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Synthesis and Studies of a New Series of Potential Anti‐Cancer Agents: Thiazole‐Thiosemicarbazone Compounds and Their Pd 2+ and Cu 2+ Metal Complexes
Author(s) -
Rand Victoria,
Conner Jennifer,
Simpson Shawna,
Koch Amanda,
Lisic Edward
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.897.24
Subject(s) - semicarbazone , ribonucleotide reductase , thiazole , chemistry , stereochemistry , metal , gold compounds , combinatorial chemistry , medicinal chemistry , biochemistry , organic chemistry , protein subunit , gene
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.