A Fine-Tuned Lipophilicity/Hydrophilicity Ratio Governs Antibacterial Potency and Selectivity of Bifurcated Halogen Bond-Forming NBTIs
| Autor: | Irena Zdovc, Matjaž Weiss, Marko Anderluh, Anja Kolarič, Simon Žakelj, Martina Hrast, Jurij Trontelj, Maja Kokot, Nikola Minovski |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Microbiology (medical)
medicine.drug_class hERG raziskave zdravil Farmacevtska kemija RM1-950 intercalators 01 natural sciences Biochemistry Microbiology DNA gyrase Article drug discovery intercalating agents antibakterijska sredstva raziskave zdravil zaviralci DNA giraz zaviralci topoizomeraze IV interkalator novi zaviralci bakterijske topoizomeraze antibakterijska sredstva 03 medical and health sciences novi zaviralci bakterijske topoizomeraze udc:615.4:54 medicine Pharmacology (medical) General Pharmacology Toxicology and Pharmaceutics udc:615.4 030304 developmental biology antibacterials 0303 health sciences zaviralci DNA giraz biology Chemistry Drug discovery topoisomerase IV inhibitors topoisomerase II inhibitors DNA gyrase inhibitors Combinatorial chemistry 0104 chemical sciences 010404 medicinal & biomolecular chemistry antibacterials drug discovery DNA gyrase inhibitors topoisomerase IV inhibitors intercalators novel bacterial topoisomerase inhibitors Infectious Diseases Membrane zaviralci topoizomeraze IV Lipophilicity farmacevtska kemija biology.protein interkalator novel bacterial topoisomerase inhibitors Therapeutics. Pharmacology Antibacterial activity Selectivity Topoisomerase inhibitor |
| Zdroj: | Antibiotics Volume 10 Issue 7 Antibiotics, 30 str. : Ilustr., tabele, Vol. 10, no. 7, art. 862, 2021 COBISS-ID: 522975769 Antibiotics, Vol 10, Iss 862, p 862 (2021) Antibiotics, vol. 10, no. 7, 862, 2021. |
| ISSN: | 2079-6382 |
| DOI: | 10.3390/antibiotics10070862 |
| Popis: | Herein, we report the design of a focused library of novel bacterial topoisomerase inhibitors (NBTIs) based on innovative mainly monocyclic right-hand side fragments active against DNA gyrase and Topo IV. They exhibit a very potent and wide range of antibacterial activity, even against some of the most concerning hard-to-treat pathogens for which new antibacterials are urgently needed, as reported by the WHO and CDC. NBTIs enzyme activity and whole cell potency seems to depend on the fine-tuned lipophilicity/hydrophilicity ratio that governs the permeability of those compounds through the bacterial membranes. Lipophilicity of NBTIs is apparently optimal for passing through the membrane of Gram-positive bacteria, but the higher, although not excessive lipophilicity and suitable hydrophilicity seems to determine the passage through Gram-negative bacterial membranes. However, due to the considerable hERG inhibition, which is still at least two orders of magnitude away from MICs, continued optimization is required to realize their full potential. Nasl. z nasl. zaslona. Opis vira z dne 16. 7. 2021. Št. članka: 862. Abstract. Bibliografija: str. 28-30. ARRS ARRS |
| Databáze: | OpenAIRE |
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