Cancer prevention

Studies as early as 1969 suggested that there was an inverse correlation between dietary selenium levels and cancer mortality rates.45 Accompanying the discovery of the enzyme GPx, the chemopreventative action of selenium was initially attributed to its presence in anti-oxidant enzymes such as GPx and other selenoproteins. In 1996 Clark found that selenium supplementation, 200 mg day in the form of selenium-enriched yeast, reduced the risk of prostate, colon and lung cancer by up to 48 in...

Antioxidants and antiinflammatory agents

Reactive oxygen species (ROS) are involved in many biological processes including the inflammatory response. ' ' Ebselen (1) is an anti-oxidant and anti-inflammatory that has undergone Phase III clinical trials as a neuroprotective agent and is soon to become the first synthetic organoselenium therapeutic released on the market. Selenium is not liberated from Ebselen 1, and as such it is relatively non-toxic. The anti-inflammatory action of Ebselen 1 is attributed to its ability to interfere...

Mechanism of Action of Cisplatin

Broadening the chemotherapeutic arsenal depends on understanding existing agents with a view toward developing new modes of attack. In the 35 years since the discovery of the anti-tumor activity of cisplatin, laboratory studies have provided considerable information as to how the drug exerts its antitumor effects and how some tumors are, or become, resistant to this drug. Although a number of features of the mechanism underlying the anti-tumor effects of cisplatin have been thoroughly...

Bipolar disorder and schizophrenia

As described above, lithium inhibits GSK-3 and inositol phosphate signalling and both pathways have therefore been suggested to be involved in BD. The best current hypothesis describing how lithium functions in the treatment of BD is the 'inositol depletion' hypothesis of Berridge et al.40 This theory suggests that the cause of BD may be overactive InsP signalling in the brain of these patients, and this may be reduced by the inhibitory effect of lithium on InsP signalling (Figure 1.4). In...

Copper Thiosemicarbazone Complexes

The anti-tumour potential of quinonoidal compounds is known since 1974 and several 1,2-napthaquinone derivatives behave as anti-cancer compounds.26 28 Recently, the synthesis and structural characterization of metal conjugates of 1,2-naphthaquinone (NQTS, Scheme 12.2) along with their anti-tumour activities against the MCF7 breast cancer cell line have been studied.29 Thiosemi-carbazonates have been intensively studied due to their inhibitory action on the DNA enzyme ribonucleotide diphosphate...

Gestational hypertension preeclampsia and eclampsia

Gestational hypertension is the most frequent cause of hypertension during pregnancy and the rate varies between 6 and 17 .14,15 Some women with gestational hypertension will subsequently progress to preeclampsia and the rate of progression depends on gestational age at the time of diagnosis. The rate reaches 50 when gestational hypertension develops before 30 weeks gestation. Preeclampsia is primarily defined as gestational hypertension plus proteinuria. Preeclampsia is considered severe if...

Boron Compounds as Therapeutic

Geeta Rana, Kamesh Vyakaranam, John A. Maguire and Narayan S. Hosmane 2.1 Boron Neutron Capture Therapy 19 2.2 Classes of Boron Compounds for Potential Use 2.2.2 Boron-containing amino acids and related peptides 24 2.2.3 Boron-containing nucleic acid precursors 27 2.3 Phosphates, Phosphonates and Phosphoramidates 31 2.5 Boron Analogues of Pyrophosphates 33 2.6 Boronated Polyamines 34 2.9 Lipids and Phospholipids 37 2.10 Radiation Sensitizers 38 2.11 Cyclic Thiourea Derivatives 38 2.12 Central...

Antihypertensives

May and co-workers have developed a series of phenylaminoethylselenides (PAESe) 19 that have anti-hypertensive properties.105 107 PAESe's antihypertensive activities appear to result from inhibition of dopamine -mono-oxygenase (DBM).105 DBM catalyzes the conversion of dopamine to noradrenalin and is dependent on ascorbate for catalytic activity (Figure 17.6). PAESes inhibit DBM by depleting ascorbate in the vesicles of chromaffin cells. DBM oxidizes PAESe 19 to the selenium oxide 20 using...

Titanocene Dichloride

7.5.1 Chemistry and anti-cancer activity In 1979, Kopf and Kopf-Maier reported42 on the first metallocene with antitumor activity, the complex Cp2TiIVCl2 (bis( -cyclopentadienyl)titanium(IV) dichloride, titanocene dichloride). The red crystalline titanium(IV) complex was first prepared by Wilkinson and Birmingham in 1954.43 The two planar C5H5 cyclopentadienyl rings each have a delocalized negative charge and are coordinated to the metal center via pentahapto metal carbon coordination in a...

