Complex Formation Reactions of (N, N'-Dimethylethylenediamine) Palladium (II) With Various Biologically Relevant Ligands (original) (raw)
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New trends in platinum and palladium complexes as antineoplastic agents
Coordination Chemistry Reviews, 2016
The discovery of cisplatin (cis-Pt(NH3)2Cl2) as an antineoplastic agent has focused attention on the rational design of metal complexes that can be potentially used in cancer chemotherapy. Today, the pharmaceutical industry invests more than $1 billion each year in the development of new metalbased drugs to improve biological activities, in terms of cellular selectivity, therapeutic efficiency and minimization of side effects. Chemotherapies based on transition metals play a key role in cancer treatment, and among them platinum and palladium are the most fruitful. This article reviews the main recent advances in the design and synthesis of platinum-and palladium-based drugs, their structural features and biological studies of them. The rationale for the choice of the ligand, related to leaving groups, the geometry of the complex and the oxidation state of the metal ion, is discussed. An overview of the main biological techniques and approaches for testing the interaction of these molecules with the biological environment, mainly DNA, to validate the effect is also provided.
Novel Palladium Complex: Cytotoxicity against Cisplatin-resistant K562 Cells
Iranian Journal of Pharmaceutical Research : IJPR, 2019
Today, development of resistance to anticancer drugs (including cisplatin) is noticed as a major problem. Recently several studies demonstrated that palladium complexes showed remarkable cytotoxic effects against K562 cell line and could be used efficiently for treatment of many human cancers including leukemia. Hereof, K562 cells were made resistant to cisplatin using increasing concentration of cisplatin up to 4.5 mM and then cytotoxic effect of synthesized palladium complex was evaluated on this sub-line using MTT assay. Annexin V/PI staining using flow cytometry and scanning electron microscopy (SEM) were performed to find out the mechanism of the observed cytotoxicity. Results indicated that tested compounds had a noticeable cytotoxic effect on K562 cells 80 times more than cisplatin. Palladium complex also showed significant cytotoxicity on resistant K562 sub-line. Flow cytometry and SEM results revealed that these compounds exert their cytotoxic effect via apoptosis and it co...
Journal of Cancer Research and Clinical Oncology, 2011
Purpose Treatment for lung cancer is still far from satisfying rates. Therefore, there is a need for novel anticancer agents. For this purpose, novel platinum and palladium complexes {[Pd(sac)(terpy)](sac)·4H 2 O (Complex 1), [Pt(sac)(terpy)] (sac)·5H 2 O (Complex 2), [PdCl(terpy)](sac)·2H 2 O (Complex 3), [PtCl(terpy)](sac)·2H 2 O (Complex 4)} have been tested against three diVerent non-small cell lung cancer cell lines (A549, H1299, PC-3).
2005
In modern cancer therapy the clinical application of platinum-based drugs is more and more limited by the occurrence of intrinsic or acquired resistances. In this context the potential use of dinuclear platinum complexes in chemotherapy is increasingly relevant. The novel complexes Pd(Bzdpa)Cl 2 , Pd 2 (C 4 H 8 (dpa) 2 )Cl 4 , and Pt 2 (C 4 H 8 (dpa) 2 )Cl 4 allow a direct comparison of mono-and dinuclear palladium and platinum complexes respectively deriving from a 2,2Ј-dipyridylamine (Hdpa) ligand system. They were characterized by single crystal X-ray analysis as well as infrared spectroscopy and elemental analysis. The cisplatin analogous mononuclear palladium complex Pd(Bzdpa)Cl 2 (1) (Bzdpa: (2,2Јdipyridylbenzyl)amine) belongs to a range of 2,2Ј-dipyridylaminebased compounds which were extensively studied in our laborato-
Organometallics, 2018
Cisplatin is an efficient anticancer drug, but its effects are often lost after several chemotherapy cycles, showing important secondary effects. For these reasons, new anticancer agents, with different coordination properties and mechanisms of action, are needed. Here we describe the reaction of 2phenylaniline with cis-[PtCl2(dmso)2] and sodium acetate to afford a cycloplatinated compound 2 and the synthesis and some biological studies of 3−6 (two neutral and two ionic compounds):
European Journal of Medicinal Chemistry, 2012
Novel platinum and palladium complexes with (2-isopropoxyphenyl)dicyclohexylarsine and (2methoxyphenyl)dicyclohexylarsine ligands were synthesized and tested on different tumor cells. Adducts with general formula MX 2 L 2 (M ¼ Pt(II), Pd(II); X ¼ Cl or I; L ¼ organoarsenic ligand) were fully characterized. According to the crystallographic data, in all complexes the organoarsenic ligands coordinate the metal center through the arsenic atom only, in a trans arrangement with the halogen atoms. The antiproliferative potential of complexes 1e4 was evaluated in vitro on human tumor cell lines. A markedly biological activity was observed against the chemoresistant hepatic tumor stem cell line, the normal hepatic stem cells and towards the hepatocellular carcinoma (non-stem) cells. The new compounds toxicity is selectively limited in normal liver cells, unlikeness with the oxaliplatin, which displays a more intense effect in normal cells, compared with the two tumor cell lines. The stem cells treatment with compounds 1e4 causes DNA damages; the antimitotic effect of these compounds is based on their genotoxicity and on the capacity to form crosslinks with the DNA interstrand. In the case of platinum complexes 1 and 3 this mechanism gives rise to specific lesions on DNA that induces apoptosis in stem cells, influencing their selectivity in tumor cell growth inhibition. Compounds 1, 2 and 4 display higher activity against tumor stem cells. The novel platinum complexes 1 and 3 are more efficient against tumor stem cells than oxaliplatin, and if used in combination with sorafenib-based monoclonal anticancer therapy, complexes 1, 3 and 4 have the ability to induce superior chemosensitivity relative to sorafenib than the standard platinum-based drug, making them promising candidates for prodrug development.
