Characterisation of twelve newly synthesised N-(substituted phenyl)-2-chloroacetamides with QSAR analysis and antimicrobial activity tests
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) a...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Sciendo
2021-03-01
|
| Series: | Arhiv za Higijenu Rada i Toksikologiju |
| Subjects: | |
| Online Access: | https://doi.org/10.2478/aiht-2021-72-3483 |
| _version_ | 1811272314825736192 |
|---|---|
| author | Bogdanović Aleksandra Lazić Anita Grujić Slavica Dimkić Ivica Stanković Slaviša Petrović Slobodan |
| author_facet | Bogdanović Aleksandra Lazić Anita Grujić Slavica Dimkić Ivica Stanković Slaviša Petrović Slobodan |
| author_sort | Bogdanović Aleksandra |
| collection | DOAJ |
| description | 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 Gram-positive 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. |
| first_indexed | 2024-04-12T22:38:01Z |
| format | Article |
| id | doaj.art-3edc8afd3c214dabb97ba767d60f94dd |
| institution | Directory Open Access Journal |
| issn | 1848-6312 |
| language | English |
| last_indexed | 2024-04-12T22:38:01Z |
| publishDate | 2021-03-01 |
| publisher | Sciendo |
| record_format | Article |
| series | Arhiv za Higijenu Rada i Toksikologiju |
| spelling | doaj.art-3edc8afd3c214dabb97ba767d60f94dd2022-12-22T03:13:48ZengSciendoArhiv za Higijenu Rada i Toksikologiju1848-63122021-03-01721707910.2478/aiht-2021-72-3483Characterisation of twelve newly synthesised N-(substituted phenyl)-2-chloroacetamides with QSAR analysis and antimicrobial activity testsBogdanović Aleksandra0Lazić Anita1Grujić Slavica2Dimkić Ivica3Stanković Slaviša4Petrović Slobodan5University of Belgrade Faculty of Technology and Metallurgy, Belgrade, SerbiaUniversity of Belgrade Faculty of Technology and Metallurgy, Innovation Centre, Belgrade, SerbiaUniversity of Belgrade Faculty of Biology, Belgrade, SerbiaUniversity of Belgrade Faculty of Biology, Belgrade, SerbiaUniversity of Belgrade Faculty of Biology, Belgrade, SerbiaUniversity of Belgrade Faculty of Technology and Metallurgy, Belgrade, SerbiaIn 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 Gram-positive 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.https://doi.org/10.2478/aiht-2021-72-3483n-substituted amidesantimicrobial potentialquantitative analysis of chemical structure and activity relationshipn-supstituirani amidiantimikrobni potencijalkvantitativna analiza kemijske strukture i aktivnosti spojeva |
| spellingShingle | Bogdanović Aleksandra Lazić Anita Grujić Slavica Dimkić Ivica Stanković Slaviša Petrović Slobodan Characterisation of twelve newly synthesised N-(substituted phenyl)-2-chloroacetamides with QSAR analysis and antimicrobial activity tests Arhiv za Higijenu Rada i Toksikologiju n-substituted amides antimicrobial potential quantitative analysis of chemical structure and activity relationship n-supstituirani amidi antimikrobni potencijal kvantitativna analiza kemijske strukture i aktivnosti spojeva |
| title | Characterisation of twelve newly synthesised N-(substituted phenyl)-2-chloroacetamides with QSAR analysis and antimicrobial activity tests |
| title_full | Characterisation of twelve newly synthesised N-(substituted phenyl)-2-chloroacetamides with QSAR analysis and antimicrobial activity tests |
| title_fullStr | Characterisation of twelve newly synthesised N-(substituted phenyl)-2-chloroacetamides with QSAR analysis and antimicrobial activity tests |
| title_full_unstemmed | Characterisation of twelve newly synthesised N-(substituted phenyl)-2-chloroacetamides with QSAR analysis and antimicrobial activity tests |
| title_short | Characterisation of twelve newly synthesised N-(substituted phenyl)-2-chloroacetamides with QSAR analysis and antimicrobial activity tests |
| title_sort | characterisation of twelve newly synthesised n substituted phenyl 2 chloroacetamides with qsar analysis and antimicrobial activity tests |
| topic | n-substituted amides antimicrobial potential quantitative analysis of chemical structure and activity relationship n-supstituirani amidi antimikrobni potencijal kvantitativna analiza kemijske strukture i aktivnosti spojeva |
| url | https://doi.org/10.2478/aiht-2021-72-3483 |
| work_keys_str_mv | AT bogdanovicaleksandra characterisationoftwelvenewlysynthesisednsubstitutedphenyl2chloroacetamideswithqsaranalysisandantimicrobialactivitytests AT lazicanita characterisationoftwelvenewlysynthesisednsubstitutedphenyl2chloroacetamideswithqsaranalysisandantimicrobialactivitytests AT grujicslavica characterisationoftwelvenewlysynthesisednsubstitutedphenyl2chloroacetamideswithqsaranalysisandantimicrobialactivitytests AT dimkicivica characterisationoftwelvenewlysynthesisednsubstitutedphenyl2chloroacetamideswithqsaranalysisandantimicrobialactivitytests AT stankovicslavisa characterisationoftwelvenewlysynthesisednsubstitutedphenyl2chloroacetamideswithqsaranalysisandantimicrobialactivitytests AT petrovicslobodan characterisationoftwelvenewlysynthesisednsubstitutedphenyl2chloroacetamideswithqsaranalysisandantimicrobialactivitytests |