Cytotoxicity and structure–activity relationships of four α-N-heterocyclic thiosemicarbazone derivatives crystal structure of 2-acetylpyrazine thiosemicarbazone

Abstract

A series of thiosemicarbazone ligands, HL 1 (2-acetylpyrazine thiosemicarbazone), HL 2 (2-acetylpyrazine N(4)-methylthiosemicarbazone), HL 3 (2-benzoylpyridine thiosemicarbazone) and HL 4 (2-benzoylpyridine N(4)-methylthiosemicarbazone), have been synthesized. The crystal structure of HL 1 has been determined by single-crystal X-ray diffraction. Hydrogen bonds link the different components to stabilize the crystal structure. The antitumor activity of the four ligands were tested against K562 leucocythemia and BEL7402 liver cancer cell lines. All the thiosemicarbazones showed significant antitumor activity. Different substituents on the ligands show different levels of antitumor activity. By comparison with the other thiosemicarbazone species studied, HL 4 with substitution at N(4) position in thiosemicarbazone along with 2-benzoylpyridine is the most active thiosemicarbazone ligand with IC 50 = 0.002 μm in the K562 leucocythemia cell line and 0.138 μm in the BEL7402 liver cancer cell line, respectively.