: It has long been established that mitochondrial dysfunction in Alzheimer's disease (AD) patients can trigger pathological changes in cell metabolism by altering metabolic enzymes such as the mitochondrial 17β-hydroxysteroid dehydrogenase type 10 (17β-HSD10), also known as amyloid-binding alcohol dehydrogenase (ABAD). We and others have shown that frentizole and riluzole derivatives can inhibit 17β-HSD10 and that this inhibition is beneficial and holds therapeutic merit for the treatment of AD. Here we evaluate several novel series based on benzothiazolylurea scaffold evaluating key structural and activity relationships required for the inhibition of 17β-HSD10. Results show that the most promising of these compounds have markedly increased potency on our previously published inhibitors, with the most promising exhibiting advantageous features like low cytotoxicity and target engagement in living cells.

• MeSH
• 17-hydroxysteroidní dehydrogenasy antagonisté a inhibitory   chemie   MeSH
• Alzheimerova nemoc farmakoterapie   MeSH
• amyloidní beta-protein metabolismus   MeSH
• benzothiazoly chemie   MeSH
• buněčné linie MeSH
• lidé MeSH
• mitochondrie metabolismus   MeSH
• močovina chemie   MeSH
• molekulární struktura MeSH
• racionální návrh léčiv MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• vztahy mezi strukturou a aktivitou MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH