Synthesis, characterization and biological activity of Mn(II), Co(II), Ni(II), Cu(II) and Zn(II) complexes derived from Schiff base ligand quinoxaline-2-carboxaldehyde and 4-aminoantipyrine

Abstract

A series of novel metal complexes of 4-aminoantipyrine quinoxaline (4-AAPQ) Schiff base derived from 4-aminoantipyrine and quinoxaline-2-carboxaldehyde were synthesized. The structural and properties of these compounds were characterized by spectral methods (IR, mass, ¹H NMR, ¹³C NMR, UV–Vis), molar conductance, and elemental analysis. The binding stoichiometry mode was confirmed as 1:1 (metal: ligand) by analytical, and spectral data. The type of coordination of the metal to azomethine nitrogen and quinoxaline nitrogen atoms of the ligand were determined by spectral data. In this case, the ligand acts as a bidentate donor with the coordination number of four in prepared complexes. The synthesized compounds were tested for two types of cancer cell lines consisting of human colon cancer (HT-29) and breast cancer (MCF-7), as well as one normal cell line containing human foreskin fibroblast (HFF) using MTT cell viability assay. A comparative study of the IC₅₀ values indicates that 4-AAPQ-Cu (II)/ and Mn(II) complexes exhibit higher activity than related Schiff base ligand on the MCF-7 cell line. Also, 4-AAPQ-Mn(II)/ and -Zn(II) complexes were the most active compounds with the highest inhibition against HT-29 cell line after 48 h. Molecular docking studies of 4-AAPQ Cu(II) within the c-kit active site as a validated target displayed 344.33 nM and -8.82 kcal/mol for inhibition constant (Ki) and free energy of binding, respectively.