Amide containing NBTI antibacterials with reduced hERG inhibition, retained antimicrobial activity against gram-positive bacteria and in vivo efficacy
| Autor: | Maja Kokot, Matjaž Weiss, Irena Zdovc, Lidija Senerovic, Natasa Radakovic, Marko Anderluh, Nikola Minovski, Martina Hrast |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2023 |
| Předmět: |
Pharmacology
DNA giraza topoizomeraza IV udc:615.28 Organic Chemistry DNA gyrase in vivo efficacy Farmacevtska kemija MRSA General Medicine DNA giraza topoizomeraza IV antibakterijska zdravila inhibicija učinkovitost in vivo učinkovitost in vivo NBTIs DNA gyrase Topoisomerase IV antibacterials MRSA hERG inhibition in vivo efficacy inhibicija bakterije hERG inhibition Bakterije antibakterijska zdravila Drug Discovery farmacevtska kemija NBTIs Topoisomerase IV antibacterials udc:615.2 |
| Zdroj: | European journal of medicinal chemistry, str. 1-13 : Ilustr., Vol. 250, 2023 COBISS-ID: 25429760 European journal of medicinal chemistry, vol. 115160, no. 250, pp. 1-13, 2023. |
| ISSN: | 0223-5234 |
| Popis: | Novel bacterial topoisomerase inhibitors (NBTIs) are new promising antimicrobials for the treatment of multidrug-resistant bacterial infections. In recent years, many new NBTIs have been discovered, however most of them struggle with the same issue - the balance between antibacterial activity and hERG-related toxicity. We started a new campaign by optimizing the previous series of NBTIs, followed by the design and synthesis of a new, amide-containing focused NBTI library to reduce hERG inhibition and maintain antibacterial activity against Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA). This optimization strategy yielded the lead compound 12 that exhibits potent antibacterial activity against Gram-positive bacteria, reduced hERG inhibition, no cardiotoxicity in zebrafish model, and a favorable in vivo efficacy in a neutropenic murine thigh infection model of MRSA infection. Št. članka: 115160. Bibliografija: str. 12-13. Abstract. ARRS ARRS Young researcher’s program Young researcher’s program |
| Databáze: | OpenAIRE |
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