Solid-phase synthesis and biological evaluation of piperazine-based novel bacterial topoisomerase inhibitors
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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.
Originalsprog | Engelsk |
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Artikelnummer | 128499 |
Tidsskrift | Bioorganic and Medicinal Chemistry Letters |
Vol/bind | 57 |
ISSN | 0960-894X |
DOI | |
Status | Udgivet - 2022 |
Bibliografisk note
Funding Information:
The DSF Center for Antimicrobial Research, Danish Council for Independent Research (Technology and Production Sciences), and the Technical University of Denmark are gratefully acknowledged for financial support.
Publisher Copyright:
© 2021 The Authors
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