Complexes of metals other than platinum as antitumour agents

Abstract

The earliest reports on the therapeutic use of metals or metal-containing compounds in cancer and leukemia date from the sixteenth and nineteenth centuries. They were forgotten until the 1960s, when the anti-tumour activity of the inorganic complex cis-diammine-dichloroplatinum(II) (cisplatin) was discovered. This led to the development of other types of non-organic cytostatic drugs. Cisplatin has developed into one of the most frequently used and most effective cytostatic drugs for the treatment of solid carcinomas. Numerous other metal compounds containing platinum, other platinum metals, and even non-platinum metals were then shown to be effective against tumours in man and experimental tumours in animals. These compounds comprise main-group metallic compounds of gallium, germanium, tin, and bismuth, early-transition metal complexes of titanium, vanadium, niobium, molybdenum, and rhenium, and late-transition metal complexes of ruthenium, rhodium, iridium, platinum, copper, and gold. Several platnium complexes and four non-platnium-metal antitumour agents have so far entered early clinical trials. Gallium trinitrate and spirogermanium have already passed phase II clinical studies and have shown limited cytostatic activity against certain human carcinomas and lymphomas. The two early-transition metal complexes budotitane and titanocene dichloride have just reached the end of phase I clinical trials and have been found to have an unusual pattern of organ toxicity in man. Titanocene dichloride will soon enter phase II clinical studies.

Gold(III) compound is a novel chemocytotoxic agent for hepatocellular carcinoma

“…7 Although cisplatin was effective in treating metastatic nasopharyngeal carcinoma 8,9 and prolonged survival in advanced and metastatic non-small cell lung cancer, 10 its overall response rates in HCC patients were low, and thus it failed to prolong patient survival. 11 Therefore, novel and nontoxic therapeutic agents are urgently needed to treat HCC.…”

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?

“…After reduction to As(III) or V(IV) they also intervene in other biochemical processes; As(III), for example, is bound very strongly to the sulphur sites of thiolates (e.g., cysteine). 5 German law on chemicals already has no levels that may be regarded as harmless for carcinogenic substances such as benzene; this is in contrast to "merely" toxic substances (like hydrogen cyanide) for which MAK (maximum workplace concentration) and MIK (atmospheric concentration close to the ground) values are defined in the context of occupational medicine. But here there is a prospect of identifying particularly dangerous carcinogens theoretically in advance on the strength of their mode of action.…”

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

“…The relationships and any dynamics that may result (occurrence of spontaneous, uncontrolled oscillations in the intracellular autocatalytic cycle as a possible cause of chemically induced tumours) are discussed formally with the aid of SNA. The focus of this study is on metal ions 4 and some of their complexes and compounds in their role as both carcinogens 5 and cytostatic drugs.…”

The synthesis, chemical and biological properties of dichlorido(azpy)gold(III) chloride (azpy= 2-(phenylazo)pyridine) and the gold-induced conversion of the azpy ligand to the chloride of the novel tricyclic pyrido[2,1-c][1,2,4]benzotriazin-11-ium cation

“…The search for an agent with increased anticancer activity still remains an elusive goal; that is why different metal-coordinated compounds have also been studied. Metal-based compounds with titanium, rhodium, rhenium, ruthenium, gallium, gold, tin, cobalt and copper have been synthesized and many of them have shown promising in vitro anticancer results [7].…”