Antitumor Activity of Carboplatin Oxaliplatin and Nedaplatin

The leaving group of carboplatin is a less labile cyclobutanedicarboxylato ligand which undergoes a slower rate of aquation than the chlorides in cisplatin. Unfortunately, carboplatin exhibits cross-resistance with cisplatin so that although less toxic and more easily administered than cisplatin, it has not demonstrated any substantial advantages over cisplatin.4,5 The therapeutic index defined by the efficacy versus toxicity profile even favors cisplatin in most tumor systems (in testis,...

Toxic Side Effects of As2O3

In the treatment of APL patients, the side effects of As2O3 appear to be mild. In contrast to many other chemotherapeutic agents, it causes no myelosuppression. Instead, As2O3 induces leukocytosis in about 50 of patients.11,13,36 The leuko-cytosis can resolve in all cases without chemotherapy.87 The APL patients on As2O3 can also develop retinoic acid syndrome (RAS)-like symptoms such as fever, skin rash and edema, which can be readily relieved by steroid administra-tion.88 Other mild effects...

Budotitane

7.4.1 Chemistry and anti-cancer activity The TiIV(bzac)2(OEt)2 complex (budotitane, bzac 1-phenylbutane-1,3-dionate benzoylacetonate) was the first non-platinum complex tested in clinical trials.18 Budotitane and related bis( -diketonato) metal complexes can be synthesized from the corresponding metal tetrahalogenides and the diketonates in an anhydrous organic solvent. Budotitane was selected from about 300 related derivatives for further development. The structure activity relation of...

Titanium Anticancer Drugs

After the discovery of the tumor-inhibiting properties of cis-diammine dichloro-platinum(II) (cisplatin) in 196912 and its routine use as a leading cytostatic drug since 1979,13 there has been increasing interest in the development of new anti-tumor metal agents including non-platinum metal complexes. Among these, two monomeric titanium(IV) complexes have qualified for clinical trials (Figure 7.1) TiIV(bzac)2(OEt)2 (budotitane) and Cp2TiIVCl2 (titanocene dichloride). Relevant reviews on...

Nitrogen and other donor atoms

The cyclopalladate complexes of imidazoline (Imd) derivatives PdCl2 (C6H5CH2C3H5N2)2 and PdCl(SEt2)(C6H4-C3H5-N2)2 exhibited important cytotoxic activity against HL-60, with IC50 values, lower than 10 mg ml, close to those of cis-DDP and considerably higher than the free ligand. Thus, the cytotoxic activity of free Imd increased upon coordination with Pd(II).41 Two diastereomeric cyclopalladated complexes arising from Pd2(mpba)2(m-OAc)2 (mpba is 4-methoxy-benzoylbenzylideneimine, Figure 21.8b)...

Examples where introduction of ferrocene has resulted in enhanced activity or a change in activity profile

The replacement of one of the phenyl rings in tamoxifen by ferrocene has given rise to a group of compounds called ferrocifens.24,25,26 Tamoxifen is a selective estrogen receptor modulator that is used against breast cancer. Its activity is limited to 'estrogen receptor positive' tumours that constitute about 60 of breast cancer cases. The ferrocifens were synthesized in an attempt to overcome the shortcomings of tamoxifen as an anti-tumour agent. The triphenylethylene-like framework of...

Mechanism of Action of Carboplatin Oxaliplatin and Nedaplatin

Carboplatin forms a similar spectrum of DNA adducts as cisplatin with slightly different sequence preferences.22 Concentrations of carboplatin approximately two orders of magnitude higher are needed to obtain DNA platination levels equivalent to cisplatin. Conformational alterations induced in DNA by carbo-platin in cell-free media have been characterized23 and the changes of non-denaturational character similar to those observed for cisplatin at the same level of DNA platination have been...

References

Xavier (Ed.), Frontiers in Bioinorganic Chemistry, VCH, Weinheim, 1986. 2. H. Sigel and A. Sigel, J. Indian Chem. Soc., 77, 501-509 (2000). 3. H. Sigel (Ed.), Metal Ions in Biological Systems, M. Dekker, Inc., New York, Vol. 11, 1980. 4. B.K. Kepler (Ed.), Metal Complexes in Cancer Chemotherapy, VCH, Weinheim, 1993. 5. A. Sigel and H. Sigel (Eds), Metal Ions in Biological Systems, M. Dekker, Inc., New York, Vol. 32, 1996. 6. Z. Guo and P.J. Sadler, Angew. Chem. Int. Ed., 38, 1512-1531...

