Synthesis and biological evaluation of some tacrine analogs: study of the effect of the chloro substituent on the acetylcholinesterase inhibitory activity

New tetrahydroquinoline derivatives were synthesized, characterized, and evaluated for their in vitro and in vivo acetylcholinesterase inhibitory activity as well as hepatotoxicity using tacrine as a reference standard. The obtained results revealed that most of the compounds comprising a chloro substituent displayed higher activity when compared with the other analogs. Among the newly synthesized compounds, four analogs displayed in vitro and in vivo acetylcholinesterase inhibitory activity comparable to or slightly higher than tacrine. Among these compounds, the 2-chlorotetrahydroquinoline derivative emerged with hepatotoxicity results comparable to saline.