Thieno[2,3‐<i>b</i>]pyridine amines: Synthesis and evaluation of tacrine analogs against biological activities related to Alzheimer's disease
Mina Saeedi, Maliheh Safavi, Emad Allahabadi, Arezoo Rastegari, Roshanak Hariri, Sanaz Jafari, Syed Nasir Abbas Bukhari, Seyedeh Sara Mirfazli, Omidreza Firuzi, Najmeh Edraki, Mohammad Mahdavi, Tahmineh Akbarzadeh
Abstract
Abstract In search of safer tacrine analogs, various thieno[2,3‐ b ]pyridine amine derivatives were synthesized and evaluated for their inhibitory activity against cholinesterases (ChEs). Among the synthesized compounds, compounds 5e and 5d showed the highest activity towards acetylcholinesterase and butyrylcholinesterase, with IC 50 values of 1.55 and 0.23 µM, respectively. The most active ChE inhibitors ( 5e and 5d ) were also candidates for further complementary assays, such as kinetic and molecular docking studies as well as studies on inhibitory activity towards amyloid‐beta (βA) aggregation and β‐secretase 1, neuroprotectivity, and cytotoxicity against HepG2 cells. Our results indicated efficient anti‐Alzheimer's activity of the synthesized compounds.