Cargando…

Quinoline‐Conjugated Ruthenacarboranes: Toward Hybrid Drugs with a Dual Mode of Action

The role of autophagy in cancer is often complex, ranging from tumor‐promoting to ‐suppressing effects. In this study, two novel hybrid molecules were designed, containing a ruthenacarborane fragment conjugated with a known modulator of autophagy, namely a quinoline derivative. The complex closo‐[3‐...

Descripción completa

Detalles Bibliográficos
Autores principales: Gozzi, Marta, Murganic, Blagoje, Drača, Dijana, Popp, John, Coburger, Peter, Maksimović‐Ivanić, Danijela, Mijatović, Sanja, Hey‐Hawkins, Evamarie
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6973020/
https://www.ncbi.nlm.nih.gov/pubmed/31675152
http://dx.doi.org/10.1002/cmdc.201900349
Descripción
Sumario:The role of autophagy in cancer is often complex, ranging from tumor‐promoting to ‐suppressing effects. In this study, two novel hybrid molecules were designed, containing a ruthenacarborane fragment conjugated with a known modulator of autophagy, namely a quinoline derivative. The complex closo‐[3‐(η (6)‐p‐cymene)‐1‐(quinolin‐8‐yl‐acetate)‐3,1,2‐RuC(2)B(9)H(10)] (4) showed a dual mode of action against the LN229 (human glioblastoma) cell line, where it inhibited tumor‐promoting autophagy, and strongly inhibited cell proliferation, de facto blocking cellular division. These results, together with the tendency to spontaneously form nanoparticles in aqueous solution, make complex 4 a very promising drug candidate for further studies in vivo, for the treatment of autophagy‐prone glioblastomas.