Bioactivity of Methoxylated and Methylated 1-Hydroxynaphthalene-2-Carboxanilides: Comparative Molecular Surface Analysis
Hana Michnová,
Šárka Pospíšilová,
Tomáš Goněc,
Iva Kapustíková,
Peter Kollár,
Violetta Kozik,
Robert Musioł,
Izabela Jendrzejewska,
Ján Vančo,
Zdeněk Trávníček,
Alois Čížek,
Andrzej Bąk,
Josef Jampílek
Affiliations
Hana Michnová
Division of Biologically Active Complexes and Molecular Magnets, Regional Centre of Advanced Technologies and Materials, Faculty of Science, Palacký University, Šlechtitelů 27, 78371 Olomouc, Czech Republic
Šárka Pospíšilová
Division of Biologically Active Complexes and Molecular Magnets, Regional Centre of Advanced Technologies and Materials, Faculty of Science, Palacký University, Šlechtitelů 27, 78371 Olomouc, Czech Republic
Tomáš Goněc
Department of Chemical Drugs, Faculty of Pharmacy, University of Veterinary and Pharmaceutical Sciences, Palackého třída 1/3, 61242 Brno, Czech Republic
Iva Kapustíková
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Comenius University, Odbojárov 10, 83232 Bratislava, Slovakia
Peter Kollár
Department of Human Pharmacology and Toxicology, Faculty of Pharmacy, University of Veterinary and Pharmaceutical Sciences, Palackého třída 1/3, 61242 Brno, Czech Republic
Violetta Kozik
Institute of Chemistry, University of Silesia, Szkolna 9, 40007 Katowice, Poland
Robert Musioł
Institute of Chemistry, University of Silesia, Szkolna 9, 40007 Katowice, Poland
Izabela Jendrzejewska
Institute of Chemistry, University of Silesia, Szkolna 9, 40007 Katowice, Poland
Ján Vančo
Division of Biologically Active Complexes and Molecular Magnets, Regional Centre of Advanced Technologies and Materials, Faculty of Science, Palacký University, Šlechtitelů 27, 78371 Olomouc, Czech Republic
Zdeněk Trávníček
Division of Biologically Active Complexes and Molecular Magnets, Regional Centre of Advanced Technologies and Materials, Faculty of Science, Palacký University, Šlechtitelů 27, 78371 Olomouc, Czech Republic
Alois Čížek
Department of Infectious Diseases and Microbiology, Faculty of Veterinary Medicine, University of Veterinary and Pharmaceutical Sciences, Palackého třída 1/3, 61242 Brno, Czech Republic
Andrzej Bąk
Institute of Chemistry, University of Silesia, Szkolna 9, 40007 Katowice, Poland
Josef Jampílek
Division of Biologically Active Complexes and Molecular Magnets, Regional Centre of Advanced Technologies and Materials, Faculty of Science, Palacký University, Šlechtitelů 27, 78371 Olomouc, Czech Republic
A series of twenty-six methoxylated and methylated N-aryl-1-hydroxynaphthalene- 2-carboxanilides was prepared and characterized as potential anti-invasive agents. The molecular structure of N-(2,5-dimethylphenyl)-1-hydroxynaphthalene-2-carboxamide as a model compound was determined by single-crystal X-ray diffraction. All the analysed compounds were tested against the reference strain Staphylococcus aureus and three clinical isolates of methicillin-resistant S. aureus as well as against Mycobacterium tuberculosis and M. kansasii. In addition, the inhibitory profile of photosynthetic electron transport in spinach (Spinacia oleracea L.) chloroplasts was specified. In vitro cytotoxicity of the most effective compounds was tested on the human monocytic leukaemia THP-1 cell line. The activities of N-(3,5-dimethylphenyl)-, N-(3-fluoro-5-methoxy-phenyl)- and N-(3,5-dimethoxyphenyl)-1-hydroxynaphthalene-2-carbox- amide were comparable with or even better than the commonly used standards ampicillin and isoniazid. All promising compounds did not show any cytotoxic effect at the concentration >30 µM. Moreover, an in silico evaluation of clogP features was performed for the entire set of the carboxamides using a range of software lipophilicity predictors, and cross-comparison with the experimentally determined lipophilicity (log k), in consensus lipophilicity estimation, was conducted as well. Principal component analysis was employed to illustrate noticeable variations with respect to the molecular lipophilicity (theoretical/experimental) and rule-of-five violations. Additionally, ligand-oriented studies for the assessment of the three-dimensional quantitative structure−activity relationship profile were carried out with the comparative molecular surface analysis to determine electron and/or steric factors that potentially contribute to the biological activities of the investigated compounds.
