Synthesis and evaluation of a large library of nitroxoline derivatives as pancreatic cancer antiproliferative agents
Pancreatic cancer (PC) is one of the deadliest carcinomas and in most cases, which are diagnosed with
locally advanced or metastatic disease, current therapeutic options are highly unsatisfactory. Based on the
anti-proliferative effects shown by nitroxoline, an old urinary antibacterial agent, we explored a large
library of newly synthesised derivatives to unravel the importance of the OH moiety and pyridine ring of
the parent compound. The new derivatives showed a valuable anti-proliferative effect and some displayed
a greater effect as compared to nitroxoline against three pancreatic cancer cell lines with different genetic
profiles. In particular, in silico pharmacokinetic data, clonogenicity assays and selectivity indexes of the
most promising compounds showed several advantages for such derivatives, as compared to nitroxoline.
Moreover, some of these novel compounds had stronger effects on cell viability and/or clonogenic capacity
in PC cells as compared to erlotinib, a targeted agent approved for PC treatment.