Chlorido and bromido oxaliplatin analogues as potential agents for CRC treatment: Solution behavior, protein binding and cytotoxicity evaluation

• Published in: Inorganica Chimica Acta Vol. 470; pp. 318 - 324
• Main Authors: Marzo, Tiziano, Pratesi, Alessandro, Cirri, Damiano, Pillozzi, Serena, Petroni, Giulia, Guerri, Annalisa, Arcangeli, Annarosa, Messori, Luigi, Gabbiani, Chiara
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 30.01.2018; Elsevier Science Ltd
• Subjects: Anticancer properties; Chemical synthesis; Chemotherapy; Colorectal cancer; Cytotoxicity; DNA interaction; Drugs; Medical treatment; Organic chemistry; Oxaliplatin analogues; Pharmacology; Platinum; Protein interaction; Proteins; Side effects; Toxicity; Oxaliplatin analogues; Chemotherapy; Protein interaction; DNA interaction; Colorectal cancer
• ISSN: 0020-1693; 1873-3255
• DOI: 10.1016/j.ica.2017.05.067

[Display omitted] •Reconsiding oxaliplatin analogues with different halide ligand as potential anticancer agents.•Compounds showed scarce reactivity towards model proteins, while interact extensively with a standard DNA oligo.•Treatments with PtCl2(DACH) and PtBr2(DACH) affect growth of human CRC cells. Despite the widespread use of platinum drugs in the treatment of colorectal cancer (CRC), due to the heavy side effects and to intrinsic or acquired Pt resistance, new and more efficient drugs are urgently needed. Starting from the encouraging results obtained for the complex PtI2(DACH), we summarise here our recent advances, reporting data on the synthesis and the chemical and biological features of two oxaliplatin analogues i.e. PtBr2(DACH) and PtCl2(DACH). The comparative approach of these studies reveals how these analogues possess interesting and differential pharmacological properties as well as some peculiar features that may be conveniently exploited to shed light in the mechanistic aspects involved in the pharmacological action of the parent drug oxaliplatin. Furthermore, these findings may inspire the design of more effective Pt-based anticancer drugs to be used in CRC treatment.