The medicinal chemistry of novel iron Chelators for the treatment of cancer
MetadataShow full item record
Cancer is one of the leading causes of death worldwide and there is an increasing need for novel anti-tumor therapeutics with greater selectivity and potency. A new strategy in the treatment of cancer has focused on targeting an essential cell metabolite, iron (Fe). Iron is vital for cell growth and metabolism, forming a crucial component of the active site of ribonucleotide reductase (RR), the rate-limiting enzyme in DNA synthesis. Cancer cells in particular require large amounts of Fe to proliferate, making them more susceptible to the Fe deficiency caused by Fe chelators. Beginning with primordial siderophores, Fe chelators have since evolved to a new generation of potent and efficient anti-cancer agents. Recently, investigations have led to the generation of novel di-2-pyridylketone thiosemicarbazone (DpT) and 2-benzoylpyridine thiosemicarbazone (BpT) ligands that demonstrate marked and selective anti-tumor activity both in vitro and in vivo against a wide spectrum of tumors. The mechanism of action of these novel ligands includes alterations in the expression of key regulatory molecules as well as the generation of redox active Fe complexes. Interestingly, nonsynthetic Fe chelators including silybin and curcumin, both of which are derived from plants, also have a high potential in the treatment of cancer. This review explores the development of novel Fe chelators for the treatment of cancer and their mechanisms of action. © 2011 Bentham Science Publishers Ltd.
Showing items related by title, author, creator and subject.
Mechanism of the induction of endoplasmic reticulum stress by the anti-cancer agent, di-2-pyridylketone 4,4-dimethyl-3-thiosemicarbazone (Dp44mT): Activation of PERK/eIF2a, IRE1a, ATF6 and calmodulin kinaseMerlot, A.; Shafie, N.; Yu, Yu; Richardson, V.; Jansson, P.; Sahni, S.; Lane, D.; Kovacevic, Z.; Kalinowski, D.; Richardson, D. (2016)The endoplasmic reticulum (ER) plays a major role in the synthesis, maturation and folding of proteins and is a critical calcium (Ca2+) reservoir. Cellular stresses lead to an overwhelming accumulation of misfolded proteins ...
Yu, Yu; Gutierrez, E.; Kovacevic, Z.; Saletta, F.; Obeidy, P.; Rahmanto, Y.; Richardson, D. (2012)The study of iron chelators as anti-tumor agents is still in its infancy. Iron is important for cellular proliferation and this is demonstrated by observations that iron-depletion results in cell cycle arrest and also ...
Bp44mT: An orally active iron chelator of the thiosemicarbazone class with potent anti-tumour efficacyYu, Yu; Rahmanto, Y.; Richardson, D. (2012)Background and Purpose: Our previous studies demonstrated that a thiosemicarbazone iron chelator (di-2-pyridylketone-4,4-dimethyl-3- thiosemicarbazone; Dp44mT) possesses potent and selective anti-cancer activity but led ...