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. 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 compounds as new family of anticancer drugs. Dear colleagues, metalbased complexes represent an important part of the available arsenal of cytotoxic and antiproliferative agents today. These complexes act through a different mechanism as compared to cisplatin. Cancer treatment using gold in treatment of cancer. Imran ali, sofi danish mukhtar, mohammad nadeem lone, heyam saad ali and hassan y.
Pioneers of metal based drugs salvarsan drug treatment of syphilis prof. Highlights metalbased drugs provide attractive chemistries for the design of therapeutics. 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. 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. Platinum containing drug anti cancer gold complex gold i and gold iii complexes have long been sought for anticancer treatments. Towards the rational design of platinumii and gold iii complexes as antitumour agents. The optimum antiproliferative activity, observed for the gold complex 3 in u87 mg cells, was found to involve sphase arrest of the cell cycle.
Metalbased anticancer drugs are among the most successful therapeutic agents, as evidenced by the frequent prescription of selected platinum and arsenic compounds to patients. Novel metals and metal complexes as platforms for cancer. Goldiii complexes generally exhibit interesting cytotoxic and. Despite the fact that cisplatin treatment is efficient for. These metal complexes contain nheterocyclic carbene nhc ligands which are able to form strong. 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. Anticancer and antimicrobial metallopharmaceutical agents. 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. Metal complexes as drugs and chemotherapeutic agents n. Metallodrugs conjugated to nanocarriers constitute a promising anticancer strategy. A new era of metalbased drugs started in the 1960s, heralded by the discovery of. Gold complexes and their anticancer properties springerlink.
Metalbased anticancer drugs are among the most successful therapeutic. Ehlrich noble prize immunochemistry aurothioglucose sodium aurothiopropanol sulfonate gold complexes chrysotherapy rheumatoid arthritis 6 7. In the past, metalbased compounds were widely used in the treatment of disease conditions, but the lack of clear. 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. Some use of transition metal complexes as anticancer and antihiv agents. Clinical pharmacology module list of anti cancer drugs. 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. Consequently, the development of novel metalbased compounds with a pharmacological profile different from that of clinicallyestablished platinum drugs is a. Uses of inorganic chemistry in medicine approaches an understanding of the topic in a didactic and systematic manner. 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. Platinumii complexes, specifically targeting genomic dna e. Gold coordination complexes as anticancer agents bentham. The use of metalbased drugs presents the most important strategy in the development of new anticancer and antimicrobial agents. Goldiii complexes as anticancer agents springerlink.
The field of inorganic chemistry in medicine may usefully be divided into two main. Gold complexes as prospective metalbased anticancer drugs. Some of the platinum complexes such as cisplatin, carboplatin, and oxaliplatin are the fdaapproved members of the platinum anticancer drug family. 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. 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. This perspective covers the recent contributions of the che laboratory to the development of transitionmetalbased anticancer complexes, including gold, platinum, ruthenium and iron complexes. Recent advances in mesoporous silica and gold based nanovectors in anticancer drug delivery system volume. Goldiii complexes are emerging as a new class of metal complexes with outstanding cytotoxic properties and are presently being evaluated as potential antitumor agents. 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.
Significant side effects and drug resistance, however, have limited its clinical applications. 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. Dolores fregonas research works university of padova. Many complexes have displayed interesting anticancer potencies 11. Cisplatin, as one of the leading metalbased drugs, is widely used in the treatment of cancer. 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.
Current progresses in metalbased anticancer complexes as. Chemistry and biology of two novel goldi carbene complexes as prospective anticancer agents. Information on the reactivity of the metal complexes with the parp1 zincfinger domain was obtained by highresolution esi fticr mass. A chemicalbiological evaluation of rhodiumi n heterocyclic carbene complexes as prospective anticancer drugs. Anticancer nheterocyclic carbene complexes of goldiii. The area of gold complexes with anticancer activity has developed fast. Accessible redox state and ligand substitution make metallodrugs potent treatment candidates. With contributions from global leaders in the field, this book will serve as a. Recent advances in mesoporous silica and gold based. 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. Bindoli a, pia m, scutari g, gabbiani c, casini a, messori l.
The results indicate that 3 induces apoptosis through a p53bak pathway, a finding. Farrell virginia commonwealth university, richmond, va, usa 9. Cisplatin is one of the first metalcontaining compounds with anticancer activity discovered in the 1960s. Platinum complexes lobaplatin cisplatin carboplatin nedaplatin oxaliplatin 7 8. Researchers at the national university of singapore have patented novel gold complexes for use in pharmaceuticals for the treatment of cancer. Joe gerald jesu raj, devendra deo pathak, pramesh n. Antiproliferative characteristics of goldiii compounds. Metal complexes in cancer therapy an update from drug design perspective umar ndagi, ndumiso mhlongo, mahmoud e soliman molecular modelling and drug design research group, school of health sciences, university of kwazulunatal, westville, durban, south africa abstract. A new era of metalbased drugs started in the 1960s, heralded by the discovery of potent platinumbased complexes, commencing with cisplatin h. Medicinal chemistry of gold anticancer metallodrugs.
Metal properties offer a wide range of coordination numbers. Several different types can be distinguished, table 31. In the following sections, we will provide an overview of different ligand types, with examples of their reactivity. New trends for metal complexes with anticancer activity. Consequently, an increasing number of studies on the potential of gold complexes as anticancer drugs deals with analogues of this compound. Gold nanomaterials as prospective metalbased delivery systems for cancer treatment skip to. Gold complexes as prospective metalbased anticancer drugs v. Milacic v, fregona d, dou qp 2008 au complexes as prospective metalbased anticancer drugs.
Proteomic approaches in understanding action mechanisms of metalbased anticancer drugs. Currently, metallodrugs with anticancer activity, especially gold and platinum complexes, have an enormous impact on clinical cancer chemotherapy. Review gold complexes as prospective metalbased anticancer drugs. A further indepth analysis on the therapeutic potential of gold complexes as anticancer drugs has recently been published. 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. 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. 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. Pincer complexes used in gold compounds can be neutral, mono, or dianionic, and with few exceptions are based on c and n donors. Department of chemistry, college of science, taibah university, almedina almunawara 41477, department of chemistry, jamia millia islamia. On the medicinal chemistry of gold complexes as anticancer.