Synthesis and Studies of a New Series of Potential Anti‐Cancer Agents: Thiazole‐Thiosemicarbazone Compounds and Their Pd2+ and Cu2+ Metal Complexes

Abstract

Triapine, which has recently made it to stage II clinical trials as an anticancer agent, and other similar α-(N)-heterocyclic thiosemicarbazone compounds act as ribonucleotide reductase poisons. Copper complexes of these same ligands also inhibit cell replication by an entirely different mechanism, attacking Topoisomerase IIα. The focus of this research is on synthesis and characetrization of three new series of α-(N)-heterocyclic thiosemicarbazone ligands based on thiazole-2-carboxaldehyde, 2-acetylthiazole, and 2-acetyl-4-methylthiazole. To these three substrates, seven different thiosemicarbazides were attached tp form the thiosemicarbazones reported here. These 21 new thiosemicarbazone ligands were then chemically characterized. These mono-anionic tridentate ligands were then reacted with Cu(II) and Pd(II) to make square planar complexes . All of the metal complexes and ligands were tested with Minimum Inhibitory Concentration (MIC) studies using seven different microbes to test their potency. As will be shown, many of the new compounds exhibit profound anti-proliferative activity.