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Synthesis of novel nitroxoline analogs with potent cathepsin B exopeptidase inhibitory activity

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Abstract
Nitroxoline, a well‐known antimicrobial agent, has been identified in several independent studies, and on different molecular targets, as a promising candidate to be repurposed for cancer treatment. One specific target of interest concerns cathepsin B, a lysosomal peptidase involved in the degradation of the extracellular matrix (ECM), leading to tumor invasion, metastasis and angiogenesis. However, dedicated optimization of the nitroxoline core is needed to actually deliver a nitroxoline‐based antitumor drug candidate. Within that context, 34 novel nitroxoline analogs were synthesized and evaluated for their relative cathepsin B inhibitory activity, their antiproliferative properties and their antimicrobial activity. More than twenty analogs were shown to exert a similar or even slightly higher cathepsin B inhibitory activity compared to nitroxoline. The implemented modifications of the nitroxoline scaffold and the resulting SAR information can form an eligible basis for further optimization toward more potent cathepsin B inhibitors in the quest for a clinical nitroxoline‐based antitumor agent.
Keywords
Antitumor agents, Cancer, Cathepsin B, Drug Repurposing, Nitroxoline, IN-VITRO, ESCHERICHIA-COLI, OCCLUDING LOOP, PROTEASES, SUSCEPTIBILITY, ANGIOGENESIS, GROWTH

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MLA
Van de Walle, Tim, et al. “Synthesis of Novel Nitroxoline Analogs with Potent Cathepsin B Exopeptidase Inhibitory Activity.” CHEMMEDCHEM, 2020, doi:10.1002/cmdc.202000402.
APA
Van de Walle, T., Briand, M., Mitrović, A., Sosič, I., Gobec, S., Kos, J., … D’hooghe, M. (2020). Synthesis of novel nitroxoline analogs with potent cathepsin B exopeptidase inhibitory activity. CHEMMEDCHEM. https://doi.org/10.1002/cmdc.202000402
Chicago author-date
Van de Walle, Tim, Marina Briand, Ana Mitrović, Izidor Sosič, Stanislav Gobec, Janko Kos, Leentje Persoons, et al. 2020. “Synthesis of Novel Nitroxoline Analogs with Potent Cathepsin B Exopeptidase Inhibitory Activity.” CHEMMEDCHEM. https://doi.org/10.1002/cmdc.202000402.
Chicago author-date (all authors)
Van de Walle, Tim, Marina Briand, Ana Mitrović, Izidor Sosič, Stanislav Gobec, Janko Kos, Leentje Persoons, Dirk Daelemans, Steven De Jonghe, Zorica Ubiparip, Tom Desmet, Kristof Van Hecke, Sven Mangelinckx, and Matthias D’hooghe. 2020. “Synthesis of Novel Nitroxoline Analogs with Potent Cathepsin B Exopeptidase Inhibitory Activity.” CHEMMEDCHEM. doi:10.1002/cmdc.202000402.
Vancouver
1.
Van de Walle T, Briand M, Mitrović A, Sosič I, Gobec S, Kos J, et al. Synthesis of novel nitroxoline analogs with potent cathepsin B exopeptidase inhibitory activity. CHEMMEDCHEM. 2020;
IEEE
[1]
T. Van de Walle et al., “Synthesis of novel nitroxoline analogs with potent cathepsin B exopeptidase inhibitory activity,” CHEMMEDCHEM, 2020.
@article{8671561,
  abstract     = {Nitroxoline, a well‐known antimicrobial agent, has been identified in several independent studies, and on different molecular targets, as a promising candidate to be repurposed for cancer treatment. One specific target of interest concerns cathepsin B, a lysosomal peptidase involved in the degradation of the extracellular matrix (ECM), leading to tumor invasion, metastasis and angiogenesis. However, dedicated optimization of the nitroxoline core is needed to actually deliver a nitroxoline‐based antitumor drug candidate. Within that context, 34 novel nitroxoline analogs were synthesized and evaluated for their relative cathepsin B inhibitory activity, their antiproliferative properties and their antimicrobial activity. More than twenty analogs were shown to exert a similar or even slightly higher cathepsin B inhibitory activity compared to nitroxoline. The implemented modifications of the nitroxoline scaffold and the resulting SAR information can form an eligible basis for further optimization toward more potent cathepsin B inhibitors in the quest for a clinical nitroxoline‐based antitumor agent.},
  author       = {Van de Walle, Tim and Briand, Marina and Mitrović, Ana and Sosič, Izidor and Gobec, Stanislav and Kos, Janko and Persoons, Leentje and Daelemans, Dirk and De Jonghe, Steven and Ubiparip, Zorica and Desmet, Tom and Van Hecke, Kristof and Mangelinckx, Sven and D'hooghe, Matthias},
  issn         = {1860-7179},
  journal      = {CHEMMEDCHEM},
  keywords     = {Antitumor agents,Cancer,Cathepsin B,Drug Repurposing,Nitroxoline,IN-VITRO,ESCHERICHIA-COLI,OCCLUDING LOOP,PROTEASES,SUSCEPTIBILITY,ANGIOGENESIS,GROWTH},
  language     = {eng},
  pages        = {15},
  title        = {Synthesis of novel nitroxoline analogs with potent cathepsin B exopeptidase inhibitory activity},
  url          = {http://dx.doi.org/10.1002/cmdc.202000402},
  year         = {2020},
}

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