Synthesis of new 1,3,4-thiadiazole derivatives, investigation of their AChE effects

Alzheimer’s disease (AD) is the most common cause of dementia and one of the most prevalent neurodegenerative diseases. It begins with mild cognitive impairment and progressively affects all aspects of the patient’s life functions. Alzheimer’s disease is more commonly seen in the elderly and has a progressive incidence. With the global increase in the elderly population, Alzheimer’s disease poses a significant threat. Additionally, current medications do not prevent AD, highlighting the need for new drug molecules to be used in AD treatment. Although 1,3,4-thiadiazoles have many biological activities such as anticancer and antiviral, their activities on acetylcholinesterase (AChE) are also being investigated. For this purpose, three new 1,3,4-thiadiazole compounds were synthesized in this study. The structure determinations of these compounds were carried out using 1H-NMR and HRMS spectrophotometric methods. Activity studies were conducted in vitro using the modified Ellman method. As a result of the activity tests, compound 3b showed the closest effect to donepezil with an IC50= 0.096±0.004 µM.