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Development of Dicationic Bisguanidine-Arylfuran Derivatives as Potent Agents against Gram-Negative Bacteria.

Bourgard, Catarina, 1985 (author)
Gothenburg University,Göteborgs universitet,Institutionen för kemi och molekylärbiologi,CARe - Centrum för antibiotikaresistensforskning,Department of Chemistry and Molecular Biology,Centre for antibiotic resistance research, CARe
Rodríguez-Hernández, Diego (author)
Gothenburg University,Göteborgs universitet,Institutionen för kemi och molekylärbiologi,Department of Chemistry and Molecular Biology
Rudenko, Anastasia (author)
Gothenburg University,Göteborgs universitet,CARe - Centrum för antibiotikaresistensforskning,Institutionen för kemi och molekylärbiologi,Centre for antibiotic resistance research, CARe,Department of Chemistry and Molecular Biology
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Rutgersson, Carolin, 1983 (author)
Gothenburg University,Göteborgs universitet,CARe - Centrum för antibiotikaresistensforskning,Institutionen för biomedicin, avdelningen för infektionssjukdomar,Centre for antibiotic resistance research, CARe,Institute of Biomedicine, Department of Infectious Medicine
Palm, Martin (author)
Gothenburg University,Göteborgs universitet,Institutionen för kemi och molekylärbiologi,CARe - Centrum för antibiotikaresistensforskning,Department of Chemistry and Molecular Biology,Centre for antibiotic resistance research, CARe
Larsson, D. G. Joakim, 1969 (author)
Gothenburg University,Göteborgs universitet,Institutionen för biomedicin,CARe - Centrum för antibiotikaresistensforskning,Institute of Biomedicine,Centre for antibiotic resistance research, CARe
Farewell, Anne, 1961 (author)
Gothenburg University,Göteborgs universitet,CARe - Centrum för antibiotikaresistensforskning,Institutionen för kemi och molekylärbiologi,Centre for antibiotic resistance research, CARe,Department of Chemistry and Molecular Biology
Grøtli, Morten, 1966 (author)
Gothenburg University,Göteborgs universitet,Institutionen för kemi och molekylärbiologi,Department of Chemistry and Molecular Biology
Sunnerhagen, Per, 1959 (author)
Gothenburg University,Göteborgs universitet,CARe - Centrum för antibiotikaresistensforskning,Institutionen för kemi och molekylärbiologi,Centre for antibiotic resistance research, CARe,Department of Chemistry and Molecular Biology
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 (creator_code:org_t)
2022-08-17
2022
English.
In: Antibiotics. - : MDPI AG. - 2079-6382. ; 11:8
  • Journal article (peer-reviewed)
Abstract Subject headings
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  • Antibiotic resistance among bacteria is a growing global challenge. A major reason for this is the limited progress in developing new classes of antibiotics active against Gram-negative bacteria. Here, we investigate the antibacterial activity of a dicationic bisguanidine-arylfuran, originally developed as an antitrypanosomal agent, and new derivatives thereof. The compounds showed good activity (EC50 2-20 µM) against antibiotic-resistant isolates of the Gram-negative members of the ESKAPE group (Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Enterobacter spp.) and Escherichia coli with different antibiotic susceptibility patterns, including ESBL isolates. Cytotoxicity was moderate, and several of the new derivatives were less cytotoxic than the lead molecule, offering better selectivity indices (40-80 for several ESKAPE isolates). The molecular mechanism for the antibacterial activity of these molecules is unknown, but sensitivity profiling against human ESKAPE isolates and E. coli collections with known susceptibility patterns against established antibiotics indicates that it is distinct from lactam and quinolone antibiotics.

Subject headings

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Mikrobiologi inom det medicinska området (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Microbiology in the medical area (hsv//eng)
MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Läkemedelskemi (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Medicinal Chemistry (hsv//eng)

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