Tris-diamine-derived transition metal complexes of flurbiprofen as cholinesterase inhibitors

  • Muhammad Jamil
  • Nargis Sultana
  • Rizwan Ashraf
  • Muhammad Sarfraz
  • Muhammad Ilyas Tariq
  • Muhammad Mustaqeem
Keywords: Flurbiprofen, Cholinesterase, Diamines, Galantamine, Metal complexes, Cholinesterase inhibition

Abstract

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 inhibition

Published
2018-05-09
Section
Articles

Journal Identifiers


eISSN: 1596-9827
print ISSN: 1596-5996