures for their input prevention. Therefore, novel approaches are needed like designing greener pharmaceuticals, i.e. better biodegradability in the environment. This study addresses a tiered approach of implementing green and sustainable chemistry principles for theoretically designing better biodegradable and pharmacologically improved pharmaceuticals. Photodegradation process coupled with LC-MS(n) analysis and in silico tools such as quantitative structure-activity relationships (QSAR) analysis and molecular docking proved to be a very significant approach for the preliminary stages of designing chemical structures that would fit into the "benign by design" concept in the direction of green and sustainable pharmacy. Metoprolol (MTL) was used as an example, which itself is not readily biodegradable under conditions found in sewage treatment and the aquatic environment. The study provides the theoretical design of new derivatives of MTL which might have the same or improved pharmacological activity and are more degradable in the environment than MTL. However, the in silico toxicity prediction by QSAR of those photo-TPs indicated few of them might be possibly mutagenic and require further testing. This novel approach of theoretically designing 'green' pharmaceuticals can be considered as a step forward towards the green and sustainable pharmacy field. However, more knowledge and further experience have to be collected on the full scope, opportunities and limitations of this approach.
authors.affiliation: Sustainable Chemistry and Material Resources, Institute of Sustainable and Environmental Chemistry, Leuphana University Lüneburg, C13, DE-21335 Lüneburg, Germany. Electronic address: rastogi@leuphana.de.
authors.forename: Tushar
authors.initials: T
authors.lastname: Rastogi
authors.affiliation: Sustainable Chemistry and Material Resources, Institute of Sustainable and Environmental Chemistry, Leuphana University Lüneburg, C13, DE-21335 Lüneburg, Germany. Electronic address: cleder@leuphana.de.
authors.forename: Christoph
authors.initials: C
authors.lastname: Leder
authors.affiliation: Sustainable Chemistry and Material Resources, Institute of Sustainable and Environmental Chemistry, Leuphana University Lüneburg, C13, DE-21335 Lüneburg, Germany. Electronic address: Klaus.Kuemmerer@uni.leuphana.de.
authors.forename: Klaus
authors.initials: K
authors.lastname: Kümmerer
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000032:analysis / Q000737:chemistry*; D000818:Animals; D001516:Bees; D001673:Biodegradation, Environmental; D003198:Computer Simulation; D015195:Drug Design; D004785:Environmental Pollutants / Q000032:analysis / Q000737:chemistry*; D055772:Green Chemistry Technology; D008790:Metoprolol / Q000031:analogs & derivatives* / Q000032:analysis; D010782:Photolysis; D021281:Quantitative Structure-Activity Relationship
chemical_list: D000319:Adrenergic beta-Antagonists; D004785:Environmental Pollutants; D008790:Metoprolol
keywords: (Quantitative) Structure–activity relationships (QSAR); Benign by design; Beta adrenergic receptor; Metoprolol; Molecular docking; Photolysis