Ruthenium complexes show promise when submitted to toxicological safety tests using alternative methodologies
Thallita Monteiro Teixeira1, Isabela Gasparini Arraes2, Davi Carvalho Abreu2
1Instituto de Ciências Biológicas, Universidade Federal de Goiás (UFG), CEP 74045-155, Goiânia, GO, Brazil; Aquatic Ecology and Toxicology, Center for Organismal Studies, University of Heidelberg, D-69117, Heidelberg, Germany.
European Journal of Medicinal Chemistry
|March 12, 2021
Summary
Two new ruthenium complexes with Lapachol and Lawsone ligands show promise as anticancer agents, exhibiting selective toxicity against cancer cells with reduced genotoxicity and acute toxicity in zebrafish embryos.
Area of Science:
- Coordination Chemistry
- Medicinal Chemistry
- Toxicology
Background:
- Rising global cancer incidence necessitates novel treatments with fewer side effects.
- Ruthenium complexes are emerging as potential chemotherapeutic agents due to their low toxicity and tumor selectivity.
Purpose of the Study:
- To synthesize, characterize, and evaluate the biological properties of two new ruthenium (II) complexes.
- To assess the cytotoxic and toxicological profiles of these complexes against various cancer and non-tumor cell lines and in zebrafish embryos.
Main Methods:
- Synthesis and characterization of two ruthenium (II) complexes: [Ru(Law)(dppb)(phen)]PF6 and [Ru(Lap)(dppb)(phen)]PF6.
- In vitro cytotoxicity assays (MTT, neutral red) against human and murine cancer cell lines.
- In vitro genotoxicity assays (micronucleus, comet assay) and in vivo acute toxicity tests in zebrafish embryos.
Main Results:
- Both complexes exhibited weak interaction with CT-DNA and moderate interaction with BSA.
- Complexes demonstrated significant selectivity indices for the HeLa tumor line (1.17 and 10.91).
- Complex (1) showed lower genotoxic potential and reduced sublethal effects in zebrafish embryos compared to complex (2), which caused lethality.
Conclusions:
- The synthesized ruthenium complexes display potential as anticancer agents with notable selectivity.
- In vitro and zebrafish embryo models offer valuable toxicological data, reducing reliance on animal experimentation.
- Further investigation is warranted to explore the therapeutic potential of these ruthenium complexes.
