Synthesis, characterization, antitumor activity, molecular modeling and docking of new ligand, (2,5-pyrrole)-bis(5,6-diphenyl-[1,2,4]-triazin-3-yl)hydrazone and its complexes

Abstract

Reactions of (2,5-pyrrole)-bis(5,6-diphenyl-[1,2,4]-triazin-3-ylhydrazone) ligand, (H2L; H2BisT) with VO(II), Co(II), Ni(II) and several copper(II) salts, including NO3−, AcO−, Cl− and SO42−, in presence of LiOH (in molar ratio 1:2:2, ligand:LiOH:metal) afforded mono- and bi-nuclear metal complexes. Characterization of H2BisT and its metal complexes was achieved by elemental analyses, conductance, magnetic moments, TG measurements, electronic, infrared and ESR spectral data. H2BisT acts as a neutral or dibasic tetradentate ligand, coordinating via two N-azomethine and two N-triazine atoms for all metal complexes. The morphological structure of H2BisT is determined using SEM, which changed by complexation to agglomerated spherical and sheet like shapes. The metal complexes have square pyramidal, square planar in addition to octahedral geometry. The theoretical parameters of H2BisT and its metal complexes have been calculated by Hyperchem program, PM3 method. Also, the best relations found from experimental (IR & UV–Vis spectra) and theoretical data. H2BisT and some complexes showed antitumor activity toward Hepatocellular carcinoma cells (Hep G-2). The molecular docking studies for H2BisT, chloro and acetato Cu(II) complexes were performed using MOE 2014.0901 software (PDB. I.D.3ce3). The docking data agreed with the antitumor activity results, where acetato Cu(II) complex had higher activity due to forming 5 H-bonds, while chloro Cu(II) complex had moderated activity as it could form only two hydrogen bonds. On the other hand, H2BisT had low activity with only Pi-cation bond formation.