دورية أكاديمية
Repurposing anti-inflammatory drugs for fighting planktonic and biofilm growth. New carbazole derivatives based on the NSAID carprofen: synthesis, in silico and in vitro bioevaluation
| العنوان: | Repurposing anti-inflammatory drugs for fighting planktonic and biofilm growth. New carbazole derivatives based on the NSAID carprofen: synthesis, in silico and in vitro bioevaluation |
|---|---|
| المؤلفون: | Florea Dumitrascu, Mino R. Caira, Speranta Avram, Catalin Buiu, Ana Maria Udrea, Ilinca Margareta Vlad, Irina Zarafu, Petre Ioniță, Diana Camelia Nuță, Marcela Popa, Mariana-Carmen Chifiriuc, Carmen Limban |
| المصدر: | Frontiers in Cellular and Infection Microbiology, Vol 13 (2023) |
| بيانات النشر: | Frontiers Media S.A., 2023. |
| سنة النشر: | 2023 |
| المجموعة: | LCC:Microbiology |
| مصطلحات موضوعية: | carprofen, antibacterial, antibiofilm, ESKAPE pathogens, new carbazole derivatives, Microbiology, QR1-502 |
| الوصف: | IntroductionOne of the promising leads for the rapid discovery of alternative antimicrobial agents is to repurpose other drugs, such as nonsteroidal anti-inflammatory agents (NSAIDs) for fighting bacterial infections and antimicrobial resistance.MethodsA series of new carbazole derivatives based on the readily available anti-inflammatory drug carprofen has been obtained by nitration, halogenation and N-alkylation of carprofen and its esters. The structures of these carbazole compounds were assigned by NMR and IR spectroscopy. Regioselective electrophilic substitution by nitration and halogenation at the carbazole ring was assigned from H NMR spectra. The single crystal X-ray structures of two representative derivatives obtained by dibromination of carprofen, were also determined. The total antioxidant capacity (TAC) was measured using the DPPH method. The antimicrobial activity assay was performed using quantitative methods, allowing establishment of the minimal inhibitory/bactericidal/biofilm eradication concentrations (MIC/MBC/MBEC) on Gram-positive (Staphylococcus aureus, Enterococcus faecalis) and Gram-negative (Escherichia coli, Pseudomonas aeruginosa) strains. Computational assays have been performed to assess the drug- and lead-likeness, pharmacokinetics (ADME-Tox) and pharmacogenomics profiles.Results and discussionThe crystal X-ray structures of 3,8-dibromocarprofen and its methyl ester have revealed significant differences in their supramolecular assemblies. The most active antioxidant compound was 1i, bearing one chlorine and two bromine atoms, as well as the CO2Me group. Among the tested derivatives, 1h bearing one chlorine and two bromine atoms has exhibited the widest antibacterial spectrum and the most intensive inhibitory activity, especially against the Gram-positive strains, in planktonic and biofilm growth state. The compounds 1a (bearing one chlorine, one NO2 and one CO2Me group) and 1i (bearing one chlorine, two bromine atoms and a CO2Me group) exhibited the best antibiofilm activity in the case of the P. aeruginosa strain. Moreover, these compounds comply with the drug-likeness rules, have good oral bioavailability and are not carcinogenic or mutagenic. The results demonstrate that these new carbazole derivatives have a molecular profile which deserves to be explored further for the development of novel antibacterial and antibiofilm agents. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 2235-2988 |
| العلاقة: | https://www.frontiersin.org/articles/10.3389/fcimb.2023.1181516/fullTest; https://doaj.org/toc/2235-2988Test |
| DOI: | 10.3389/fcimb.2023.1181516 |
| الوصول الحر: | https://doaj.org/article/32fc50fa862e442ea44e4b46ea347e41Test |
| رقم الانضمام: | edsdoj.32fc50fa862e442ea44e4b46ea347e41 |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | ResultId |
1 |
|---|---|
| Header |
edsdoj Directory of Open Access Journals edsdoj.32fc50fa862e442ea44e4b46ea347e41 1007 3 Academic Journal academicJournal 1006.73883056641 |
| PLink |
https://search.ebscohost.com/login.aspx?direct=true&site=eds-live&scope=site&db=edsdoj&AN=edsdoj.32fc50fa862e442ea44e4b46ea347e41&custid=s6537998&authtype=sso |
| FullText |
Array
(
[Availability] => 0
)
