@article{
author = "Kokot, Maja and Weiss, Matjaž and Zdovc, Irena and Šenerović, Lidija and Radakovic, Natasa and Anderluh, Marko and Minovski, Nikola and Hrast, Martina",
year = "2023",
abstract = "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.",
journal = "European Journal of Medicinal Chemistry, European Journal of Medicinal ChemistryEuropean Journal of Medicinal Chemistry",
title = "Amide containing NBTI antibacterials with reduced hERG inhibition, retained antimicrobial activity against gram-positive bacteria and in vivo efficacy",
pages = "115160",
volume = "250",
doi = "10.1016/j.ejmech.2023.115160"
}