Insight into antistaphylococcal effect of chlorinated 1-hydroxynaphthalene-2-carboxanilides
Lucia Vrablova1, Tomas Gonec2, Petra Majerova3
1Department of Analytical Chemistry, Faculty of Natural Sciences, Comenius University, Ilkovicova 6, 842 15 Bratislava, Slovakia.
Background And Purpose:
New compounds and innovative therapeutic approaches are trying to prevent antimicrobial resistance, which has become a global health challenge.
Experimental Approach:
This study includes a series of twelve mono-, di- and trichlorinated 1-hydroxynaphthalene-2-carboxanilides designed as multitarget agents. All compounds were evaluated for their antistaphylococcal activity. Furthermore, MTT assay and chemoproteomic analysis of selected compounds were performed. Cytotoxicity in human cells was also tested.
Key Results:
N-(3,5-Dichlorophenyl)-1-hydroxynaphthalene-2-carboxamide (10) demonstrated activity comparable to or higher than clinically used drugs, with minimum inhibitory concentrations (MICs) of 0.37 μM. The compound was equally effective against clinical isolates of methicillin-resistant S. aureus. On the other hand, compound 10 showed 96 % inhibition of S. aureus respiration only at a concentration of 16× MIC. Chemoproteomic analysis revealed that the effect of agent 10 on staphylococci resulted in the downregulation of four proteins. This compound expressed no in vitro cytotoxicity up to a concentration of 30 μM.
Conclusion:
From the set of tested mono-, di- and trisubstituted derivatives, it is evident that the position of chlorine atoms is decisive for significant antistaphylococcal activity. Inhibition of energy metabolism does not appear to be one of the main mechanisms of action of compound 10; on the contrary, the antibacterial effect may likely be contributed by downregulation of proteins (especially ATP-dependent protease ATPase subunit HslU) involved in processes essential for bacterial survival and growth, such as protein, nucleotide/nucleic acid synthesis and efficient protein repair/degradation.
More Related Videos
07:12Cercosporin-Photocatalyzed [4+1]- and [4+2]-Annulations of Azoalkenes Under Mild Conditions
Published on: July 17, 2020
12:07Microwave-assisted Intramolecular Dehydrogenative Diels-Alder Reactions for the Synthesis of Functionalized Naphthalenes/Solvatochromic Dyes
Published on: April 1, 2013
Related Concept Videos
Aryldiazonium Salts to Azo Dyes: Diazo Coupling
Physical Properties of Amines
Local Anesthetics: Adverse Effects
Once absorbed into the systemic circulation, local anesthetics can affect the organs that depend on the functioning of sodium...
Aromatic Hydrocarbon Anions: Structural Overview
Due to the absence of continuous...
Nucleophilic Aromatic Substitution: Elimination–Addition
Diazonium Group Substitution: –OH and –H
