Synthesis, characterization, and in vitro anti-neoplastic activity of novel vic-dioximes bearing thiosemicarbazone side groups and their mononuclear complexes

Abstract

Two novel vicinal dioxime ligands containing thiosemicarbazone units, (2E)-2-[4-(diethylamino)benzylidene]-N-[(1Z,2E)-N-hydroxy-2-(hydroxyimino)ethanimidoyl]hydrazine carbothioamide (L(1)H2) and (2E)-2-[4-(dimethylamino)benzylidene]-N-[(1Z,2E)-N-hydroxy-2-(hydroxyimino)ethanimidoyl]hydrazinecarbothioamide (L(2)H2), were synthesized. Using the HL-60 human leukemia cell line, the in vitro anti-neoplastic activity of these thiosemicarbazone-oxime derivatives was evaluated. Mononuclear nickel(II), copper(II), and cobalt(II) complexes with a metal:ligand ratio of 1:2 for both the L(1)H2 and L(2)H2 ligands were also synthesized. To characterize these compounds, Fourier transform-infrared spectroscopy (FT-IR), mass spectrometry (MS), magnetic susceptibility measurements, (1)H and (13)C nuclear magnetic resonance (NMR), ultraviolet-visible (UV-Vis) absorption spectroscopy, heteronuclear multiple-bond correlation (HMQC), and elemental analysis were performed. For L(1)H2, L(2)H2, and each of their derivatives, antiproliferative effects against HL-60 cells were exhibited and the associated IpC50 values ranged from 5μM to 20μM. Furthermore, L(1)H2 and its derivatives inhibited the proliferation of HL-60 cells more effectively than L(2)H2, and 5μM [Cu(L(1)H)2] exhibited the strongest antiproliferative activity.

Keywords: Antiproliferative; Hydrogen-bridge complex; Leukemia; Thiosemicarbazone; Transition metal complex; Vic-dioxime.