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Quinoline‐Conjugated Ruthenacarboranes: Toward Hybrid Drugs with a Dual Mode of Action
Author(s) -
Gozzi Marta,
Murganic Blagoje,
Drača Dijana,
Popp John,
Coburger Peter,
MaksimovićIvanić Danijela,
Mijatović Sanja,
HeyHawkins Evamarie
Publication year - 2019
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.201900349
Subject(s) - autophagy , quinoline , mode of action , in vivo , conjugated system , chemistry , derivative (finance) , cell culture , stereochemistry , combinatorial chemistry , biochemistry , biology , apoptosis , organic chemistry , genetics , microbiology and biotechnology , financial economics , economics , polymer
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.