Identification of multi-target compounds against Alzheimer's disease

Alzheimer's Disease (AD) is a neurological disorder that leads to memory weakening, loss of language, death and there is no cure⁠. In this context, the present study prioritized multi-target compounds that can act against three receptors: acetylcholinesterase (AchE/4EY7), butyrilcholinesterase (BChe/4TPK) and beta-secretase-1 (BACE-1/4D8C) for the AD treatmen. Additionally, we used ligand and structure based virtual screening methods by ZINCPharm, Autodock Vina1.1.2 and Dock6 to identify potential compounds able to inhibity these targets. From a library of 20 million molecules led us to identify nine compounds that presented better interaction energy values than redocking, around -10.0 to -11.0 (redocking = -8.4); -10.8 to -11.5 (redocking = -10.7); and -9.9 to -11.5 (redocking = -9.7), in Kcal.mol-1, for AChE, BChe and BACE-1, respectively. The compounds interacted with Tyr73, Ser293, Ser298 and Tyr344 to 4EY7; Gly175, Thr179, Pro344 and Ser346 to 4TPK; Gly53, Gly76,Glu263 and Thr265 to 4D8C.These findings corroborated with previous reports.