6-Benzothiazolyl Ureas, Thioureas and Guanidines are Potent Inhibitors of ABAD/17β-HSD10 and Potential Drugs for Alzheimer"s Disease Treatment: Design, Synthesis and in vitro Evaluation

Background: The mitochondrial enzyme amyloid beta-binding alcohol dehydrogenase (ABAD) also known as 17β-hydroxysteroid dehydrogenase type 10 (17β-HSD10) has been connected with the pathogenesis of Alzheimer’s disease (AD). ABAD/17β-HSD10 is a binding site for the amyloid-beta peptide (Aβ) inside the mitochondrial matrix where it exacerbates Aβtoxicity. Interaction between these two proteins triggers a series of events leading to mitochondrial dysfunction as seen in AD. Keywords: 17β-hydroxysteroid dehydrogenase type 10 (17β-HSD10), alzheimer’s disease, amyloid-beta binding alcohol dehydrogenase (ABAD), chemical synthesis, enzyme inhibition, frentizole, pharmacophore modelling, QSAR.