Antibacterial and Herbicidal Activity of Ring-Substituted 3-Hydroxynaphthalene-2-carboxanilides

Jiri Kos,Iveta Zadrazilova,Tomas Gonec,Stanislava Keltosova,Katarina Kralova,Alois Cizek,Pavel Bobal,Jan Tengler,Peter Kollar,Tereza Kauerova,Michal Oravec,Josef Jampilek,Matus Pesko

doi:10.3390/molecules18077977

Abstract

In this study, a series of twenty-two ring-substituted 3-hydroxy-N-phenylnaphthalene-2-carboxanilides were prepared and characterized. The compounds were tested for their activity related to inhibition of photosynthetic electron transport (PET) in spinach (Spinacia oleracea L.) chloroplasts. Primary in vitro screening of the synthesized compounds was also performed against four Staphylococcus strains and against two mycobacterial species. 3-Hydroxy-N-(2-methoxyphenyl)naphthalene-2-carboxamide showed high biological activity (MIC = 55.0 µmol/L) against S. aureus as well as methicillin-resistant strains. N-(2-Fluorophenyl)-3-hydroxynaphthalene-2-carboxamide showed higher activity (MIC = 28.4 µmol/L) against M. marinum than the standard isoniazid and 3-hydroxy-N-(4-nitrophenyl)naphthalene-2-carboxamide expressed higher activity (MIC = 13.0 µmol/L) against M. kansasii than the standard isoniazid. Cytotoxicity assay of effective antimicrobial compounds was performed using the human monocytic leukemia THP-1 cell line. The PET-inhibiting activity expressed by IC50 value of the most active compound 3-hydroxy-N-(3-nitrophenyl)naphthalene-2-carboxamide was 16.9 μmol/L. The structure-activity relationships of all compounds are discussed.

Highlights

The increasing number of bacterial, mycobacterial and associated fungal infections underlines the importance of searching for new antimicrobial chemotherapeutics [1]
All the studied compounds were prepared according to Scheme 1
At first the carboxyl group was activated with phosphorus trichloride

Summary

Introduction

The increasing number of bacterial, mycobacterial and associated fungal infections underlines the importance of searching for new antimicrobial chemotherapeutics [1]. Tuberculosis and other mycobacterial diseases are common, and in many cases lethal, infectious illnesses caused by various strains of pathogenic mycobacteria. To lower risks and make manipulation in the laboratory easier, surrogate model pathogens for M. tuberculosis can be used in laboratory studies. M. marinum is very closely related to the M. tuberculosis; it is the cause of TB-like infections in poikilothermic organisms, especially frogs and fish. M. marinum is a good model for studying because of the lower risk for laboratory workers, genetic relatedness and similar pathology to human TB [2,3]. Because of M. tuberculosis, the pathogenic role of nontuberculous mycobacteria (NTM) in humans was overshadowed for a long time. M. kansasii, the most virulent of the NTM, causes nontuberculous mycobacterial lung infections which are very common nowadays and can be indistinguishable from tuberculosis [4].

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Results

Conclusion