**3. Conclusion**

674 Pharmacology

NSAID (ibuprofen, naproxen, tolmetin, and diclofenac), with a carboxylic function have been studied by means of infrared and Raman spectroscopy. All NSAIDs bind to the metal through the carboxylate group. The spectroscopic data support the formation of dimeric

The preparation and properties of the Cu(II) complex Cu(SAS)2.H2O are reported for the antiinflammatory drug Salsalate (SAS) (Underhill et al, 1989). The complex is reported to exhibit an increased superoxide dismutase activity compared with the parent drug molecule in the nitroblue tetrazolium assay. Weder and friends synthesized Cu(II) indomethacin

Drugs belonging to the non-steroidal anti-inflammatory drug group (NSAID) are not only used as anti-inflammatory and analgesic agents, but also exhibit chemopreventive and chemosuppressive effects on various cancer cell lines (Roy et al, 2006). They exert their anticancer effects by inhibiting both at the protein level and/or at the transcription level. Cu(II) complexes of these NSAIDs show better anti-cancer effects than the bare drugs. UV-Visible spectroscopy was used to characterize the complexation between Cu(II) and two NSAIDs belonging to the oxicam group, piroxicam and meloxicam, both of which exhibit anticancer properties. For the first time, this study shows that, Cu(II)-NSAID complexes can directly bind with the DNA backbone, and the binding constants and the stoichiometry or the binding site sizes have been determined. Thermodynamic parameters from van't Hoff plots showed that the interaction of these Cu(II)-NSAID complexes with ctDNA is an entropically driven phenomenon. Circular dichroism spectroscopy showed that the binding of these Cu(II)- NSAIDs with ctDNA result in DNA backbone distortions which is similar for both Cu(II) piroxicam and Cu(II)-meloxicam complexes. Competitive binding with a standard intercalator like ethidium bromide (EtBr) investigated by circular dichroism spectroscopy as well as fluorescence measurements indicate that the Cu(II)-NSAID complexes could intercalate in the

Inspired from Sorenson's studies, new investigations on formation and synthesis of Cu(II) complexes with antiinflammatory drugs were carried out as well as Zn(II) complexes, where some of them are ternary complexes (Anlanmert et al, 2010). The formation conditions and constants of Cu(II)-tryptophan-aspirin and Zn(II)-tryptophan-aspirin ternary complexes in aqueous solutions were determined using potentiometric method to provide chemical data for the synthesis, considering the synergistic capability of aspirin, the antiinflammatory activity of Cu(II), the synergistic effect of tryptophan-aspirin combination in migraine and in diseases which cause immune activation, the stronger analgesic, antiinflammatory and antithrombotic effect of Cu(II)-aspirinate and Zn(II)-aspirinate than aspirin, decreased gastrointestinal toxicity of Cu(II)-aspirinate and Zn(II)-aspirinate than aspirin, the stronger analgesic and antiinflammatory effects of some Cu(II)-amino acid complexes than Cu(II) aspirinate and the increased bioavailability of Zn(II)-amino acid complexes. The effects of leucine in cancer, wound healing and regulation of glucose in blood, anticancer activity and healing activity of Cu(II) on radiation effects, antiinflammatory effects of Cu(II)-aspirin and Cu(II)-amino acid compounds, sinergistic activity of aspirin and its anticancer effect which was proved in recent years are known (Anlanmert, 2006). Under the light of these effects, the formation of Cu(II)-leucine-aspirin was also investigated using potentiometric and spectrophotometric method. The anticancer action and wound healing effect on skin cancers

group behaves as a bridging bidentate ligand.

[Cu2L4(H2O)2] complexes in which the COO-

complexes (Weder et al, 1999).

DNA.

In this chapter, clinical uses of organometallic complexes and some prominent studies on new therapeutic complexes were mentioned. Developments in explorations of organometallic compounds, in various therapeutic areas continue to be an active and productive area of research. Increasingly powerful tools, notably spectroscopic techniques like time-resolved infrared are used for identifying and structurally characterizing the solid complex, optical spectroscopic and potentiometric methods are used for monitoring intermediates and species in solution. Besides these preclinical and clinical studies are significantly enhancing our knowledge and understanding of the structure and mechanistic aspects of the therapeutic organometallic complexes.

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**30** 

*Canada* 

**Aging: Drugs to Eliminate Methylglyoxal,** 

The aging process not only affects the whole body, but also affects individual cells. While the age-related changes in the body are popularly recognized as wrinkling of the skin, indicating alterations in basement membrane proteins, the processes of cellular aging are less well defined. The underlying common theme of cellular aging and whole body aging seems to be an increase in oxidative stress. Advanced glycation endproducts (AGEs), which are widely accepted to alter basement membrane proteins, also increase oxidative stress. Reactive dicarbonyls, such as methylglyoxal (MG), formed during glycolysis and other metabolic processes are precursors of AGEs formation and triggers of oxidative stress. MG, AGEs and oxidative stress are very likely to induce DNA damage and be at the root of cellular aging. Thus, a strategy to prevent an elevation of MG, formation of AGEs and the associated oxidative stress has great therapeutic potential to slow the aging process at the

The process of aging is accepted as an inevitable normal part of the life cycle of each and every living organism. Aging can be grossly defined as an overall decline in biological functions. Thus, aging involves gradual changes in the body such as reduced immunity, loss of muscle strength, stiffening of the arterial wall, loss of elasticity and wrinkling of the skin, and decline in memory, all of which result in increasing weakness, risk of developing diseases, and ultimately death. These changes take place at the cellular, organ and the whole organism level. The whole process of aging unfolds very clearly in species with a long life span such as human

Hayflick et al. [1] first described cellular senescence in the sixties when they showed that normal cells had a limited ability to proliferate in culture. Cellular senescence is believed to be initiated by increased cellular stress [2, 3]. Factors contributing to cellular stress and aging include dysfunctional telomeres (telomere length) [4, 5], DNA damage [6] and mitogenic or oncogenic stimuli and signals [2, 4, 5]. The factors such as age and oxidative

beings. Cellular aging ultimately translates into whole body aging.

**1. Introduction** 

cellular and the whole body level.

**2. The ageing process** 

**a Reactive Glucose Metabolite, and** 

**Advanced Glycation Endproducts** 

Indu Dhar and Kaushik Desai

*Department of Pharmacology, College of Medicine, University of Saskatchewan, Saskatoon, SK,* 

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