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Increased antibacterial properties of indoline-derived phenolic Mannich bases

2021-04-20Journal article Restricted access
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dc.contributor.authorRimpiläinen, Tatu
dc.contributor.authorNunes, Alexandra
dc.contributor.authorCalado, Rita
dc.contributor.authorFernandes, Ana S.
dc.contributor.authorAndrade, Joana
dc.contributor.authorNtungwe, Epole
dc.contributor.authorSpengler, Gabriella
dc.contributor.authorSzemerédi, Nikoletta
dc.contributor.authorRodrigues, João
dc.contributor.authorGomes, João Paulo
dc.contributor.authorRijo, Patricia
dc.contributor.authorCandeias, Nuno R.
dc.date.accessioned2022-07-05T14:56:26Z
dc.date.available2022-07-05T14:56:26Z
dc.date.issued2021-04-20
dc.description.abstractThe search for antibacterial agents for the combat of nosocomial infections is a timely problem, as antibiotic-resistant bacteria continue to thrive. The effect of indoline substituents on the antibacterial properties of aminoalkylphenols was studied, leading to the development of a library of compounds with minimum inhibitory concentrations (MICs) as low as 1.18 μM. Two novel aminoalkylphenols were identified as particularly promising, after MIC and minimum bactericidal concentrations (MBC) determination against a panel of reference strain Gram-positive bacteria, and further confirmed against 40 clinical isolates (Staphylococcus aureus, Staphylococcus epidermidis, Enterococcus faecalis, Enterococcus faecium, and Listeria monocytogenes). The same two aminoalkylphenols displayed low toxicity against two in vivo models (Artemia salina brine shrimp and Saccharomyces cerevisiae). The in vitro cytotoxicity evaluation (on human keratinocytes and human embryonic lung fibroblast cell lines) of the same compounds was also carried out. They demonstrated a particularly toxic effect on the fibroblast cell lines, with IC50 in the 1.7-5.1 μM range, thus narrowing their clinical use. The desired increase in the antibacterial properties of the aminoalkylphenols, particularly indoline-derived phenolic Mannich bases, was reached by introducing an additional nitro group in the indolinyl substituent or by the replacement of a methyl by a bioisosteric trifluoromethyl substituent in the benzyl group introduced through use of boronic acids in the Petasis borono-Mannich reaction. Notably, the introduction of an additional nitro moiety did not confer added toxicity to the aminoalkylphenols.pt_PT
dc.description.abstractHighlights: - Indoline-derived phenol Mannich bases inhibited growth of some Gram-positive bacteria; - Aminoalkylphenols showed MICs as low as 0.59 μM against some clinical isolates; -Aminoalkylphenols were easily obtained through multicomponent Petasis reaction; - Antibacterial properties depend on the indoline substituents.pt_PT
dc.description.sponsorshipJane and Aatos Erkko Foundation, Academy of Finland (Decision 326487) and Fundaçao para a Ciência e Tecnologia (UIDB/50006/2020 and CEE-CINST/2018) are acknowledged for financial support.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationEur J Med Chem. 2021 Aug 5;220:113459. doi: 10.1016/j.ejmech.2021.113459. Epub 2021 Apr 20.pt_PT
dc.identifier.doi10.1016/j.ejmech.2021.113459pt_PT
dc.identifier.issn0223-5234
dc.identifier.urihttp://hdl.handle.net/10400.18/8058
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherElsevier/ Société de Chimie Thérapeutiquept_PT
dc.relationAssociated Laboratory for Green Chemistry - Clean Technologies and Processes
dc.relation.publisherversionhttps://www.sciencedirect.com/science/article/abs/pii/S0223523421003081?via%3Dihubpt_PT
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/pt_PT
dc.subjectAminoalkylphenolspt_PT
dc.subjectAntibacterialspt_PT
dc.subjectGram-positivept_PT
dc.subjectNosocomial infectionspt_PT
dc.subjectResistência aos Antimicrobianospt_PT
dc.subjectCuidados de Saúdept_PT
dc.titleIncreased antibacterial properties of indoline-derived phenolic Mannich basespt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.awardTitleAssociated Laboratory for Green Chemistry - Clean Technologies and Processes
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UIDB%2F50006%2F2020/PT
oaire.citation.startPage113459pt_PT
oaire.citation.titleEuropean Journal of Medicinal Chemistrypt_PT
oaire.citation.volume220pt_PT
oaire.fundingStream6817 - DCRRNI ID
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.nameFundação para a Ciência e a Tecnologia
rcaap.embargofctAcesso de acordo com política editorial da revista.pt_PT
rcaap.rightsembargoedAccesspt_PT
rcaap.typearticlept_PT
relation.isProjectOfPublicationeccce5f3-585c-46ef-9277-7db5962d45f7
relation.isProjectOfPublication.latestForDiscoveryeccce5f3-585c-46ef-9277-7db5962d45f7

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