Ring-substituted 1-hydroxynaphthalene-2-carboxanilides were previously investigated for their antimycobacterial properties. In our study, we have shown their antiproliferative and cell death-inducing effects in cancer cell lines. Cell proliferation and viability were assessed by WST-1 assay and a dye exclusion test, respectively. Cell cycle distribution, phosphatidylserine externalization, levels of reactive oxygen or nitrogen species (RONS), mitochondrial membrane depolarization, and release of cytochrome c were estimated by flow cytometry. Levels of regulatory proteins were determined by Western blotting. Our data suggest that the ability to inhibit the proliferation of THP-1 or MCF-7 cells might be referred to meta- or para-substituted derivatives with electron-withdrawing groups -F, -Br, or -CF3 at anilide moiety. This effect was accompanied by accumulation of cells in G1 phase. Compound 10 also induced apoptosis in THP-1 cells in association with a loss of mitochondrial membrane potential and production of mitochondrial superoxide. Our study provides a new insight into the action of salicylanilide derivatives, hydroxynaphthalene carboxamides, in cancer cells. Thus, their structure merits further investigation as a model moiety of new small-molecule compounds with potential anticancer properties.

Department of Chemical Drugs Faculty of Pharmacy Masaryk University Palackeho tr 1946 1 612 42 Brno Czech Republic

Department of Cytokinetics Institute of Biophysics of the Czech Academy of Sciences Kralovopolska 135 612 65 Brno Czech Republic

Department of Human Pharmacology and Toxicology Faculty of Pharmacy University of Veterinary and Pharmaceutical Sciences Brno Palackeho tr 1946 1 612 42 Brno Czech Republic

Department of Pharmacology and Toxicology Faculty of Pharmacy Masaryk University Palackeho tr 1946 1 612 42 Brno Czech Republic

Institute of Neuroimmunology Slovak Academy of Sciences Dubravska cesta 9 845 10 Bratislava Slovakia

Institute of Pharmacology of Natural Products and Clinical Pharmacology Ulm University Helmholtzstraße 20 89081 Ulm Germany

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New potent N-hydroxycinnamamide-based histone deacetylase inhibitors suppress proliferation and trigger apoptosis in THP-1 leukaemia cells

Salicylanilides and Their Anticancer Properties

Hybridization Approach to Identify Salicylanilides as Inhibitors of Tubulin Polymerization and Signal Transducers and Activators of Transcription 3 (STAT3)

Consensus-Based Pharmacophore Mapping for New Set of N-(disubstituted-phenyl)-3-hydroxyl-naphthalene-2-carboxamides