Abstract:
: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 apoptosis. In addition, many iron chelators are known to inhibit ribonucleotide reductase, the iron-containing enzyme that is the rate-limiting step for DNA synthesis. Desferrioxamine is a well known chelator used for the treatment of iron-overload disease, but it has also been shown to possess anti-cancer activity. Another class of chelators, namely the thiosemicarbazones, have been shown to possess anti-cancer activity since the 1950's, although their mechanism(s) of action have only recently been more comprehensively elucidated. In fact, the redox activity of thiosemicarbazone iron complexes is thought to be important in mediating their potent cytotoxicity. Moreover, unlike typical iron chelators which simply act to deplete tumors of iron, several thiosemicarbazones (i.e., Bp44mT and Dp44mT) do not induce this effect, their anti-cancer efficacy being due to other mechanisms e.g., redox activity. Other reports have also shown that some thiosemicarbazones inhibit topoisomerase IIα, demonstrating that this class of agents have multiple molecular targets and act by various mechanisms. The most well characterized thiosemicarbazone iron chelator in terms of its assessment in humans is 3-aminopyridine-2-carboxaldehyde thiosemicarbazone (3-AP). Observations from these clinical trials highlight the less than optimal activity of this ligand and several side effects related to its use, including myelo-suppression, hypoxia and methemoglobinemia. The mechanisms responsible for these latter effects must be elucidated and the design of the ligand altered to minimize these problems and increase efficacy. This review discusses the development of chelators as unique agents for cancer treatment.
journal_name
Curr Med Chemjournal_title
Current medicinal chemistryauthors
Yu Y,Gutierrez E,Kovacevic Z,Saletta F,Obeidy P,Suryo Rahmanto Y,Richardson DRdoi
10.2174/092986712800609706subject
Has Abstractpub_date
2012-01-01 00:00:00pages
2689-702issue
17eissn
0929-8673issn
1875-533Xpii
CMC-EPUB-20120326-002journal_volume
19pub_type
杂志文章,评审abstract::N-BP, rapamycin and its derivatives have been originally developed respectively as anti-resorptive and anti-fungal agents. In fact, in vitro and in vivo experiments demonstrated that these compounds are multi-functional molecules exerting their effects on tumour cell growth and bone remodelling. The major challenge in...
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更新日期:2011-01-01 00:00:00
abstract::The chemokine receptor, CXCR4, is a GPCR that transduces signals of its endogenous ligand, CXCL12 (stromal cell-derived factor-1, SDF-1). The CXCL12-CXCR4 system plays an important role in the migration of progenitors during embryologic development of the cardiovascular, hemopoietic, central nervous systems, etc. This...
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更新日期:2007-01-01 00:00:00
abstract:BACKGROUND:Glioma is a heterogeneous, highly complicated central nervous system (CNS) tumor with uncertain mechanism of initiation and progression, resulting in an unfavorable outcome. An extended network of cytokines is recognized as a major regulator of glioma pathogenesis, either promoting or inhibiting glioma progr...
journal_title:Current medicinal chemistry
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更新日期:2018-01-01 00:00:00
abstract::The stilbene scaffold is a basic element for a number of biologically active natural and synthetic compounds, and it is considered as a privileged structure. Stilbenes exemplified by resveratrol, combretastatin A-4 and pterostilbene are of significant interest for drug research and development because of their potenti...
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更新日期:2016-01-01 00:00:00
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更新日期:2008-01-01 00:00:00
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更新日期:2015-01-01 00:00:00
abstract::Nitric Oxide (NO) is a signaling radical, highly diffusible pleiotropic regulator of a large set of different molecular and biological pathways, including, neurotransmission, vasodilatation and macrophagemediated responses against infections. It is produced from the amino acid L-Arginine and oxygen by the enzymatic ac...
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更新日期:2016-01-01 00:00:00
abstract::Thermosensitive hydrogels are very important biomaterials used in drug delivery systems (DDSs), which gained increasing attention of researchers. Thermosensitive hydrogels have great potential in various applications, such as drug delivery, cell encapsulation, tissue engineering, and etc. Especially, injectable thermo...
journal_title:Current medicinal chemistry
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更新日期:2013-01-01 00:00:00
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更新日期:2011-01-01 00:00:00
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abstract:BACKGROUND:In the last two decades, there have been significant technological advances in the early detection of brain tumors. However, no notable improvements have been observed in the treatment of Glioblastoma Multiforme (GBM), the most common brain neoplasm coupled with the worst prognosis. GBM is characterized by a...
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更新日期:2017-01-01 00:00:00
abstract::The synthesis of oxacephalotin and oxacephamandol, which are more active than natural, sulfur-containing congeners, and the isolation of clavulanic acid, a potent inhibitor of beta-lactamase enzymes, directed attention of many academic and industrial laboratories the synthesis of oxygen analogues of penicillins and ce...
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abstract::Phosphonated nucleosides represent a promising alternative in the improvement of the biological activity of nucleoside analogues in antiviral and anticancer chemotherapy. The basic concept, the chemistry, the different structural modifications and their effects on the antiviral potency will be discussed in this review...
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abstract:BACKGROUND:Steroid hormones belong to a group of low-molecular weight compounds which are responsible for maintenance of various body functions, thus, their accurate assessment is crucial for evaluation of biosynthetic defects. The development of reliable methods allowing disease diagnosis is essential to improve early...
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更新日期:2019-01-01 00:00:00
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更新日期:2006-01-01 00:00:00