A further indepth analysis on the therapeutic potential of gold complexes as anticancer drugs has recently been published. Cancer treatment using gold in treatment of cancer. A new era of metalbased drugs started in the 1960s, heralded by the discovery of. The area of gold complexes with anticancer activity has developed fast. New trends for metal complexes with anticancer activity. Current progresses in metalbased anticancer complexes as.
This thesis focuses on the development of gold and nonclassical platinumbased anticancer agents that display distinctively different anticancer mechanisms compared to the commonly used cisplatin. Gold complexes and their anticancer properties springerlink. The design of an effective anticancer agent is a complicated game that must encompass not only the drugs inherent inhibitory properties but also its delivery, dosage, and residence time in vivo. Currently, metallodrugs with anticancer activity, especially gold and platinum complexes, have an enormous impact on clinical cancer chemotherapy. Significant side effects and drug resistance, however, have limited its clinical applications. This perspective covers the recent contributions of the che laboratory to the development of transitionmetalbased anticancer complexes, including gold, platinum, ruthenium and iron complexes. Metal properties offer a wide range of coordination numbers. Department of chemistry, college of science, taibah university, almedina almunawara 41477, department of chemistry, jamia millia islamia. Goldiii compounds as new family of anticancer drugs. Joe gerald jesu raj, devendra deo pathak, pramesh n. Gold complexes as prospective metalbased anticancer drugs.
Medicinal chemistry of gold anticancer metallodrugs. Metalbased anticancer drugs are among the most successful therapeutic. Despite the fact that cisplatin treatment is efficient for. Over the past few decades, transition metal complexes have attracted considerable attention in medicinal inorganic chemistry, especially as synthetic metallonucleases and metalbased anticancer drugs that are able to bind to dna under physiological conditions.
On the medicinal chemistry of gold complexes as anticancer. The optimum antiproliferative activity, observed for the gold complex 3 in u87 mg cells, was found to involve sphase arrest of the cell cycle. A chemicalbiological evaluation of rhodiumi n heterocyclic carbene complexes as prospective anticancer drugs. The results indicate that 3 induces apoptosis through a p53bak pathway, a finding. Goldiii complexes as anticancer agents springerlink. Clinical pharmacology module list of anti cancer drugs. The inhibition activity of a series of anticancer metal complexes based on platinum, ruthenium, and gold metal ions was evaluated on the zincfinger protein parp1, either purified or directly on protein extracts from human breast cancer mcf7 cells.
Consequently, the development of novel metalbased compounds with a pharmacological profile different from that of clinicallyestablished platinum drugs is a. Metalbased anticancer drugs are among the most successful therapeutic agents, as evidenced by the frequent prescription of selected platinum and arsenic compounds to patients. Metallodrugs conjugated to nanocarriers constitute a promising anticancer strategy. Consequently, an increasing number of studies on the potential of gold complexes as anticancer drugs deals with analogues of this compound. An early structureactivity relationship study on 63 auranofin analogues had demonstrated the importance of the phosphine ligand as derivatives lacking this moiety were significantly less active. Farrell virginia commonwealth university, richmond, va, usa 9. Gold complexes as prospective metalbased anticancer drugs v. Review gold complexes as prospective metalbased anticancer drugs. Although their medical applications are the result of serendipitous discoveries, advances in the rational design of metalbased therapeutic agents have become an increasingly important research effort towards the development of new compounds with less toxic side effects and with an understanding. Proteomic approaches in understanding action mechanisms of metalbased anticancer drugs. Gold compounds form a new class of promising metalbased drugs with a number of potential therapeutic applications, particularly in the fields of anticancer and antimicrobial treatments. A new era of metalbased drugs started in the 1960s, heralded by the discovery of potent platinumbased complexes, commencing with cisplatin h. Pioneers of metal based drugs salvarsan drug treatment of syphilis prof. Some of the platinum complexes such as cisplatin, carboplatin, and oxaliplatin are the fdaapproved members of the platinum anticancer drug family.
Metalbased anticancer agents covers the interdisciplinary world of inorganic drug discovery and development by introducing the most prominent compound classes based on different transition metals, discussing emerging. Crude drugs as anticancer agents gold complexes as prospective metalbased anticancer drugs medical and therapeutic value of gold has been recognized thousands of years ago, but its rational use in medicine has not begun until the early 1920s cisplatin is one of the first metalcontaining compounds with anticancer activity. Platinum containing drug anti cancer gold complex gold i and gold iii complexes have long been sought for anticancer treatments. Accessible redox state and ligand substitution make metallodrugs potent treatment candidates. Gold coordination complexes as anticancer agents bentham. This renewed interest is the result of recent studies in which various goldiii complexes have been shown to be stable under physiological conditions and to manifest relevant. Gold nanomaterials as prospective metalbased delivery systems for cancer treatment skip to. Gold i and gold iii complexes, the last isostructural and isoelectronic with platinumii complexes, are potentially attractive as anticancer agents. Goldiii complexes generally exhibit interesting cytotoxic and. Nowadays, compounds of gold and platinum are being used as pharmaceutical drugs. Novel metals and metal complexes as platforms for cancer.
