4-(3-Nitrophenyl)thiazol-2-ylhydrazone derivatives as antioxidants and selective hMAO-B inhibitors: synthesis, biological activity and computational analysis

• Main Authors: Daniela Secci, Simone Carradori, Anél Petzer, Paolo Guglielmi, Melissa D’Ascenzio, Paola Chimenti, Donatella Bagetta, Stefano Alcaro, Gokhan Zengin, Jacobus P. Petzer, Francesco Ortuso
• Format: Article
• Language: English
• Published: Taylor & Francis Group 2019-01-01
• Series: Journal of Enzyme Inhibition and Medicinal Chemistry
• Subjects: (thiazol-2-yl)hydrazone derivatives; alzheimer’s disease; parkinson’s disease; selective; monoamine oxidase; inhibitor; antioxidants; molecular modelling
• Online Access: http://dx.doi.org/10.1080/14756366.2019.1571272

A new series of 4-(3-nitrophenyl)thiazol-2-ylhydrazone derivatives were designed, synthesised, and evaluated to assess their inhibitory effect on the human monoamine oxidase (hMAO) A and B isoforms. Different (un)substituted (hetero)aromatic substituents were linked to N1 of the hydrazone in order to establish robust structure–activity relationships. The results of the biological testing demonstrated that the presence of the hydrazothiazole nucleus bearing at C4 a phenyl ring functionalised at the meta position with a nitro group represents an important pharmacophoric feature to obtain selective and reversible human MAO-B inhibition for the treatment of neurodegenerative disorders. In addition, the most potent and selective MAO-B inhibitors were evaluated in silico as potential cholinesterase (AChE/BuChE) inhibitors and in vitro for antioxidant activities. The results obtained from molecular modelling studies provided insight into the multiple interactions and structural requirements for the reported MAO inhibitory properties.