Advances in thiosemicarbazone metal complexes as anti-lung cancer agents

Abstract

The great success of cisplatin as a chemotherapeutic agent considerably increased research efforts in inorganic biochemistry to identify more metallic drugs having the potential of treating lung cancer. Metal coordination centres, which exhibit a wide range of coordination numbers and geometries, various oxidised and reduced states and the inherent ligand properties offer pharmaceutical chemists a plethora of drug structures. Owing to the presence of C=N and C=S bonds in a thiosemicarbazone Schiff base, N and S atoms in its hybrid orbital has lone pair of electrons, which can generate metal complexes with different stabilities with most metal elements under certain conditions. Such ligands and complexes play key roles in the treatment of anti-lung cancer. Research regarding metallic anti-lung cancer has advanced considerably, but there remain several challenges. In this review, we discuss the potential of thiosemicarbazone Schiff base complexes as anti-lung cancer drugs, their anti-cancer activities and the most likely action mechanisms involving the recent families of copper, nickel, platinum, ruthenium and other complexes.

5‐Nitrofuryl‐Containing Thiosemicarbazone Gold(I) Compounds: Synthesis, Stability Studies, and Anticancer Activity

“…[28,30,31] TSCs can be functionalized with diverse bioactive or pharmacophoric groups and have been amply studied in medicinal chemistry [31,32] including clinical trials for multiple cancers (NCT02595879, NCT02688101, and NCT02433626). [19,33] Studies have shown that the anti-tumor activity of the thiosemicarbazones is due to their ability to act by multiple mechanisms of action, [34][35][36][37][38][39][40] such as inhibition of DNA synthesis, inhibition of cell proliferation, cell cycle, angiogenesis and metastasis, and modulation of signaling pathways. [39,40] These effects are produced by inhibition of targets such cysteine proteases, [33,37] ribonucleotide reductase, [36] cysteine proteases, [33,37] and/or the generation of reactive oxygen species (ROS).…”

“…[19,33] Studies have shown that the anti-tumor activity of the thiosemicarbazones is due to their ability to act by multiple mechanisms of action, [34][35][36][37][38][39][40] such as inhibition of DNA synthesis, inhibition of cell proliferation, cell cycle, angiogenesis and metastasis, and modulation of signaling pathways. [39,40] These effects are produced by inhibition of targets such cysteine proteases, [33,37] ribonucleotide reductase, [36] cysteine proteases, [33,37] and/or the generation of reactive oxygen species (ROS). [38] Thiosemicarbazones contain a soft sulfur donor atom able to easily coordinate to gold(I) centers.…”

Developing an Anticancer Platinum(II) Compound Based on the Uniqueness of Human Serum Albumin

“…Thiosemicarbazone compounds are not only promising anticancer agents but can also be easily coordinated with metals because they contain sulfur atoms and nitrogen atoms. − To obtain a Pt­(II) thiosemicarbazone compound with remarkable cytotoxicity and low toxicity, we designed and synthesized a series of Pt­(II) thiosemicarbazone compounds. The crystal structures of four Pt­(II) compounds (C1–C4) were identified by X-ray crystallography (Figure ).…”

Perchlorate-induced structural diversity in thiosemicarbazone copper(ii) complexes provides insights to understand the reactivity in acidic and basic media

“…Thiosemicarbazones (TSCs) and their metal complexes have been proposed to exhibit a wide range of biological activities [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15] and tested as drugs against microbial diseases (malaria, [16][17][18] tuberculosis, 19,20 smallpox, 21,22 influenza, 23 leishmaniasis 24,25 ), neurological pathologies (Alzheimer's, [26][27][28][29] Parkinson's 30 ) and cancer. [31][32][33][34][35] Several biochemical targets have been identified, [36][37][38][39][40][41][42][43] while the formation of TSC-Fe and TSC-Cu complexes seems to play an important role in their affectation to cells. [44][45][46][47][48]…”