Strong Antibiotic Activity of the Myxocoumarin Scaffold in vitro and in vivo
Authors
Hertrampf, GesaKusserow, Kalina
Vojnović, Sandra
Pavić, Aleksandar
Mueller, Jonas, I
Nikodinović-Runić, Jasmina
Gulder, Tobias A. M.
Article (Published version)
Metadata
Show full item recordAbstract
The increasing emergence of resistances against established antibiotics is a substantial threat to human health. The discovery of new compounds with potent antibiotic activity is thus of utmost importance. Within this work, we identify strong antibiotic activity of the natural product myxocoumarin B from Stigmatella aurantiaca MYX-030 against a range of clinically relevant bacterial pathogens, including clinical isolates of MRSA. A focused library of structural analogs was synthesized to explore initial structure-activity relationships and to identify equipotent myxocoumarin derivatives devoid of the natural nitro substituent to significantly streamline synthetic access. The cytotoxicity of the myxocoumarins as well as their potential to cure bacterial infections in vivo was established using a zebrafish model system. Our results reveal the exceptional antibiotic activity of the myxocoumarin scaffold and hence its potential for the development of novel antibiotics.
Keywords:
structure-activity relationships / Staphylococcus aureus / natural products / myxocoumarins / antibioticsSource:
Chemistry-A European Journal, 2022, 28, 32Publisher:
- Wiley-V C H Verlag Gmbh, Weinheim
Funding / projects:
- German Research Foundation [DFG GU 1233/1-1]
- Ministry of Science, Technological Development and Innovation of the Republic of Serbia, institutional funding - 200042 (University of Belgrade, Institute of Molecular Genetics and Genetic Engineering) (RS-MESTD-inst-2020-200042)
- DAAD (Deutscher Akademischer Austauschdienst, Bilateral Project of Germany) [TAMG - 2020/2021]
- Projekt DEAL
DOI: 10.1002/chem.202200394
ISSN: 0947-6539
WoS: 000787336900001
Scopus: 2-s2.0-85128802967
Collections
Institution/Community
Institut za molekularnu genetiku i genetičko inženjerstvoTY - JOUR AU - Hertrampf, Gesa AU - Kusserow, Kalina AU - Vojnović, Sandra AU - Pavić, Aleksandar AU - Mueller, Jonas, I AU - Nikodinović-Runić, Jasmina AU - Gulder, Tobias A. M. PY - 2022 UR - https://imagine.imgge.bg.ac.rs/handle/123456789/1553 AB - The increasing emergence of resistances against established antibiotics is a substantial threat to human health. The discovery of new compounds with potent antibiotic activity is thus of utmost importance. Within this work, we identify strong antibiotic activity of the natural product myxocoumarin B from Stigmatella aurantiaca MYX-030 against a range of clinically relevant bacterial pathogens, including clinical isolates of MRSA. A focused library of structural analogs was synthesized to explore initial structure-activity relationships and to identify equipotent myxocoumarin derivatives devoid of the natural nitro substituent to significantly streamline synthetic access. The cytotoxicity of the myxocoumarins as well as their potential to cure bacterial infections in vivo was established using a zebrafish model system. Our results reveal the exceptional antibiotic activity of the myxocoumarin scaffold and hence its potential for the development of novel antibiotics. PB - Wiley-V C H Verlag Gmbh, Weinheim T2 - Chemistry-A European Journal T1 - Strong Antibiotic Activity of the Myxocoumarin Scaffold in vitro and in vivo IS - 32 VL - 28 DO - 10.1002/chem.202200394 ER -
@article{ author = "Hertrampf, Gesa and Kusserow, Kalina and Vojnović, Sandra and Pavić, Aleksandar and Mueller, Jonas, I and Nikodinović-Runić, Jasmina and Gulder, Tobias A. M.", year = "2022", abstract = "The increasing emergence of resistances against established antibiotics is a substantial threat to human health. The discovery of new compounds with potent antibiotic activity is thus of utmost importance. Within this work, we identify strong antibiotic activity of the natural product myxocoumarin B from Stigmatella aurantiaca MYX-030 against a range of clinically relevant bacterial pathogens, including clinical isolates of MRSA. A focused library of structural analogs was synthesized to explore initial structure-activity relationships and to identify equipotent myxocoumarin derivatives devoid of the natural nitro substituent to significantly streamline synthetic access. The cytotoxicity of the myxocoumarins as well as their potential to cure bacterial infections in vivo was established using a zebrafish model system. Our results reveal the exceptional antibiotic activity of the myxocoumarin scaffold and hence its potential for the development of novel antibiotics.", publisher = "Wiley-V C H Verlag Gmbh, Weinheim", journal = "Chemistry-A European Journal", title = "Strong Antibiotic Activity of the Myxocoumarin Scaffold in vitro and in vivo", number = "32", volume = "28", doi = "10.1002/chem.202200394" }
Hertrampf, G., Kusserow, K., Vojnović, S., Pavić, A., Mueller, J. I., Nikodinović-Runić, J.,& Gulder, T. A. M.. (2022). Strong Antibiotic Activity of the Myxocoumarin Scaffold in vitro and in vivo. in Chemistry-A European Journal Wiley-V C H Verlag Gmbh, Weinheim., 28(32). https://doi.org/10.1002/chem.202200394
Hertrampf G, Kusserow K, Vojnović S, Pavić A, Mueller JI, Nikodinović-Runić J, Gulder TAM. Strong Antibiotic Activity of the Myxocoumarin Scaffold in vitro and in vivo. in Chemistry-A European Journal. 2022;28(32). doi:10.1002/chem.202200394 .
Hertrampf, Gesa, Kusserow, Kalina, Vojnović, Sandra, Pavić, Aleksandar, Mueller, Jonas, I, Nikodinović-Runić, Jasmina, Gulder, Tobias A. M., "Strong Antibiotic Activity of the Myxocoumarin Scaffold in vitro and in vivo" in Chemistry-A European Journal, 28, no. 32 (2022), https://doi.org/10.1002/chem.202200394 . .