Low toxicity ferrocene-1,2,3-Triazole hybrids as acetylcholinesterase and butyrylcholinesterase inhibitors: Synthesis, antioxidant activity, enzyme inhibition, cytotoxicity properties and molecular docking studies.

Ferrocene-1,2,3-triazole hybrids have emerged as a new class of compounds with significant potential as anticholinesterase agents. These hybrids uniquely combine the biological properties of ferrocene and the 1,2,3-triazole moiety, both of which are known for their stability and versatile interactions with biomolecules. In this study, the synthesis of various ferrocene-1,2,3-triazole derivatives (9-15) was carried out. All synthesized compounds were characterized using standard techniques. The crystal structures of compounds 10, 13, and 14 were elucidated. Their inhibitory effects on acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes were evaluated. The compounds exhibited an AChE inhibitory effect with an IC50 range of 1.82 to 7.85 μM. Compound 15, containing an aldehyde group at the para position and a hydroxyl group at one of the ortho positions of the phenyl ring, was the most active dual inhibitor among the compounds (IC50 = 1.82 μM for AChE and 0.69 μM for BChE). Furthermore, the in vitro cytotoxic properties of these compounds were investigated against malignant mesothelioma (H2452) cells. Compounds 9-11 exhibited cytotoxicity at 25 μg/mL, whereas compounds 12-15 showed no cytotoxic effects even at 500 μg/mL. The antioxidant activities of all compounds were analyzed using DPPH, ABTS, and CUPRAC methods. All compounds showed higher antioxidant activity than ascorbic acid, Trolox, and BHT.