Preparation and Biological Properties of Ring-Substituted Naphthalene-1-Carboxanilides

Molecules

Tomas Gonec³  Jiri Kos³  Eoghan Nevin¹  Rodney Govender¹  Matus Pesko⁴  Jan Tengler³  Ivan Kushkevych⁶  Vendula Stastna⁶  Michal Oravec⁵  Peter Kollar⁶  Jim O’Mahony¹  Katarina Kralova²  Aidan Coffey¹ 

[1] Department of Biological Sciences, Cork Institute of Technology, Bishopstown, Cork, Ireland;Institute of Chemistry, Faculty of Natural Sciences, Comenius University, Mlynska dolina Ch-2, 84215 Bratislava, Slovakia;Department of Chemical Drugs, Faculty of Pharmacy, University of Veterinary and Pharmaceutical Sciences, Palackeho 1/3, 61242 Brno, Czech Republic;Department of Environmental Ecology, Faculty of Natural Sciences, Comenius University, Mlynska dolina Ch-2, 84215 Bratislava, Slovakia;Global Change Research Centre AS CR, Belidla 986/4a, 60300 Brno, Czech Republic;Department of Human Pharmacology and Toxicology, Faculty of Pharmacy, University of Veterinary and Pharmaceutical Sciences, Palackeho 1/3, 61242 Brno, Czech Republic

关键词: naphthalene;    lipophilicity;    in vitro antimycobacterial activity;    in vitro cytotoxicity;    photosynthetic electron transport inhibition;    spinach chloroplasts;   

DOI  :  10.3390/molecules190710386

来源: mdpi

【 摘 要 】

In this study, a series of twenty-two ring-substituted naphthalene-1-carboxanilides were prepared and characterized. Primary in vitro screening of the synthesized carboxanilides was performed against Mycobacterium avium subsp. paratuberculosis. N-(2-Methoxyphenyl)naphthalene-1-carboxamide, N-(3-methoxy-phenyl)naphthalene-1-carboxamide, N-(3-methylphenyl)naphthalene-1-carboxamide, N-(4-methylphenyl)naphthalene-1-carboxamide and N-(3-fluorophenyl)naphthalene-1-carboxamide showed against M. avium subsp. paratuberculosis two-fold higher activity than rifampicin and three-fold higher activity than ciprofloxacin. The most effective antimycobacterial compounds demonstrated insignificant toxicity against the human monocytic leukemia THP-1 cell line. The testing of biological activity of the compounds was completed with the study of photosynthetic electron transport (PET) inhibition in isolated spinach (Spinacia oleracea L.) chloroplasts. The PET-inhibiting activity expressed by IC₅₀ value of the most active compound N-[4-(trifluoromethyl)phenyl]naphthalene-1-carboxamide was 59 μmol/L. The structure-activity relationships are discussed.

【 授权许可】

CC BY   
© 2014 by the authors; licensee MDPI, Basel, Switzerland.