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

喹啉偶联的钌碳硼烷:迈向具有双重作用机制的混合药物

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Abstract

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.

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