Purpose: To synthesize novel tris-diamine-derived transition metal complexes of flurbiprofen M(C2H8N2)3 (fp)2 and M(C3H10N2)3 (fp)2, and to evaluate their acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activities.Method: Tris-diamine-derived transition metal complexes of Co(II), Ni(II), and Mn(II) were synthesized and characterized using ultraviolet-visible (UV-Vis) spectroscopy, Fourier transform-infrared (FT-IR) spectroscopy, elemental analysis, magnetic susceptibility, conductivity measurement and single crystal x-ray analysis. The synthesized complexes were also evaluated for their AChE and BChE inhibitory activities.Results: Based on magnetic susceptibility and electronic studies, the synthesized complexes possessed distorted octahedral geometry. Conductance measurements indicated that diamine-derived metal complexes of flurbiprofen were electrolytes, whereas, simple metal complexes of flurbiprofen were non-electrolytes. The structure of Ni (C2H8N2)3 (fp)2 was also confirmed by single crystal x-ray analysis. The synthesized metal complexes exhibited moderate-to-very good inhibition of AChE and BChE. In vitro assays revealed that Ni complexes were most active, with the least half-maximal inhibitory concentration (IC50) values against AChE and BChE, compared to Co and Mn complexes. Furthermore, 1, 2-diaminoethane-derived complexes were more potent, with lower IC50 values against both AChE and BChE, compared to 1,3-diaminopropane-derived complexes. Among the complexes, 4a and 5a revealed significant cholinesterase inhibitory activities relative to the standard drug, galantamine.Conclusion: All the synthesized metal complexes are active against AChE and BChE, but only 4a and 5a are more active than the standard drug, galantamine, indicating their potential for drug development.Keywords: Flurbiprofen, Cholinesterase, Diamines, Galantamine, Metal complexes, Cholinesterase inhibitio