Array ( [0] => Array ( [Url] => https://doaj.org/article/32fc50fa862e442ea44e4b46ea347e41 [Name] => EDS - DOAJ [Category] => fullText [Text] => View record in DOAJ [MouseOverText] => View record in DOAJ ) [1] => Array ( [Url] => https://resolver.ebscohost.com/openurl?custid=s6537998&groupid=main&authtype=ip,guest&sid=EBSCO:edsdoj&genre=article&issn=22352988&ISBN=&volume=13&issue=&date=20230801&spage=&pages=&title=Frontiers in Cellular and Infection Microbiology&atitle=Repurposing%20anti-inflammatory%20drugs%20for%20fighting%20planktonic%20and%20biofilm%20growth.%20New%20carbazole%20derivatives%20based%20on%20the%20NSAID%20carprofen%3A%20synthesis%2C%20in%20silico%20and%20in%20vitro%20bioevaluation&id=DOI:10.3389/fcimb.2023.1181516 [Name] => Full Text Finder (s6537998api) [Category] => fullText [Text] => Full Text Finder [Icon] => https://imageserver.ebscohost.com/branding/images/FTF.gif [MouseOverText] => Full Text Finder ) ) |
| Items |
Array
(
[Name] => Title
[Label] => Title
[Group] => Ti
[Data] => Repurposing anti-inflammatory drugs for fighting planktonic and biofilm growth. New carbazole derivatives based on the NSAID carprofen: synthesis, in silico and in vitro bioevaluation
)
Array ( [Name] => Author [Label] => Authors [Group] => Au [Data] => <searchLink fieldCode="AR" term="%22Florea+Dumitrascu%22">Florea Dumitrascu</searchLink><br /><searchLink fieldCode="AR" term="%22Mino+R%2E+Caira%22">Mino R. Caira</searchLink><br /><searchLink fieldCode="AR" term="%22Speranta+Avram%22">Speranta Avram</searchLink><br /><searchLink fieldCode="AR" term="%22Catalin+Buiu%22">Catalin Buiu</searchLink><br /><searchLink fieldCode="AR" term="%22Ana+Maria+Udrea%22">Ana Maria Udrea</searchLink><br /><searchLink fieldCode="AR" term="%22Ilinca+Margareta+Vlad%22">Ilinca Margareta Vlad</searchLink><br /><searchLink fieldCode="AR" term="%22Irina+Zarafu%22">Irina Zarafu</searchLink><br /><searchLink fieldCode="AR" term="%22Petre+Ioniță%22">Petre Ioniță</searchLink><br /><searchLink fieldCode="AR" term="%22Diana+Camelia+Nuță%22">Diana Camelia Nuță</searchLink><br /><searchLink fieldCode="AR" term="%22Marcela+Popa%22">Marcela Popa</searchLink><br /><searchLink fieldCode="AR" term="%22Mariana-Carmen+Chifiriuc%22">Mariana-Carmen Chifiriuc</searchLink><br /><searchLink fieldCode="AR" term="%22Carmen+Limban%22">Carmen Limban</searchLink> ) Array ( [Name] => TitleSource [Label] => Source [Group] => Src [Data] => Frontiers in Cellular and Infection Microbiology, Vol 13 (2023) ) Array ( [Name] => Publisher [Label] => Publisher Information [Group] => PubInfo [Data] => Frontiers Media S.A., 2023. ) Array ( [Name] => DatePubCY [Label] => Publication Year [Group] => Date [Data] => 2023 ) Array ( [Name] => Subset [Label] => Collection [Group] => HoldingsInfo [Data] => LCC:Microbiology ) Array ( [Name] => Subject [Label] => Subject Terms [Group] => Su [Data] => <searchLink fieldCode="DE" term="%22carprofen%22">carprofen</searchLink><br /><searchLink fieldCode="DE" term="%22antibacterial%22">antibacterial</searchLink><br /><searchLink fieldCode="DE" term="%22antibiofilm%22">antibiofilm</searchLink><br /><searchLink fieldCode="DE" term="%22ESKAPE+pathogens%22">ESKAPE pathogens</searchLink><br /><searchLink fieldCode="DE" term="%22new+carbazole+derivatives%22">new carbazole derivatives</searchLink><br /><searchLink fieldCode="DE" term="%22Microbiology%22">Microbiology</searchLink><br /><searchLink fieldCode="DE" term="%22QR1-502%22">QR1-502</searchLink> ) Array ( [Name] => Abstract [Label] => Description [Group] => Ab [Data] => IntroductionOne of the promising leads for the rapid discovery of alternative antimicrobial agents is to repurpose other drugs, such as nonsteroidal anti-inflammatory agents (NSAIDs) for fighting bacterial infections and antimicrobial resistance.MethodsA series of new carbazole derivatives based on the readily available anti-inflammatory drug carprofen has been obtained by nitration, halogenation and N-alkylation of carprofen and its esters. The structures of these carbazole compounds were assigned by NMR and IR spectroscopy. Regioselective electrophilic substitution by nitration and halogenation at the carbazole ring was assigned from H NMR spectra. The single crystal X-ray structures of two representative derivatives obtained by dibromination of carprofen, were also determined. The total antioxidant capacity (TAC) was measured using the DPPH method. The antimicrobial activity assay was performed using quantitative methods, allowing establishment of the minimal inhibitory/bactericidal/biofilm eradication concentrations (MIC/MBC/MBEC) on Gram-positive (Staphylococcus aureus, Enterococcus faecalis) and Gram-negative (Escherichia coli, Pseudomonas aeruginosa) strains. Computational assays have been performed to assess the drug- and lead-likeness, pharmacokinetics (ADME-Tox) and pharmacogenomics profiles.Results and