20.500.12556/RUL-134779 Hybrid inhibitors of DNA gyrase A and B design, synthesis and evaluation The discovery of multi-targeting ligands of bacterial enzymes is an important strategy to combat rapidly spreading antimicrobial resistance. Bacterial DNA gyrase and topoisomerase IV are validated targets for the development of antibiotics. They can be inhibited at their catalytic sites or at their ATP binding sites. Here we present the design of new hybrids between the catalytic inhibitor ciprofloxacin and ATP-competitive inhibitors that show low nanomolar inhibition of DNA gyrase and antibacterial activity against Gram-negative pathogens. The most potent hybrid 3a has MICs of 0.5 µg/mL against Klebsiella pneumoniae, 4 µg/mL against Enterobacter cloacae, and 2 µg/mL against Escherichia coli. In addition, inhibition of mutant E. coli strains shows that these hybrid inhibitors interact with both subunits of DNA gyrase (GyrA, GyrB), and that binding to both of these sites contributes to their antibacterial activity. antibacterial ciprofloxacin DNA gyrase dual inhibitor hybrid DNK giraze ciprofloksacin zaviralci hibridi bakterijska rezistenca farmacevtska kemija true false true Angleški jezik Slovenski jezik Članek v reviji 2022-02-01 13:52:38 2022-02-01 13:52:41 2022-09-14 04:09:52 0000-00-00 00:00:00 2021 0 0 17 str. iss. 1, art. 6 Vol. 13 2021 0000-00-00 Zaloznikova Objavljeno NiDoloceno 0000-00-00 0000-00-00 0000-00-00 615.4:54:615.015.8 1999-4923 10.3390/pharmaceutics13010006 44007939 RAZ_Durcik_Martina_2021.pdf RAZ_Durcik_Martina_2021.pdf 1 55614DE5A88BB31AD352E271FDB12DC6 d9cf370e6e61f81c9261abb7cb3b695d4ffb86224b3fed0eea5af91856f39d7f d9672bbc-835d-11ec-abdb-00155dcfd717 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=153417 https://www.mdpi.com/1999-4923/13/1/6 1 a1831e2a-835d-11ec-abdb-00155dcfd717 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=153416 Fakulteta za farmacijo 0 0 0