20.500.12556/RUL-141453 Structurally optimized potent dual-targeting NBTI antibacterials with an enhanced bifurcated halogen-bonding propensity We designed and synthesized an optimized library of novel bacterial topoisomerase inhibitors with p-halogenated phenyl right-hand side fragments and significantly enhanced and balanced dual-targeted DNA gyrase and topoisomerase IV activities of Staphylococcus aureus and Escherichia coli. By increasing the electron-withdrawing properties of the p-halogenated phenyl right-hand side fragment and maintaining a similar lipophilicity and size, an increased potency was achieved, indicating that the antibacterial activities of this series of novel bacterial topoisomerase inhibitors against all target enzymes are determined by halogen-bonding rather than van der Waals interactions. They show nanomolar enzyme inhibitory and whole-cell antibacterial activities against S. aureus and methicillin-resistant S. aureus (MRSA) strains. However, due to the relatively high substrate specificity for the bacterial efflux pumps, they tend to be less potent against E. coli and other Gram-negative pathogens. NBTIs DNA gyrase topoisomerase IV bifurcated halogen bonds dual targeting true false true Angleški jezik Angleški jezik Članek v reviji 2022-09-29 12:56:15 2022-09-29 12:56:16 2022-09-30 04:10:59 0000-00-00 00:00:00 2021 0 0 Str. 1478-1485 iss. 9 Vol. 12 2021 0000-00-00 Zaloznikova Objavljeno NiDoloceno 0000-00-00 0000-00-00 0000-00-00 615.4:54:579 1948-5875 10.1021/acsmedchemlett.1c00345 73185027 acsmedchemlett.1c00345.pdf acsmedchemlett.1c00345.pdf 1 51A524CEF864D7B1E316043F423040F5 4de33f1b6fe6c21c83613e13498d758c740ddf30a92d7df7da2add046daf6d2d b3dbfc78-3fe5-11ed-9c94-00155dcfd717 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=162519 https://pubs.acs.org/doi/10.1021/acsmedchemlett.1c00345 1 55004168-3fe5-11ed-9c94-00155dcfd717 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=162517 Fakulteta za farmacijo 0 0 0