Toxic Effects of Metallopharmaceuticals

Abstract

Discovery of the metallopharmaceutical cisplatin and its use in antitumour therapy has initiated the rational design and screening of metal-based anticancer agents as potential chemotherapeutics. In addition to the achievements of cisplatin and its therapeutic analoguesThe wide use of metallopharmaceuticals in contemporary oncology dates to the discovery of cisplatin by Rosenberg and coworkers in 1965 (1). This discovery opened the gate to the unexplored world of metal-based chemotherapeutic agents, which have different pharmacokinetic, pharmacodynamic and pharmacological mechanisms of action than do conventional organic drugs (2). Today, there are many successful metallopharmaceuticals that are primarily used in clinical trials not just to treat cancer but to fight a range of diseases, including parasitic and bacterial infections (3). Over the past several decades, several cisplatin analogues have been screened as potential antitumour agents, but of these, only two (carboplatin and oxaliplatin) have entered worldwide clinical use (4). The clinical use of

“Half-Sandwich” Ruthenium Complexes with Alizarin as Anticancer Agents: In Vitro and In Vivo Studies

“…Anticancer agents present clinical concerns with their systemic toxicity. Among the side effects, neurotoxicity, vascular toxicity, nephrotoxicity, and ototoxicity are the most common . Therefore, overcoming the unpleasant side effects is a major challenge concerning new anticancer agents.…”

“…The cardiotoxicity, one of the most common side effects of anticancer agents, was analyzed in the zebrafish embryos at 48 h after exposure to the compounds (Figure B). As expected, a normal embryonic heart rate was recorded for the control (without complexes and solvent) and solvent groups, at 162 ± 24 and 167 ± 21 beats min –1 , respectively.…”

“…As shown in Figure 9A, only exposure of the zebrafish embryos to C2 at low concentration did not cause neurotoxicity. The SCF is an important parameter of neurotoxicity because spontaneous tail coiling is the first motor activity as a consequence of innervation of the muscle by the developing nervous network, 82 which could reflect a morphological effect or even mortality. 82 Therefore, hatching failure and morphological change, including delayed growth, somite, and tail malformation, in embryos and mortality can be related to the neurotoxic effect of the compounds.…”

“…The SCF is an important parameter of neurotoxicity because spontaneous tail coiling is the first motor activity as a consequence of innervation of the muscle by the developing nervous network, 82 which could reflect a morphological effect or even mortality. 82 Therefore, hatching failure and morphological change, including delayed growth, somite, and tail malformation, in embryos and mortality can be related to the neurotoxic effect of the compounds. The cardiotoxicity, one of the most common side effects of anticancer agents, 82 was analyzed in the zebrafish embryos at 48 h after exposure to the compounds (Figure 9B).…”

“…82 Therefore, hatching failure and morphological change, including delayed growth, somite, and tail malformation, in embryos and mortality can be related to the neurotoxic effect of the compounds. The cardiotoxicity, one of the most common side effects of anticancer agents, 82 was analyzed in the zebrafish embryos at 48 h after exposure to the compounds (Figure 9B). As expected, a normal embryonic heart rate was recorded for the control (without complexes and solvent) and solvent groups, at 162 ± 24 and 167 ± 21 beats min −1 , respectively.…”