2. Academic Validation
  3. Design, synthesis and biological evaluation of novel DNA gyrase inhibitors and their siderophore mimic conjugates

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

  • Bioorg Chem. 2020 Jan;95:103550. doi: 10.1016/j.bioorg.2019.103550.
Andraž Lamut 1,  Cristina D Cruz 2,  Žiga Skok 1,  Michaela Barančoková 1,  Nace Zidar 1,  Anamarija Zega 1,  Lucija Peterlin Mašič 1,  Janez Ilaš 1,  Päivi Tammela 2,  Danijel Kikelj 1,  Tihomir Tomašič 3
Affiliations

Affiliations

  • 1 University of Ljubljana, Faculty of Pharmacy, Aškerčeva Cesta 7, 1000 Ljubljana, Slovenia.
  • 2 Drug Research Program, Division of Pharmaceutical Biosciences, Faculty of Pharmacy, University of Helsinki, P.O. Box 56 (Viikinkaari 5 E), FI-00014 Helsinki, Finland.
  • 3 University of Ljubljana, Faculty of Pharmacy, Aškerčeva Cesta 7, 1000 Ljubljana, Slovenia. Electronic address: [email protected].
PMID: 31911309 DOI: 10.1016/j.bioorg.2019.103550
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 µg/mL against E. coli ΔtolC 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.

Keywords

Antibiotics; Catechol; DNA gyrase; Inhibitors; Siderophore mimic.

Figures
Products