Characterisation of twelve newly synthesised N-(substituted phenyl)-2-chloroacetamides with QSAR analysis and antimicrobial activity tests
2021
Authors
Bogdanović, AleksandraLazić, Anita
Grujic, Slavica
Dimkic, Ivica
Stankovic, Slavisa
Petrović, Slobodan
Article (Published version)
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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 molecu...les 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.
Keywords:
N-substituted amides / antimicrobial potential / quantitative analysis of chemical structure and activity relationshipSource:
Arhiv Za Higijenu Rada I Toksikologiju-Archives of Industrial Hygiene and Toxicology, 2021, 72, 1, 70-79Funding / projects:
- Ministry of Science, Technological Development and Innovation of the Republic of Serbia, institutional funding - 200135 (University of Belgrade, Faculty of Technology and Metallurgy) (RS-MESTD-inst-2020-200135)
- Ministry of Science, Technological Development and Innovation of the Republic of Serbia, institutional funding - 200178 (University of Belgrade, Faculty of Biology) (RS-MESTD-inst-2020-200178)
DOI: 10.2478/aiht-2021-72-3483
ISSN: 0004-1254
PubMed: 33787186
WoS: 000657362500009
Scopus: 2-s2.0-85103608918
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Tehnološko-metalurški fakultetTY - JOUR AU - Bogdanović, Aleksandra AU - Lazić, Anita AU - Grujic, Slavica AU - Dimkic, Ivica AU - Stankovic, Slavisa AU - Petrović, Slobodan PY - 2021 UR - http://TechnoRep.tmf.bg.ac.rs/handle/123456789/4912 AB - 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. T2 - Arhiv Za Higijenu Rada I Toksikologiju-Archives of Industrial Hygiene and Toxicology T1 - Characterisation of twelve newly synthesised N-(substituted phenyl)-2-chloroacetamides with QSAR analysis and antimicrobial activity tests EP - 79 IS - 1 SP - 70 VL - 72 DO - 10.2478/aiht-2021-72-3483 ER -
@article{ author = "Bogdanović, Aleksandra and Lazić, Anita and Grujic, Slavica and Dimkic, Ivica and Stankovic, Slavisa and Petrović, Slobodan", year = "2021", 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 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.", journal = "Arhiv Za Higijenu Rada I Toksikologiju-Archives of Industrial Hygiene and Toxicology", title = "Characterisation of twelve newly synthesised N-(substituted phenyl)-2-chloroacetamides with QSAR analysis and antimicrobial activity tests", pages = "79-70", number = "1", volume = "72", doi = "10.2478/aiht-2021-72-3483" }
Bogdanović, A., Lazić, A., Grujic, S., Dimkic, I., Stankovic, S.,& Petrović, S.. (2021). Characterisation of twelve newly synthesised N-(substituted phenyl)-2-chloroacetamides with QSAR analysis and antimicrobial activity tests. in Arhiv Za Higijenu Rada I Toksikologiju-Archives of Industrial Hygiene and Toxicology, 72(1), 70-79. https://doi.org/10.2478/aiht-2021-72-3483
Bogdanović A, Lazić A, Grujic S, Dimkic I, Stankovic S, Petrović S. Characterisation of twelve newly synthesised N-(substituted phenyl)-2-chloroacetamides with QSAR analysis and antimicrobial activity tests. in Arhiv Za Higijenu Rada I Toksikologiju-Archives of Industrial Hygiene and Toxicology. 2021;72(1):70-79. doi:10.2478/aiht-2021-72-3483 .
Bogdanović, Aleksandra, Lazić, Anita, Grujic, Slavica, Dimkic, Ivica, Stankovic, Slavisa, Petrović, Slobodan, "Characterisation of twelve newly synthesised N-(substituted phenyl)-2-chloroacetamides with QSAR analysis and antimicrobial activity tests" in Arhiv Za Higijenu Rada I Toksikologiju-Archives of Industrial Hygiene and Toxicology, 72, no. 1 (2021):70-79, https://doi.org/10.2478/aiht-2021-72-3483 . .