Synthesis and selective human monoamine oxidase B inhibition of heterocyclic hybrids based on hydrazine and thiazole scaffolds.
A new scaffold of hydrazothiazoles has been designed as monoamine oxidase (MAO) inhibitors combining the hydrazine moiety of iproniazid and the thiazole nucleus of glitazones, a class of peroxisome proliferator-activated receptor (PPAR)γ agonists recently co-crystallized with human MAO-B. The resulting derivatives were synthesized and assayed to evaluate their in vitro activity against both the A and B isoforms of hMAO. All compounds were shown to be selective hMAO-B inhibitors with IC(50)  values in the low micromolar/high nanomolar range. Such results suggest that the hydrazothiazole scaffold could be considered as an interesting pharmacophore for the future design of new lead compounds as coadjuvants for the treatment of neurodegenerative diseases.
Department of Drug Chemistry and Technologies, Sapienza University, Rome, Italy. simone.carradori@uniroma1.it
Simone
S
Carradori
Melissa
M
D'Ascenzio
Celeste
C
De Monte
Daniela
D
Secci
Matilde
M
Yáñez
D000818:Animals; D003460:Crystallization; D015195:Drug Design; D006571:Heterocyclic Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D006834:Hydrazines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D020128:Inhibitory Concentration 50; D007313:Insecta / Q000166:cytology; D008995:Monoamine Oxidase / Q000187:drug effects*; D008996:Monoamine Oxidase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013844:Thiazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
D006571:Heterocyclic Compounds; D006834:Hydrazines; D008996:Monoamine Oxidase Inhibitors; D013844:Thiazoles; D008995:Monoamine Oxidase