Cancer Chemotherapy and Pharmacology, 2008
Introduction Cisplatin (cis-diamminedichloroplatinum) was first identified for its anti-bacterial activity, and was later also shown to be an efficient anticancer agent. However, the therapeutic use of this anticancer drug is somewhat limited by its toxic side effects, which include nephrotoxicity, nausea, and vomiting. Furthermore the development of drug-resistant tumours is commonly observed following therapy with cisplatin. Hence there is a need for improved platinum derived drugs to overcome these limitations. Aims Apoptosis contributes significantly to the cytotoxic effects of anticancer agents such as cisplatin; therefore in this study the potential anticancer properties of a series of pyrazole palladium(II) and platinum(II) complexes, [(3,5-R2pz)2PdCl2] {R = H (1), R = Me (2)} and [(3,5-R2pz)2PtCl2] {R = H (3), R = Me (4)}, were evaluated by assessment of their pro-apoptotic activity. Methods The induction of apoptosis was measured in CHO cells by the detection of phosphatidylserine (PS) exposure using the annexin V and APOPercentage™ assays; DNA fragmentation using the Terminal deoxynucleotide transferase dUTP Nick End Labelling (TUNEL) assay; and the detection of activated caspase-3. Results The platinum complexes were shown to be considerably more active than the palladium complexes, with complex 3 demonstrating the highest level of cytotoxic and pro-apoptotic activity. The LD50 values for complex 3 and cisplatin were 20 and 70 μM, respectively, demonstrating that the cytotoxic activity for complex 3 was three times higher than for cisplatin. Various human cancer cell lines, including CaSki, HeLa, as well as the p53 mutant Jurkat T cell line were also shown to be susceptible to complex 3. Conclusions Collectively, this in vitro study provides insights into action of palladium and platinum complexes and demonstrates the potential use of these compounds, and in particular complex 3, in the development of new anticancer agents.
Platinum Complexes as Anticancer Agents
Recent Patents on Anti-cancer Drug Discovery, 2006
The application of inorganic chemistry to medicine is a rapidly developing field, and novel therapeutic and diagnostic metal complexes are now having an impact on medical practice. Advances in biocoordination chemistry are crucial for improving the design of compounds to reduce toxic side effects and understand their mechanisms of action. Cisplatin, as one of the leading metal-based drugs, is widely used in the treatment of cancer. Significant side effects and drug resistance, however, have limited its clinical applications. Biological carriers conjugated to cisplatin analogs have improved specificity for tumor tissue, thereby reducing side effects and drug resistance. Platinum complexes with distinctively different DNA binding modes from that of cisplatin also exhibit promising pharmacological properties. This review focuses on recent advances in developing platinum anticancer agents with an emphasis on platinum coordination complexes.
Turkish Journal of Chemistry, 2023
Introduction Cancer, which is a complex disease characterized by uncontrolled cell proliferation, is the second largest cause of mortality in the world [1, 2]. Among other cancer types hepatocellular carcinoma (HCC), which is the most common type of primary liver cancer in adults, was the third most common cause of cancer deaths in 2020 in the world [3]. The highest incidence and the lowest survival rate after treatment for HCC was observed in Asia and sub-Saharan Africa where hepatitis B infection is endemic [4]. It is foreseen that new cancer cases will increase significantly in the next decades [4-7]. There are many types of cancer treatment options which are usually very complex and they are developing gradually. Among them are chemotherapy, surgery, and radiation therapy. Chemotherapy entails use of special drugs to kill cancer cells and has been recently supported by new methods of treatment such as immunotherapy to give successful results. However, chemotherapeutics have many negative side effects which compromises effectiveness of this treatment method. Therefore, recently increasing importance and efforts are devoted to development of more effective chemotherapeutic drugs with fewer side effects [8,9]. Metal-based compounds have attracted much attention since cis-platin was discovered by Barnett Rosenberg in 1960 and they have been used widely in treatment of various cancer types, especially of head and neck, ovarian and colorectal cancers. Today, cis-platin and its derivatives (i.e. carboplatin and oxaliplatin) are still extensively used in cancer treatment [10]. However, these compounds have major disadvantages such as the limitation of their efficacy to some cancer types as well as their extensive side effects [11]. Hence, recently new studies on other metal complexes have increased. Among these metal complexes, cost effective palladium complexes have attracted much attention as they form compounds similar to platinum [12]. Studies revealed that palladium (II) complexes have considerable anticancer activity on various cancer cell lines [13]. The many different types of Pd (II) complexes (i.e. monomeric, dimeric, tetrameric, cyclo-palladated, palladacyclic, and heterobimetallic) were reported to have cytotoxic activity and the pyridine, pyrazole, quinoline and,