Design, synthesis and biological evaluation of novel DNA gyrase Inhibitors and their siderophore mimic conjugates

Andraž Lamut, Cristina D. Cruz, Žiga Skok, Michaela Barančoková, Nace Zidar, Anamarija Zega, Lucija Peterlin Mašič, Janez Ilaš, Päivi Tammela, Danijel Kikelj, Tihomir Tomašič

Tutkimustuotos: ArtikkelijulkaisuArtikkeliTieteellinenvertaisarvioitu

Abstrakti

Bacterial DNA gyrase is an important target for the development of novel antibacterial drugs, which are urgently needed because of high level of antibiotic resistance worldwide. We designed and synthesized new 4,5,6,7-tetrahydrobenzo[d]thiazole-based DNA gyrase B inhibitors and their conjugates with siderophore mimics, which were introduced to increase the uptake of inhibitors into the bacterial cytoplasm. The most potent conjugate 34 had an IC50 of 58 nM against Escherichia coli DNA gyrase and displayed MIC of 14 mu g/mL against E. coli.tolC strain. Only minor improvements in the antibacterial activities against wild-type E. coli in low-iron conditions were seen for DNA gyrase inhibitor - siderophore mimic conjugates.
Alkuperäiskielienglanti
Artikkeli103550
LehtiBioorganic Chemistry
Vuosikerta95
Sivumäärä13
ISSN0045-2068
DOI - pysyväislinkit
TilaJulkaistu - 2020
OKM-julkaisutyyppiA1 Alkuperäisartikkeli tieteellisessä aikakauslehdessä, vertaisarvioitu

Tieteenalat

  • 1182 Biokemia, solu- ja molekyylibiologia
  • 317 Farmasia

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