20.500.12556/DiRROS-19722 Addition of 2-(ethylamino)acetonitrile group to nitroxoline results in significantly improved anti-tumor activity in vitro and in vivo Lysosomal cysteine peptidase cathepsin B, involved in multiple processes associated with tumor progression, is validated as a target for anti-cancer therapy. Nitroxoline, a known antimicrobial agent, is a potent and selective inhibitor of cathepsin B, hence reducing tumor progression in vitro and in vivo. In order to further improve its anti-cancer properties we developed a number of derivatives using structure-based chemical synthesis. Of these, the 7-aminomethylated derivative (compound 17) exhibited significantly improved kinetic properties over nitroxoline, inhibiting cathepsin B endopeptidase activity selectively. In the present study, we have evaluated its anti-cancer properties. It was more effective than nitroxoline in reducing tumor cell invasion and migration, as determined in vitro on two-dimensional cell models and tumor spheroids, under either endpoint or real time conditions. Moreover, it exhibited improved action over nitroxoline in impairing tumor growth in vivo in LPB mouse fibrosarcoma tumors in C57Bl/6 mice. Taken together, the addition of a 2-(ethylamino)acetonitrile group to nitroxoline at position 7 significantly improves its pharmacological characteristics and its potential for use as an anti-cancer drug. nitroxoline derivative cathepsin B inhibition tumor invasion cell migration true false true Angleški jezik Ni določen Neznano 2024-07-24 03:47:32 2024-07-26 12:47:01 2024-07-27 04:00:54 0000-00-00 00:00:00 2017 0 0 Nasl. z nasl. zaslona; Opis vira z dne 9. 8. 2017; str. 59136-59147 no. 35 Vol. 8 2017 0000-00-00 Zaloznikova Objavljeno NiDoloceno 0000-00-00 0000-00-00 2017-07-17 577.2 1949-2553 10.18632/oncotarget.19296 4360305 RAZ_Mitrovic_Ana_2017.pdf RAZ_Mitrovic_Ana_2017.pdf 1 D122E245A831A4E6A8A2A7DE4054FBC4 4e2de2567ca6d1ba3b6a7a7b02c3deaeca5e417d85d6ff4ed0c30aeed38b9792 bd4cd21b-4b24-11ef-b487-001a4af901a5 https://dirros.openscience.si/Dokument.php?lang=slv&id=27593 https://doi.org/10.18632/oncotarget.19296 0 92bc8703-49b2-11ef-b487-001a4af901a5 https://dirros.openscience.si/Dokument.php?lang=slv&id=27395 Nacionalni inštitut za biologijo 0 0 0