Synthesis, structure, antiproliferative activity and molecular docking of divalent and trivalent metal complexes of 4H-3,5-diamino-1,2,4-triazole and α-hydroxynaphthaldehyde Schiff base ligand

Cu(II), Co(II), Mn(II), Cr(III) and Mn(III) chelates of the ligand obtained by the condensation of 4H-3,5-diamino-1,2,4-triazole and 2-hydroxy-1-naphthaldehyde have been isolated and characterized by means of elemental analysis, inductively coupled plasma analysis, mass spectrometry, Fourier transform infrared and UV-visible spectroscopies, magnetic measurements and thermal analysis. The analytical results indicated the formation of the metal complexes in a ligand-to-metal molar ratio of 1:2. The ligand is connected to the metal ion in a tetradentate fashion coordinating to the metal center through the azomethine nitrogens and deprotonated phenolic OH groups. The spectral and magnetic results supported the formation of octahedral geometry around the Cu(II), Mn(III) and Cr(III) centers while Co(II) and Mn(II) centers were confirmed to have tetrahedral geometry. Molecular docking was used to predict the binding between the ligand and the oncogenic protein H-ras (121p). The antiproliferative activity of the compounds under study was evaluated in vitro using MTT assay against liver carcinoma (HepG2) and breast cancer (MCF-7) cell lines comparing with cisplatin. The binding mode of selected metal chelates with salmon serum DNA was investigated using the electronic absorption titration method.