Cu(bta)(1,10-phen)ClO4 copper complex modulates the carcinogenicity of carboplatin in somatic cells of Drosophila melanogaster

• Published in: Genetics and molecular biology Vol. 47; no. 3; p. 1
• Main Authors: Lima, Paula Marynella Alves Pereira, Orsonlin, Priscila Capelari, Machado, Nayane Moreira, Oliveira, Rosiane Gomes Silva, Polloni, Lorena, Cruz, Raquel Pereira, Almeida, Janaína do Couto, Oliveira Júnior, Robson José de, Guerra, Wendell, Araújo, Thaise Gonçalves
• Format: Journal Article
• Language: English; Portuguese
• Published: Ribeirao Preto Sociedade Brasileira de Genetica 2024; Sociedade Brasileira de Genética
• Subjects: Antineoplastic drugs; BIOCHEMISTRY & MOLECULAR BIOLOGY; Cancer; Carboplatin; Carcinogenicity; Carcinogens; Chemotherapy; Cisplatin; Copper; copper complexes; Copper compounds; Drosophila melanogaster; Drug development; Drug resistance; Fruit flies; GENETICS & HEREDITY; Genotoxicity; Insects; metal-based drugs; Multidrug resistance; Mutagenesis; Pharmacology; Physiological effects; Side effects; Somatic cells; Tumors; copper complexes; metal-based drugs; chemotherapy; Drosophila melanogaster; Cancer
• ISSN: 1415-4757; 1678-4685; 1678-4685
• DOI: 10.1590/1678-4685-gmb-2023-0366

Chemotherapy stands out as the main systemic treatment strategy against cancer and still faces problems related to multidrug resistance and severe side effects. Copper-based drugs have been widely explored in medicinal chemistry, since copper is an essential metal for physiological activities with antineoplastic effects. In this context, the present study aimed to evaluate the recombinogenic/mutagenic and anticarcinogenic potential of the complex CBP-01 - [Cu(bta)(1,10-phen)ClO4] (Hbta = 4,4,4-trifluoro-1-phenyl-1,3-butanedione and 1,10-phen =1,10-phenanthroline) - through the Somatic and Recombination test (SMART) and the Epithelial Tumor Test (ETT) in Drosophila melanogaster, compared with carboplatin (CARB) and cisplatin (CIS) effects. According to our results, CARB and CIS induced a high frequency of mutant spots, which was not verified at higher concentrations of CBP-01. In addition, CBP-01 exhibited mutagenic/recombinogenic potential only at the lowest concentration and after biometabolization. Subsequently, in the ETT test, CBP-01 did not demonstrate carcinogenic effect. Lastly, epithelial tumors were identified in flies treated with CARB and CIS, which were modulated by the CBP-01 complex. Therefore, CBP-01 modulates genotoxicity of other compounds and is a promising metal-based drug for the development of a new anticancer agent or for optimization of therapeutic regimens.