Journal article
Solid-phase synthesis and biological evaluation of piperazine-based novel bacterial topoisomerase inhibitors
There is an emerging global need for new and more effective antibiotics against multi-resistant bacteria. This situation has led to massive industrial investigations on novel bacterial topoisomerase inhibitors (NBTIs) that target the vital bacterial enzymes DNA gyrase and topoisomerase IV. However, several of the NBTI compound classes have been associated with inhibition of the hERG potassium channel, an undesired cause of cardiac arrhythmia, which challenges medicinal chemistry efforts through lengthy synthetic routes.
We herein present a solid-phase strategy that rapidly facilitates the chemical synthesis of a promising new class of NBTIs. A proof-of-concept library was synthesized with the ability to modulate both hERG affinity and antibacterial activity through scaffold substitutions.
Language: | English |
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Year: | 2022 |
Pages: | 128499 |
ISSN: | 14643405 and 0960894x |
Types: | Journal article |
DOI: | 10.1016/j.bmcl.2021.128499 |
ORCIDs: | 0000-0002-1671-2155 , 0000-0002-9751-474X , 0000-0001-5004-8609 and Qvortrup, Katrine |
Antibiotics Bacterial Topoisomerase Inhibitors (NBTIs) SAR study Solid-Phase Synthesis hERG potassium channel
Anti-Bacterial Agents ERG protein, human Humans Methicillin-Resistant Staphylococcus aureus Microbial Sensitivity Tests Molecular Structure Piperazines Proof of Concept Study Quinolines Small Molecule Libraries Solid-Phase Synthesis Techniques Solid-phase synthesis Structure-Activity Relationship Topoisomerase II Inhibitors Transcriptional Regulator ERG