discussionThe crystal X-ray structures of 3,8-dibromocarprofen and its methyl ester have revealed significant differences in their supramolecular assemblies. The most active antioxidant compound was 1i, bearing one chlorine and two bromine atoms, as well as the CO2Me group. Among the tested derivatives, 1h bearing one chlorine and two bromine atoms has exhibited the widest antibacterial spectrum and the most intensive inhibitory activity, especially against the Gram-positive strains, in planktonic and biofilm growth state. The compounds 1a (bearing one chlorine, one NO2 and one CO2Me group) and 1i (bearing one chlorine, two bromine atoms and a CO2Me group) exhibited the best antibiofilm activity in the case of the P. aeruginosa strain. Moreover, these compounds comply with the drug-likeness rules, have good oral bioavailability and are not carcinogenic or mutagenic. The results demonstrate that these new carbazole derivatives have a molecular profile which deserves to be explored further for the development of novel antibacterial and antibiofilm agents. ) Array ( [Name] => TypeDocument [Label] => Document Type [Group] => TypDoc [Data] => article ) Array ( [Name] => Format [Label] => File Description [Group] => SrcInfo [Data] => electronic resource ) Array ( [Name] => Language [Label] => Language [Group] => Lang [Data] => English ) Array ( [Name] => ISSN [Label] => ISSN [Group] => ISSN [Data] => 2235-2988 ) Array ( [Name] => NoteTitleSource [Label] => Relation [Group] => SrcInfo [Data] => https://www.frontiersin.org/articles/10.3389/fcimb.2023.1181516/full; https://doaj.org/toc/2235-2988 ) Array ( [Name] => DOI [Label] => DOI [Group] => ID [Data] => 10.3389/fcimb.2023.1181516 ) Array ( [Name] => URL [Label] => Access URL [Group] => URL [Data] => <link linkTarget="URL" linkTerm="https://doaj.org/article/32fc50fa862e442ea44e4b46ea347e41" linkWindow="_blank">https://doaj.org/article/32fc50fa862e442ea44e4b46ea347e41</link> ) Array ( [Name] => AN [Label] => Accession Number [Group] => ID [Data] => edsdoj.32fc50fa862e442ea44e4b46ea347e41 ) |
| RecordInfo |
Array
(
[BibEntity] => Array
(
[Identifiers] => Array
(
[0] => Array
(
[Type] => doi
[Value] => 10.3389/fcimb.2023.1181516
)
)
[Languages] => Array
(
[0] => Array
(
[Text] => English
)
)
[Subjects] => Array
(
[0] => Array
(
[SubjectFull] => carprofen
[Type] => general
)
[1] => Array
(
[SubjectFull] => antibacterial
[Type] => general
)
[2] => Array
(
[SubjectFull] => antibiofilm
[Type] => general
)
[3] => Array
(
[SubjectFull] => ESKAPE pathogens
[Type] => general
)
[4] => Array
(
[SubjectFull] => new carbazole derivatives
[Type] => general
)
[5] => Array
(
[SubjectFull] => Microbiology
[Type] => general
)
[6] => Array
(
[SubjectFull] => QR1-502
[Type] => general
)
)
[Titles] => Array
(
[0] => Array
(
[TitleFull] => Repurposing anti-inflammatory drugs for fighting planktonic and biofilm growth. New carbazole derivatives based on the NSAID carprofen: synthesis, in silico and in vitro bioevaluation
[Type] => main
)
)
)
[BibRelationships] => Array
(
[HasContributorRelationships] => Array
(
[0] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => Florea Dumitrascu
)
)
)
[1] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => Mino R. Caira
)
)
)
[2] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => Speranta Avram
)
)
)
[3] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => Catalin Buiu
)
)
)
[4] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => Ana Maria Udrea
)
)
)
[5] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => Ilinca Margareta Vlad
)
)
)
[6] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => Irina Zarafu
)
)
)
[7] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => Petre Ioniță
)
)
)
[8] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => Diana Camelia Nuță
)
)
)
[9] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => Marcela Popa
)
)
)
[10] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => Mariana-Carmen Chifiriuc
)
)
)
[11] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => Carmen Limban
)
)
)
)
[IsPartOfRelationships] => Array
(
[0] => Array
(
[BibEntity] => Array
(
[Dates] => Array
(
[0] => Array
(
[D] => 01
[M] => 08
[Type] => published
[Y] => 2023
)
)
[Identifiers] => Array
(
[0] => Array
(
[Type] => issn-print
[Value] => 22352988
)
)
[Numbering] => Array
(
[0] => Array
(
[Type] => volume
[Value] => 13
)
)
[Titles] => Array
(
[0] => Array
(
[TitleFull] => Frontiers in Cellular and Infection Microbiology
[Type] => main
)
)
)
)
)
)
)
|
| IllustrationInfo |