Medicinal Inorganic Chemistry

Carcinogenesis and Chemotherapy Viewed from the Perspective of Stoichiometric Network Analysis (SNA): What Can the Biological System of the Elements Contribute to an Understanding of Tumour Induction by Elemental Chemical Noxae (e.g., Ni2+, Cd2+) and to an Understanding of Chemotherapy?

“…In the course of tumour formation, it is possible to distinguish between different phases and degrees of "efficiency" in factors that give rise to tumours chemically 6 Boutwell et. al [12] distinguish between normal cells, initiated but dormant tumour cells, and finally those of a 4 Whereas in a comparison of the different species of an element the highest values (i.e., the smallest LD 50 quantities, most pronounced relative toxicities) for acute toxicity are generally found for the aqua ions (apart from alkylated derivatives of the notorious tributyltin or alkyl/aryl mercury cations) or their protolysis products, i.e., in some cases bridged hydroxo species (Al, Cu(II), Pu(IV)), the sequence for carcinogenicity -for example that of nickel -is totally different and not capable of generalization in the above manner [10].…”

“…An example of this is the unspecific cytostatic effect of Ti(IV) complexes [11], which inhibit proteases, probably by attaching themselves to serine residues. 6 The rather complicated way of expressing this stems from the fact that the Boutwell model includes not only oncogenes such as benzo(a)pyrene but also promoters and further substances. It also considers the manner in which these interact.…”

“…The ligands are especially important for absorption, but experience with metal salts shows that they are also significant for acute toxicity and thus tolerance/side effects of the drugs (summarized from Guo and Sadler [6] and other sources):…”

“…A practical example of this would be the blocking of Fe-containing enzymes by gallium(III) salts in chemotherapy [5,6].…”

Redox-active and DNA-binding coordination complexes of clotrimazole

“…These properties can all exert a critical influence on the biological activity and corresponding mechanisms of action [4,5]. For example, some studies have shown that some metal ions generate reactive-oxygen-species (ROS) [6], which although being an inevitable byproduct of cellular respiration, can result in cellular and subcellular oxidative stress and in an altered homeostasis state.…”