Antimicrobial and ADME properties of methoxylated, methylated and nitrated 2-hydroxynaphthalene-1 carboxanilides
Background and purpose: Many new compounds are being prepared to overcome the problem of increasing microbial resistance and the increasing number of infections. Experimental approach: This study includes a series of twenty-seven mono-, di- and trisubstituted 2-hydroxynaphthalene-1-carboxanilides d...
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International Association of Physical Chemists (IAPC)
2025-02-01
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| Series: | ADMET and DMPK |
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| Online Access: | https://pub.iapchem.org/ojs/index.php/admet/article/view/2642 |
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| author | Lucia Vrablova Tomas Gonec Tereza Kauerova Michal Oravec Izabela Jendrzejewska Peter Kollar Alois Cizek Josef Jampilek |
| author_facet | Lucia Vrablova Tomas Gonec Tereza Kauerova Michal Oravec Izabela Jendrzejewska Peter Kollar Alois Cizek Josef Jampilek |
| author_sort | Lucia Vrablova |
| collection | DOAJ |
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Background and purpose: Many new compounds are being prepared to overcome the problem of increasing microbial resistance and the increasing number of infections. Experimental approach: This study includes a series of twenty-seven mono-, di- and trisubstituted 2-hydroxynaphthalene-1-carboxanilides designed as multitarget agents. The compounds are substituted with methoxy, methyl, and nitro groups, as well as additionally with chlorine, bromine, and trifluoromethyl at various positions. All the compounds were evaluated for antibacterial activities against Gram-positive and Gram-negative bacteria and mycobacteria. Cytotoxicity on human cells was also tested. Key results: Three compounds showed activity comparable to clinically used drugs. N-(3,5-Dimethylphenyl)-2-hydroxynaphthalene-1-carboxamide (13) showed only anti¬sta¬phylococcal activity (minimum inhibitory concentration (MIC) = 54.9 µM); 2-hydroxy-N-[2-methyl-5-(tri¬fluoro¬methyl)phenyl]naphthalene-1-carboxamide (22) and 2-hydroxy-N-[4-nitro-3-(trifluoromethyl)phe¬nyl]na¬phtha¬lene-1-carboxamide (27) were active across the entire spectrum of tested bacteria/mycobacteria, both against the sensitive set and against resistant isolates (MICs range 0.3 to 92.6 µM). Compound 22 was even active against E. coli (MIC = 23.2 µM). The active agents showed no in vitro cytotoxicity up to a concentration of 30 μM. Conclusion: Compounds with trifluoromethyl in the meta-anilide position, experimental lipophilicity expressed as log k (logarithm of the capacity factor) in the range of 0.31 to 0.34 and calculated electron σ parameter for the anilide substituent higher than 0.59 were effective. The investigated compounds meet the definition of Michael acceptors. Based on ADME screening, the investigated compounds 13, 22 and 27 should have suitable physico¬chemical parameters for good bioavailability in the organism. Therefore, these are promising agents for further study.
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| format | Article |
| id | doaj-art-e1fc9b8901c5455f85f974c20dc01770 |
| institution | Kabale University |
| issn | 1848-7718 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | International Association of Physical Chemists (IAPC) |
| record_format | Article |
| series | ADMET and DMPK |
| spelling | doaj-art-e1fc9b8901c5455f85f974c20dc017702025-02-11T07:58:58ZengInternational Association of Physical Chemists (IAPC)ADMET and DMPK1848-77182025-02-0110.5599/admet.2642Antimicrobial and ADME properties of methoxylated, methylated and nitrated 2-hydroxynaphthalene-1 carboxanilidesLucia Vrablova0Tomas Gonec1Tereza Kauerova2Michal Oravec3Izabela Jendrzejewska4Peter Kollar5Alois Cizek6Josef Jampilek7Department of Analytical Chemistry, Faculty of Natural Sciences, Comenius University, Ilkovicova 6, 842 15 Bratislava, SlovakiaDepartment of Chemical Drugs, Faculty of Pharmacy, Masaryk University, Palackeho tr. 1946/1, 612 00 Brno, Czech RepublicDepartment