Original scientific paper

https://doi.org/10.2478/aiht-2021-72-3483

Characterisation of twelve newly synthesised N-(substituted phenyl)-2-chloroacetamides with QSAR analysis and antimicrobial activity tests

Aleksandra Bogdanović ; University of Belgrade Faculty of Technology and Metallurgy, Belgrade, Serbia
Anita Lazić ; University of Belgrade Faculty of Technology and Metallurgy, Innovation Centre, Belgrade, Serbia
Slavica Grujić ; University of Belgrade Faculty of Biology, Belgrade, Serbia
Ivica Dimkić orcid.org/0000-0002-0425-5938 ; University of Belgrade Faculty of Biology, Belgrade, Serbia
Slaviša Stanković ; University of Belgrade Faculty of Biology, Belgrade, Serbia
Slobodan Petrović ; University of Belgrade Faculty of Technology and Metallurgy, Belgrade, Serbia

Abstract

In this study we screened twelve newly synthesised N-(substituted phenyl)-2-chloroacetamides for antimicrobial potential relying on quantitative structure-activity relationship (QSAR) analysis based on the available cheminformatics prediction models (Molinspiration, SwissADME, PreADMET, and PkcSM) and verified it through standard antimicrobial testing against Escherichia coli, Staphylococcus aureus, methicillin-resistant S. aureus (MRSA), and Candida albicans. Our compounds met all the screening criteria of Lipinski’s rule of five (Ro5) as well as Veber’s and Egan’s methods for predicting biological activity. In antimicrobial activity tests, all chloroacetamides were effective against Gram-positive S. aureus and MRSA, less effective against the Gram-negative E. coli, and moderately effective against the yeast C. albicans. Our study confirmed that the biological activity of chloroacetamides varied with the position of substituents bound to the phenyl ring, which explains why some molecules were more effective against Gram-negative than Grampositive bacteria or C. albicans. Bearing the halogenated p-substituted phenyl ring, N-(4-chlorophenyl), N-(4-fluorophenyl), and N-(3-bromophenyl) chloroacetamides were among the most active thanks to high lipophilicity, which allows them to pass rapidly through the phospholipid bilayer of the cell membrane. They are the most promising compounds for further investigation, particularly against Gram-positive bacteria and pathogenic yeasts.

Keywords

N-substituted amides; antimicrobial potential; quantitative analysis of chemical structure and activity relationship

Hrčak ID:

253771

URI

https://hrcak.srce.hr/253771

Publication date:

16.3.2021.

Article data in other languages: croatian

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