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

Research output: Contribution to journalArticleScientificpeer-review

Abstract

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.
Original languageEnglish
Article number103550
JournalBioorganic Chemistry
Volume95
Number of pages13
ISSN0045-2068
DOIs
Publication statusPublished - 2020
MoE publication typeA1 Journal article-refereed

Fields of Science

  • 1182 Biochemistry, cell and molecular biology
  • Antibiotics
  • Catechol
  • DNA gyrase
  • Inhibitors
  • Siderophore mimic
  • RESISTANCE
  • DISCOVERY
  • 317 Pharmacy

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