Synthesis and Systematic Investigation of Lepidiline A and Its Gold(I), Silver(I), and Copper(I) Complexes Using In Vitro Cancer Models and Multipotent Stem Cells
The imidazole alkaloid lepidiline A from the root of Lepidium meyenii has a moderate to low in vitro anticancer effect. Our aim was to extend cytotoxicity investigations against a panel of cancer cells, including multidrug-resistant cancer cells, and multipotent stem cells. Lepidiline A is a N-heterocyclic carbene precursor, therefore a suitable ligand source for metal complexes. Thus, we synthesized lepidiline A and its copper(I), gold(I), and silver(I) complexes and tested them against ovarian, gastrointestinal, breast, and uterine cancer cells and bone marrow-derived and adipose-derived mesenchymal stem cells. Lepidiline A and its copper complex demonstrated moderate cytotoxicity, while silver and gold complexes exhibited significantly enhanced and consistent cytotoxicity against both cancer and stem cell lines. ABCB1 in the multidrug-resistant uterine sarcoma line conferred significant resistance against lepidiline A and the copper-lepidiline A complex, but not against the silver and gold complexes. Our results indicate that only the copper complex induced a significant and universal increase in the production of reactive oxygen species within cells. In summary, binding of metal ions to lepidiline A results in enhanced cytotoxicity with the nature of the metal ion playing a critical role in determining its properties.
Szilárd Tóth, Márton F Szlávik, Réka Mandel, Fanni Fekecs, Gábor Tusnády, Flóra Vajda, Nóra Varga, Ágota Apáti, Attila Bényei, Attila Paczal, András Kotschy, Gergely Szakács
2024
Synthesis and Systematic Investigation of Lepidiline A and Its Gold (I), Silver (I), and Copper (I) Complexes Using In Vitro Cancer Models and Multipotent Stem Cells S Tóth, MF Szlávik, R Mandel, F Fekecs, G Tusnády, F Vajda, N Varga, … ACS omega 9 (29), 32226-32234