Journal
ANTIBIOTICS-BASEL
Volume 11, Issue 8, Pages -Publisher
MDPI
DOI: 10.3390/antibiotics11081010
Keywords
camphorimine complexes; cytotoxic activity; toxicity; PIXE; ROS
Categories
Funding
- FCT-Fundacao para a Ciencia e a Tecnologia [UIDB/00100/2020, UIDP/00100/2020, UID/MULTI/04349/2019, UI/BD/152244/2021]
- FCT-Fundacao para a Ciencia e a Tecnologia through projects of the Research Unit Institute for Bioengineering and Biosciences-iBB [UIDB/04565/2020, UIDP/04565/2020]
- FCT-Fundacao para a Ciencia e a Tecnologia through Associate Laboratory Institute for Health and Bioeconomy-i4HB [LA/P/0140/2020]
- Fundação para a Ciência e a Tecnologia [UI/BD/152244/2021] Funding Source: FCT
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This study assessed the cytotoxic activity of camphorimine complexes based on Cu(I), Cu(II), Ag(I), and Au(I) metal sites against ovarian cancer cells. The results showed that the gold complexes exhibited the highest activity, followed by the silver complexes, and then the copper complexes. It was also found that the Ag(I) and Au(I) camphorimine complexes had higher cytotoxic activity than cisplatin. Furthermore, the camphorimine complexes had minimal interaction with DNA compared to cisplatin. The cytotoxic activity of the complexes was directly related to cellular uptake and inversely related to ROS formation.
The cytotoxic activity of four sets of camphorimine complexes based on the Cu(I), Cu(II), Ag(I), and Au(I) metal sites were assessed against the cisplatin-sensitive A2780 and OVCAR3 ovarian cancer cells. The results showed that the gold complexes were ca. one order of magnitude more active than the silver complexes, which in turn were ca. one order of magnitude more active than the copper complexes. An important finding was that the cytotoxic activity of the Ag(I) and Au(I) camphorimine complexes was higher than that of cisplatin. Another relevant aspect was that the camphorimine complexes did not interact significantly with DNA, in contrast with cisplatin. The cytotoxic activity of the camphorimine complexes displayed a direct relationship with the cellular uptake by OVCAR3 cells, as ascertained by PIXE (particle-induced X-ray emission). The levels of ROS (reactive oxygen species) formation exhibited an inverse relationship with the reduction potentials for the complexes with the same metal, as assessed by cyclic voltammetry. In order to gain insight into the toxicity of the complexes, their cytotoxicity toward nontumoral cells (HDF and V79 fibroblasts) was evaluated. The in vivo cytotoxicity of complex 5 using the nematode Caenorhabditis elegans was also assessed. The silver camphorimine complexes displayed the highest selectivity coefficients (activity vs. toxicity).
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