Abstract
Thiosemicarbazones (TSCs) are a class of Schiff bases usually obtained by the condensation of thiosemicarbazide with a suitable aldehyde or ketone. TSCs have been the focus of chemists and biologists due to their wide range of pharmacological effects. One of the promising areas in which these excellent metal chelators are being developed is their use against cancer. TSCs have a wide clinical antitumor spectrum with efficacy in various tumor types such as leukemia, pancreatic cancer, breast cancer, non-small cell lung cancer, cervical cancer, prostate cancer and bladder cancer. To obtain better activity, different series of TSCs have been developed by modifying the heteroaromatic system in their molecules. These compounds possessed significant antineoplastic activity when the carbonyl attachment of the side chain was located at a position α to the ring nitrogen atom, whereas attachment of the side chain β or γ to the heterocyclic N atom resulted in inactive antitumor agents. In addition, replacement of the heterocyclic ring N with C also resulted in a biologically inactive compound suggesting that a conjugated N,N,S-tridentate donor set is essential for the biological activities of thiosemicarbazones. Several possible mechanisms have been implemented for the anticancer activity of thiosemicarbazones.
Keywords: Cancer, thiosemicarbazone, iron chelation, ribonucleotide reductase, reactive oxygen species, apoptosis.
Graphical Abstract
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