of Pharmacology and Toxicology, Faculty of Pharmacy, Masaryk University, Palackeho tr. 1946/1, 612 00 Brno, Czech RepublicGlobal Change Research Institute CAS, Belidla 986/4a, 603 00 Brno, Czech RepublicInstitute of Chemistry, University of Silesia, Bankowa 12, 40007 Katowice, PolandDepartment of Pharmacology and Toxicology, Faculty of Pharmacy, Masaryk University, Palackeho tr. 1946/1, 612 00 Brno, Czech RepublicDepartment of Infectious Diseases and Microbiology, Faculty of Veterinary Medicine, University of Veterinary Sciences Brno, Palackeho tr. 1946/1, 612 42 Brno, Czech Republic Department of Chemical Biology, Faculty of Science, Palacky University Olomouc, Slechtitelu 27, 779 00 Olomouc, Czech Republic Background and purpose: Many new compounds are being prepared to overcome the problem of increasing microbial resistance and the increasing number of infections. Experimental approach: This study includes a series of twenty-seven mono-, di- and trisubstituted 2-hydroxynaphthalene-1-carboxanilides designed as multitarget agents. The compounds are substituted with methoxy, methyl, and nitro groups, as well as additionally with chlorine, bromine, and trifluoromethyl at various positions. All the compounds were evaluated for antibacterial activities against Gram-positive and Gram-negative bacteria and mycobacteria. Cytotoxicity on human cells was also tested. Key results: Three compounds showed activity comparable to clinically used drugs. N-(3,5-Dimethylphenyl)-2-hydroxynaphthalene-1-carboxamide (13) showed only anti¬sta¬phylococcal activity (minimum inhibitory concentration (MIC) = 54.9 µM); 2-hydroxy-N-[2-methyl-5-(tri¬fluoro¬methyl)phenyl]naphthalene-1-carboxamide (22) and 2-hydroxy-N-[4-nitro-3-(trifluoromethyl)phe¬nyl]na¬phtha¬lene-1-carboxamide (27) were active across the entire spectrum of tested bacteria/mycobacteria, both against the sensitive set and against resistant isolates (MICs range 0.3 to 92.6 µM). Compound 22 was even active against E. coli (MIC = 23.2 µM). The active agents showed no in vitro cytotoxicity up to a concentration of 30 μM. Conclusion: Compounds with trifluoromethyl in the meta-anilide position, experimental lipophilicity expressed as log k (logarithm of the capacity factor) in the range of 0.31 to 0.34 and calculated electron σ parameter for the anilide substituent higher than 0.59 were effective. The investigated compounds meet the definition of Michael acceptors. Based on ADME screening, the investigated compounds 13, 22 and 27 should have suitable physico¬chemical parameters for good bioavailability in the organism. Therefore, these are promising agents for further study. https://pub.iapchem.org/ojs/index.php/admet/article/view/2642lipophilicityantibacterial activityantimycobacterial activitycytotoxicity |
| spellingShingle | Lucia Vrablova Tomas Gonec Tereza Kauerova Michal Oravec Izabela Jendrzejewska Peter Kollar Alois Cizek Josef Jampilek Antimicrobial and ADME properties of methoxylated, methylated and nitrated 2-hydroxynaphthalene-1 carboxanilides ADMET and DMPK lipophilicity antibacterial activity antimycobacterial activity cytotoxicity |
| title | Antimicrobial and ADME properties of methoxylated, methylated and nitrated 2-hydroxynaphthalene-1 carboxanilides |
| title_full | Antimicrobial and ADME properties of methoxylated, methylated and nitrated 2-hydroxynaphthalene-1 carboxanilides |
| title_fullStr | Antimicrobial and ADME properties of methoxylated, methylated and nitrated 2-hydroxynaphthalene-1 carboxanilides |
| title_full_unstemmed | Antimicrobial and ADME properties of methoxylated, methylated and nitrated 2-hydroxynaphthalene-1 carboxanilides |
| title_short | Antimicrobial and ADME properties of methoxylated, methylated and nitrated 2-hydroxynaphthalene-1 carboxanilides |
| title_sort | antimicrobial and adme properties of methoxylated methylated and nitrated 2 hydroxynaphthalene 1 carboxanilides |
| topic | lipophilicity antibacterial activity antimycobacterial activity cytotoxicity |
| url | https://pub.iapchem.org/ojs/index.php/admet/article/view/2642 |
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