Non Platinum Metal Complexes as Anti‐cancer Drugs

Abstract

The development of metal complexes with platinum central atoms such as cisplatin or carboplatin had an enormous impact on current cancer chemotherapy. However, the spectrum of cancers that can be treated with platinum agents is narrow and treatment efficacy suffers from side effects and resistance phenomena. These unresolved problems in platinum-based anti-cancer therapy have stimulated increased research efforts in the search for novel non platinum-containing metal species as cytostatic agents. Preclinical and clinical investigations showed that the development of new metal agents with modes of action different from cisplatin is possible. Thus, complexes with iron, cobalt, or gold central atoms have shown promising results in preclinical studies and compounds with titanium, ruthenium, or gallium central atoms have already been evaluated in phase I and phase II trials. This review covers some relevant examples of preclinical and clinical research on novel non platinum metal complexes.

Cisplatin administration influences on toxic and non-essential element metabolism in rats

“…New platinum complexes (CPA-1, CPA-7, Pt(IV)Cl 4 ) block STAT3 activity in vitro at low micromolar concentrations. Contrary to other reports on cisplatin, no significant effects of these novel platinum(IV) complexes were observed on ERK1/2, p38, JNK, Akt and Jaks, suggesting that direct modulation of these signaling proteins may not contribute to the biological effects of CPA-1, CPA-7, and Pt(IV)Cl 4 [4,5,6,7].…”

Ruthenium(II) phosphine/diimine/picolinate complexes: Inorganic compounds as agents against tuberculosis

“…Owing to their wide spectrum of coordination numbers and geometries, as well as kinetic properties, metal compounds offer mechanisms of drug action that cannot be realized by organic agents [7,8]. Ruthenium compounds have already exhibited potential anti-tumour activity since the 1970s and 1980s, and, more recently, the Ru(III) complexes NAMI-A and KP 1019 (FFC14a) have entered clinical trials.…”

Studies on the cytotoxic, apoptotic and antitumoral effects of Au(III) and Pt(II) complexes of 1, 10-phenanthroline on V79 379A and A549 cell lines

“…Several studies demonstrated that the complexes of Cu and phen have apoptotic effect 30 . Additionally, the palladium(II) complex of the unsubstituted 1,10-phenanthroline, Pd(phen) 2 In an attempt to explore the molecular mechanism underlying the observed cytotoxic response, DAPI staining and caspase-3 colorimetric enzyme assays were conducted. DAPI staining data of the present study revealed that [Au(phen)Cl 2 ]Cl and Pt(phen)Cl 2 induced apoptosis on both dose-dependent cell lines (Figures 3 and 4).…”

“…The compound was characterized by IR, 2 The mixture of (phen)1,10-phenanthroline solution in EtOH-H 2 O and K 2 PtCl 4 in H 2 O was stirred at 30°C for 8 h. The precipitate was filtered and washed several times with water and diethylether, and then dried in vacuum desiccator. The compound was characterized by IR, 1 H-NMR and MASS spectroscopic data.…”

“…Metals or metal containing compounds are known to be important agents for therapy in cancer and leukemia, dating back to the sixteenth century 1 . Since Rosenberg discovered the antitumor activity of cisplatin (Cis-diaminedichloroplatinum(II)) in 1967, it is the mainstay of treatment for testicular, ovarian, bladder, cervical, small-cell and non-small-cell lung cancers [2][3][4][5] . The success of cisplatin as an anticancer drug prompted medical researchers to use metals, including platinum derivatives such as carboplatin, oxoplatin, nedaplatin, lobaplatin, ruthenium and gold compounds in anticancer medicine 2,3,5,6 .…”