Humans

Manganese deficiency in humans is uncommon but it has been reported in several laboratory-induced experiments.16 The first was by Doisey who inadvertently fed a low-manganese diet (0.34mg day) for 3.5 months to a subject on a semi-purified vitamin K-deficient diet. Symptoms that were not ameliorated by restoration of vitamin K were reddening of a black beard and hair, diminished hair and nail growth, hypocholesterolemia and a scaly, transitory dermatitis. The last two symptoms were observed...

Introduction

The German chemist Winkler,1,2 working at the Freiberg Academy of Mines, was able to isolate during the investigation of the then-discovered mineral argyrodite Ag6GeS5, containing 5 to 7 germanium a new element in its free state. He called the new element germanium in honour of his motherland. Germanium atomic number 32, atomic weight 72.59, melting point 937.4, boiling point 2830 C , a greyish-white lustrous crystalline metal, belongs to family 14 of periodic table formerly called group IVA ,...

Applications of antimony drugs as antileishmanial agents

Antimony-based drugs have remained the major therapeutic treatment in the clinic for decades.19 The use of antimony chemotherapy increases the survival rate of those patients with Leishmania infection to over 90 .20 Although its main action is concentrated only on the visceral leishmaniasis, other forms of the disease are also responsive. The major disadvantages are a long treatment period, requiring hospitalization, and the need in many cases for subsequent course of treatment for an effective...

RhodiumIII complexes

As rhodium III coordination complexes have a d6 electronic configuration, they are isoelectronic with Ru II and Pt IV complexes which are interesting anti-tumor complexes, e.g. OC-6-43 - PtCl2 OOCMe 2 CyNH2 NH3 Cy cyclohexyl JM216 , an orally active anti-tumor agent. Rhodium III complexes generally have an octahedral structure and are inert complexes nevertheless, many of the Rh III coordination complexes tested show considerable anti-tumor and anti-microbial activity. The meridional complex...

Copper Purine Derivatives Complexes

The synthesis, characterization and biological anti-tumour and anti-proliferative activity of new mononuclear or binuclear copper II complexes with 6- 2-chlorobenzyl-amino purine HL1 A and 6- 3-chlorobenzylamino purine HL2 B Scheme 12.1 have been reported by Travnycek etal.,22 the composition of the complexes depending on the molar ratio of the reactants and the pH of the medium. The mononuclear complex Cu H L2 2Cl3 Cl H2O 1 was isolated and green-blue crystals suitable for single-crystal X-ray...

Antibacterial and Antiparasitic Activity

Many Rh I , Rh II and Rh III complexes are active against malaria, leish-maniasis, trypanosomes, bacteria and algae. The anti-malarial activity of RhCl COD CQ CQ chloroquine is similar to that of chloroquine diphosphate.79,80 However, chloroquine complexes with other metals ruthenium and gold are more active.79 Numerous rhodium complexes were investigated for the treatment of leishmaniasis.79,81 83 Rhodium III cationic complexes containing 2-hydroxybenzothiazole are very efficient...

PalladiumII complexes with Schiff base ligands

Schiff base complexes of Pd II , derived by the template condensation of 2,3-diamino-1,4-naphthoquinone and 1,2-dibromoethane in ethanol L Figure 21.5 , of formula Pd L Br2 2H2O,22 together with the corresponding Mn II complex were synthesized and tested for anti-bacterial activity, against B. cereus and other G and G strains.22 The complexes were more active than sodium penicillin against B. cereus. The Pd II complex showed good activity against G strains. Azole thiazolo and triazolo...

Cancer

Cancer is a malignant tumor that occurs as a result of abnormal and uncontrolled cellular divisions. Manganese may be critical in the development of some cancers as tumor cells usually have low concentrations of SOD2 and ROS play a role in tumor formation. Also, transfection with SOD2 enhances cellular differentiation and inhibits malignant transformation.12,51 A Mn salen mimetic of superoxide dismutase and catalase EUK-135 has been found to exert pharmacologic efficacy in cell survival...

Targeting Cells with GdIII Chelates

Currently, an important task in the field consists of providing the CAs with targeting capabilities. After the implementation of extracellular and blood pool systems, the new frontier in MRI is represented by the possibility of imaging molecular targets that act as signatures of a given pathology. This will allow early diagnosis of diseases as the detection of an altered biochemical process largely anticipates the anatomical changes that are at the basis of current diagnostic modalities....

Germatranes

The next group of biologically active organogermanium compounds are germatranes 3 - tricyclic organogermanium derivatives of triethanolamine containing a hypervalent germanium atom with a transannular bond to nitrogen bond length 2.01-2.29 A which is responsible for their chemical stability.122 Several methods for the preparation of germatranes have been elaborated. The reaction of tetra-alkoxy- or trialkoxy-germatranes with triethanolamine occurring under mild conditions in the presence of a...