Synthesis of new 3-aryl-4,5-dihydropyrazole-1-carbothioamide derivatives. An investigation on their ability to inhibit monoamine oxidase

• Published in: European journal of medicinal chemistry 2010-10, Vol.45 (10), p.4490-4498
• Main Authors: Maccioni, E., Alcaro, S., Orallo, F., Cardia, M.C., Distinto, S., Costa, G., Yanez, M., Sanna, M.L., Vigo, S., Meleddu, R., Secci, D.
• Format: Article
• Language: English
• Subjects: Animals; Anticonvulsants. Antiepileptics. Antiparkinson agents; Biological and medical sciences; Cell Line; Dihydropyrazole synthesis and characterization; Docking; Humans; Insecta; Medical sciences; Models, Molecular; Monoamine Oxidase - metabolism; Monoamine Oxidase Inhibitors - chemical synthesis; Monoamine Oxidase Inhibitors - chemistry; Monoamine Oxidase Inhibitors - pharmacology; Monoamine oxidase selective inhibition; Neuropharmacology; Parkinson disease; Pharmacology. Drug treatments; Protein Binding; Pyrazoles - chemical synthesis; Pyrazoles - chemistry; Pyrazoles - pharmacology; Recombinant Proteins - antagonists & inhibitors; Recombinant Proteins - metabolism; Structure-Activity Relationship; Thioamides - chemical synthesis; Thioamides - chemistry; Thioamides - pharmacology
• ISSN: 0223-5234; 1768-3254
• DOI: 10.1016/j.ejmech.2010.07.009

Some differently substituted 3-aryl-4,5-dihydropyrazoles-1-carbothioamides have been synthesised with the aim to investigate their monoamine oxidase inhibitory activity. The chemical structures of the compounds have been characterized by means of their IR, 1H NMR, 13C NMR spectroscopic data and elemental analyses. All the active compounds showed a selective activity towards the B isoform of the enzyme, regardless of the substitution on the heterocyclic ring. The inhibition of the enzymatic activity was measured on human recombinant MAO isoforms, expressed in baculovirus infected BTI insect cells. Docking experiments were carried out with the aim to rationalize the mechanism of inhibition of the most active and selective compound. All the active compounds showed a selective activity towards the B isoform of the enzyme, regardless of the substitution on the heterocyclic ring. 3-(4-methoxyphenyl) substituted pyrazolines were the most active within the tested compounds. [Display omitted]