Metal complexes as drugs and chemotherapeutic agents n. Bindoli a, pia m, scutari g, gabbiani c, casini a, messori l. These compounds consist of a gold i center linearly coordinated either to one nheterocyclic carbene nhc and one chloride ligand 1 or to two identical nhc. Several different types can be distinguished, table 31. Towards the rational design of platinumii and gold iii complexes as antitumour agents. The field of inorganic chemistry in medicine may usefully be divided into two main. Antiproliferative characteristics of goldiii compounds. Pincer complexes used in gold compounds can be neutral, mono, or dianionic, and with few exceptions are based on c and n donors. In the past, metalbased compounds were widely used in the treatment of disease conditions, but the lack of clear. In particular, gold i and gold iii complexes have been widely studied and found to have anticancer effects in vitro and in vivo 5, 8, 9. Our lab has also investigated the effects of well defined complexes of pyrrolidine diothiocarbamate complexes containing zinc, znpydtc 2, and copper, cupydtc 2, as potential proteasome inhibitors fig. Goldiii complexes are emerging as a new class of metal complexes with outstanding cytotoxic properties and are presently being evaluated as potential antitumor agents.
Uses of inorganic chemistry in medicine approaches an understanding of the topic in a didactic and systematic manner. Anticancer nheterocyclic carbene complexes of goldiii. Dear colleagues, metalbased complexes represent an important part of the available arsenal of cytotoxic and antiproliferative agents today. Recent advances in mesoporous silica and gold based nanovectors in anticancer drug delivery system volume. Anticancer and antimicrobial metallopharmaceutical agents. Imran ali, sofi danish mukhtar, mohammad nadeem lone, heyam saad ali and hassan y. Metalbased drugs are a commercially important sector of the pharmaceutical business, yet most bioinorganic textbooks lack the space to cover comprehensively the subject of metals in medicine. Cisplatin is one of the first metalcontaining compounds with anticancer activity discovered in the 1960s. Information on the reactivity of the metal complexes with the parp1 zincfinger domain was obtained by highresolution esi fticr mass. The use of metalbased drugs presents the most important strategy in the development of new anticancer and antimicrobial agents. Platinumii complexes, specifically targeting genomic dna e. Gold based probe development and drug discovery remain a burgeoning area of biological research and treatment for disease indications such as cancer 1,2,3,4,5, arthritis 6,7,8,9, and microbial.
Associate professor leung pak hing and his team have discovered that phosphine supported gold complexes have excellent anti tumour activity and clinical trials are likely to begin in the near future. Cisplatin, as one of the leading metalbased drugs, is widely used in the treatment of cancer. These complexes act through a different mechanism as compared to cisplatin. Researchers at the national university of singapore have patented novel gold complexes for use in pharmaceuticals for the treatment of cancer. Chemistry and biology of two novel goldi carbene complexes as prospective anticancer agents. Platinum complexes lobaplatin cisplatin carboplatin nedaplatin oxaliplatin 7 8. Dou 1 1 the prevention program, barbara ann karmanos cancer institute, and department of pathology, school of medicine, wayne state university, detroit, michigan, usa and 2 department of chemical sciences, university of padova, padova, italy. Milacic v, fregona d, dou qp 2008 au complexes as prospective metalbased anticancer drugs. In the following sections, we will provide an overview of different ligand types, with examples of their reactivity. Transition metal complexes bearing amino linked nheterocyclic carbenes nhc were prepared and evaluated for their antiproliferative activities in human cancer cells. Some use of transition metal complexes as anticancer and antihiv agents. With contributions from global leaders in the field, this book will serve as a. Many complexes have displayed interesting anticancer potencies 11.
Recent advances in mesoporous silica and gold based. Highlights metalbased drugs provide attractive chemistries for the design of therapeutics. Metalbased anticancer agents covers the interdisciplinary world of inorganic drug discovery and development by introducing the most prominent compound classes based on different transition metals, discussing emerging concepts and enabling methods, as well as presenting key preclinical and clinical aspects. In addition, copper complexes have been used as anticancer, antiviral, and antibacterial drugs 1, 567891011, reducing the toxicity of the most used metalbased anticancer drugs such. Ehlrich noble prize immunochemistry aurothioglucose sodium aurothiopropanol sulfonate gold complexes chrysotherapy rheumatoid arthritis 6 7. Two novel gold carbene compounds, namely, chlorido 1butyl3methylimidazole2ylidene gold i 1 and bis1butyl3methylimidazole2ylidene gold i 2, were prepared and characterized as prospective anticancer drug candidates. Metal complexes in cancer therapy an update from drug.