TY  - JOUR
AU  - Kokot, Maja
AU  - Weiss, Matjaž
AU  - Zdovc, Irena
AU  - Šenerović, Lidija
AU  - Radakovic, Natasa
AU  - Anderluh, Marko
AU  - Minovski, Nikola
AU  - Hrast, Martina
PY  - 2023
UR  - https://www.sciencedirect.com/science/article/pii/S0223523423000752
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1779
AB  - 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.
T2  - European Journal of Medicinal Chemistry
T2  - European Journal of Medicinal ChemistryEuropean Journal of Medicinal Chemistry
T1  - Amide containing NBTI antibacterials with reduced hERG inhibition, retained antimicrobial activity against gram-positive bacteria and in vivo efficacy
SP  - 115160
VL  - 250
DO  - 10.1016/j.ejmech.2023.115160
ER  - 

@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"
}

Kokot, M., Weiss, M., Zdovc, I., Šenerović, L., Radakovic, N., Anderluh, M., Minovski, N.,& Hrast, M.. (2023). Amide containing NBTI antibacterials with reduced hERG inhibition, retained antimicrobial activity against gram-positive bacteria and in vivo efficacy. in European Journal of Medicinal Chemistry, 250, 115160.
https://doi.org/10.1016/j.ejmech.2023.115160

Kokot M, Weiss M, Zdovc I, Šenerović L, Radakovic N, Anderluh M, Minovski N, Hrast M. Amide containing NBTI antibacterials with reduced hERG inhibition, retained antimicrobial activity against gram-positive bacteria and in vivo efficacy. in European Journal of Medicinal Chemistry. 2023;250:115160.
doi:10.1016/j.ejmech.2023.115160 .

Kokot, Maja, Weiss, Matjaž, Zdovc, Irena, Šenerović, Lidija, Radakovic, Natasa, Anderluh, Marko, Minovski, Nikola, Hrast, Martina, "Amide containing NBTI antibacterials with reduced hERG inhibition, retained antimicrobial activity against gram-positive bacteria and in vivo efficacy" in European Journal of Medicinal Chemistry, 250 (2023):115160,
https://doi.org/10.1016/j.ejmech.2023.115160 . .