This work reports the biological evaluation of a copper complex of the type [Cu(O-O)(N-N)ClO₄], in which O-O = 4,4,4-trifluoro-1-phenyl-1,3-butanedione (Hbta) and N-N = 1,10-phenanthroline (phen), whose generic name is CBP-01. The cytotoxic effect of CBP-01 was evaluated by resazurin assay and cell proliferation was determined by MTT assay. DNA fragmentation was analyzed by gel electrophoresis. Cell cycle progression was detected through propidium iodide (PI) staining. Apoptosis and autophagy were determined by, respectively, Annexin V and 7-AAD staining and monodansylcadaverine (MDC) staining. The changes in intracellular reactive oxygen species levels were detected by DCFDA analysis. The copper complex CBP-01 showed in vitro antitumor activity with IC₅₀s values of 7.4 μM against Sarcoma 180 and 26.4 against murine myoblast cells, displaying selectivity toward the tumor cell tested in vitro (SI > 3). An increase in reactive oxygen species (ROS) generation was observed, which may be related to the action mechanism of the complex. The complex CBP-01 may induce DNA damage leading cells to accumulate at G0/G1 checkpoint where, apparently, cells that are not able to recover from the damage are driven to cell death. Evidence has shown that cell death is initiated by autophagy dysfunction, culminating in apoptosis induction. The search for new metal-based drugs is focused on overcoming the drawbacks of already used agents such as acquired resistance and non-specificity; thus, the results obtained with CBP-01 show promising effects on cancer cells.

The thin line between efficacy and toxicity has challenged cancer therapy. As copper is an essential micronutrient and is important to tumor biology, Cu^II complexes emerged as an alternative to chemotherapy; however, its biological properties need to be better understood. Thus, we report in vitro the antitumor effects of two Cu^II complexes named [Cu(4-fh)(phen)(ClO₄)₂] (complex 1) and [Cu(4-nh)(phen)(ClO₄)₂]·H₂O (complex 2), in which 4-fh = 4-fluorophenoxyacetic acid hydrazide; 4-nh = 4-nitrobenzoic hydrazide and phen = 1,10-phenanthroline. Both complexes presented cytotoxic activity against tumor cells, but only complex 1 showed significant selectivity. Complex 1 also induced DNA-damage, led to G0/G1 arrest and triggered apoptosis, which was initiated by an autophagy dysfunction. The significant in vitro selectivity and the action mechanism of complex 1 are noteworthy and reveal this prodrug as promising for anticancer therapy.

Cancer is the second leading cause of death worldwide. Late diagnosis, low drug selectivity, high toxicity, and treatment resistance are challenges associated with pharmacological interventions. The commonly used therapies include surgery, radiotherapy, hormonal therapy, immunotherapy, and chemotherapy. Recently, Cu complexes have been studied owing to their biological functions and effects on tumor angiogenesis. In this review, we examined 23 types of cancer and revealed the use of cell lines. The synthesis of Cu complexes with ligands such as phenanthroline and thiosemicarbazones has also been reported. Such co-ligation is promising because of its high cytotoxicity and selectivity. Compared with cisplatin, Cu complexes, especially mixed complexes, showed better interactions with DNA, generating reactive oxygen species and inducing apoptosis. Nanoformulations have also been adopted to improve the pharmacological activity of compounds. They enhance the efficacy of complexes by targeting them to the tumor tissue, thereby improving their safety. Studies have also explored Cu complexes with clinically relevant pharmacophores, suggesting a “hybrid chemotherapy” against resistant tumors. Overall, Cu complexes have demonstrated therapeutic versatility, antitumor efficacy, and reduced adverse effects, showing great potential as alternatives to conventional chemotherapy and justifying future clinical investigations to validate their use.

Prostate Cancer (PCa) is the second leading cause of cancer-related deaths among men worldwide. The treatment of advanced cases is based on chemotherapy, which lacks specificity and efficacy, due to severe side effects and resistance to the traditional drugs. Copper complexes have shown antitumoral efficacy and low toxicity, being considered a promising class of metal-based drugs for the treatment of malignant neoplasms. Thus, the present study aimed to evaluate the cellular effects of a copper(II) complex with 4-fluorophenoxyacetic acid hydrazide and 1,10-phenanthroline (1) on PCa cell lines, as well as the mutagenic/recombinogenic and anticarcinogenic potential of 1 in Drosophila melanogaster. PNT-2 (non-tumorigenic), LNCaP (hormone-responsive PCa) and PC-3 (androgen-independent PCa) cells were cultured, and cytotoxicity was assessed using the MTT assay. The expression levels of the proliferation markers Ki-67 and Cyclin D1 were analyzed by flow cytometry. Furthermore, the Somatic Mutation and Recombination Test (SMART) and the Epithelial Tumor Test (ETT) were performed. Complex 1 was selective to LNCaP cells, significantly reducing Ki-67 and Cyclin D1 expression levels. Sub-toxic concentrations of complex 1 were defined by the toxicity test in D. melanogaster, and no mutagenic/recombinogenic/carcinogenic effects were observed. Anticarcinogenic potential was observed in D. melanogaster, suggesting modulating activity of the complex 1 against Doxorubicin, a drug used as control by its carcinogenic properties. Therefore, complex 1 is a possible starting point for the development of new antitumor agents for the treatment of PCa.

Morphological characteristics of pequi fruits (Caryocar brasiliense) allows us to obtain information for the conservation, breeding, and detect genetic variability. Thus, the aims of this research were to characterize the genetic diversity of Caryocar brasiliense that produce fruits with and without thorn at the endocarp; determine the important characters in the study of genetic diversity, and to estimate phenotypic and genotypic correlations. 80 fruits with thorns and 90 fruits without thorns were evaluated. Data were used for analysis: Euclidian distance as a measure of dissimilarity and the Tocher method for delimitation of groups; Principal Component Analysis, and genotypic and phenotypic correlations. Genetic dissimilarity of C. brasiliense ranged from 0.066 (B6-D6) to 0.908 (A14-B3). Tocher method allowed dividing the matrices into three groups, the dendrogram into five groups, and the principal components allowed the distribution in 8 groups. We observed 15 significant correlations for characters of fruit with thorns and 31 correlations for characters of fruit without thorns. The weight of the fruit (with thorns) and the pyrene yield (without thorns) are relevant correlations for production. The groupings generated allowed the classification of the matrices into distinct sets. Allowed the identification of potential producers plants that could be used in breeding programs.