New Highly Efficient Multifunctional Cholinesterase Inhibitors Based on the Conjugation of Amiridine and Tacrine Homolog

The synthesis of new hybrid compounds based on the domestic drug amiridine and a seven-membered cyclic homolog of tacrine combined by a thiourea-containing spacer was described. The synthesized conjugates were shown to be highly efficient inhibitors of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) with a nanomolar activity exceeding that of amyridine and tacrine, which was consistent with the molecular docking results. The conjugates also demonstrated a broader spectrum of biological activity uncharacteristic of the parent pharmacophores, namely, the ability to inhibit the AChE-induced and self-aggregation of β-amyloid and antioxidant properties.