Antimicrobial Activity of Rhenium Di- and Tricarbonyl Diimine Complexes: Insights on Membrane-Bound S. aureus Protein Binding
Аутори
Schindler, KevinCortat, Youri
Nedyalkova, Miroslava
Crochet, Aurelien
Lattuada, Marco
Pavić, Aleksandar
Zobi, Fabio
Чланак у часопису (Објављена верзија)
Метаподаци
Приказ свих података о документуАпстракт
Antimicrobial resistance is one of the major human health threats, with significant impacts on the global economy. Antibiotics are becoming increasingly ineffective as drug-resistance spreads, imposing an urgent need for new and innovative antimicrobial agents. Metal complexes are an untapped source of antimicrobial potential. Rhenium complexes, amongst others, are particularly attractive due to their low in vivo toxicity and high antimicrobial activity, but little is known about their targets and mechanism of action. In this study, a series of rhenium di- and tricarbonyl diimine complexes were prepared and evaluated for their antimicrobial potential against eight different microorganisms comprising Gram-negative and -positive bacteria. Our data showed that none of the Re dicarbonyl or neutral tricarbonyl species have either bactericidal or bacteriostatic potential. In order to identify possible targets of the molecules, and thus possibly understand the observed differences in the anti...microbial efficacy of the molecules, we computationally evaluated the binding affinity of active and inactive complexes against structurally characterized membrane-bound S. aureus proteins. The computational analysis indicates two possible major targets for this class of compounds, namely lipoteichoic acids flippase (LtaA) and lipoprotein signal peptidase II (LspA). Our results, consistent with the published in vitro studies, will be useful for the future design of rhenium tricarbonyl diimine-based antibiotics.
Кључне речи:
tricarbonyl / S. aureus / rhenium / proteins / MRSA / membrane / LtaA / LspA / AutoDock / antimicrobialИзвор:
Pharmaceuticals, 2022, 15, 9Издавач:
- MDPI, Basel
Финансирање / пројекти:
- Swiss National Science Foundation [200021_196967]
- NCCR Bioinspired Materials
- Министарство науке, технолошког развоја и иновација Републике Србије, институционално финансирање - 200042 (Универзитет у Београду, Институт за молекуларну генетику и генетичко инжењерство) (RS-MESTD-inst-2020-200042)
DOI: 10.3390/ph15091107
ISSN: 1424-8247
WoS: 000859700800001
Scopus: 2-s2.0-85138657787
Институција/група
Institut za molekularnu genetiku i genetičko inženjerstvoTY - JOUR AU - Schindler, Kevin AU - Cortat, Youri AU - Nedyalkova, Miroslava AU - Crochet, Aurelien AU - Lattuada, Marco AU - Pavić, Aleksandar AU - Zobi, Fabio PY - 2022 UR - https://imagine.imgge.bg.ac.rs/handle/123456789/1528 AB - Antimicrobial resistance is one of the major human health threats, with significant impacts on the global economy. Antibiotics are becoming increasingly ineffective as drug-resistance spreads, imposing an urgent need for new and innovative antimicrobial agents. Metal complexes are an untapped source of antimicrobial potential. Rhenium complexes, amongst others, are particularly attractive due to their low in vivo toxicity and high antimicrobial activity, but little is known about their targets and mechanism of action. In this study, a series of rhenium di- and tricarbonyl diimine complexes were prepared and evaluated for their antimicrobial potential against eight different microorganisms comprising Gram-negative and -positive bacteria. Our data showed that none of the Re dicarbonyl or neutral tricarbonyl species have either bactericidal or bacteriostatic potential. In order to identify possible targets of the molecules, and thus possibly understand the observed differences in the antimicrobial efficacy of the molecules, we computationally evaluated the binding affinity of active and inactive complexes against structurally characterized membrane-bound S. aureus proteins. The computational analysis indicates two possible major targets for this class of compounds, namely lipoteichoic acids flippase (LtaA) and lipoprotein signal peptidase II (LspA). Our results, consistent with the published in vitro studies, will be useful for the future design of rhenium tricarbonyl diimine-based antibiotics. PB - MDPI, Basel T2 - Pharmaceuticals T1 - Antimicrobial Activity of Rhenium Di- and Tricarbonyl Diimine Complexes: Insights on Membrane-Bound S. aureus Protein Binding IS - 9 VL - 15 DO - 10.3390/ph15091107 ER -
@article{ author = "Schindler, Kevin and Cortat, Youri and Nedyalkova, Miroslava and Crochet, Aurelien and Lattuada, Marco and Pavić, Aleksandar and Zobi, Fabio", year = "2022", abstract = "Antimicrobial resistance is one of the major human health threats, with significant impacts on the global economy. Antibiotics are becoming increasingly ineffective as drug-resistance spreads, imposing an urgent need for new and innovative antimicrobial agents. Metal complexes are an untapped source of antimicrobial potential. Rhenium complexes, amongst others, are particularly attractive due to their low in vivo toxicity and high antimicrobial activity, but little is known about their targets and mechanism of action. In this study, a series of rhenium di- and tricarbonyl diimine complexes were prepared and evaluated for their antimicrobial potential against eight different microorganisms comprising Gram-negative and -positive bacteria. Our data showed that none of the Re dicarbonyl or neutral tricarbonyl species have either bactericidal or bacteriostatic potential. In order to identify possible targets of the molecules, and thus possibly understand the observed differences in the antimicrobial efficacy of the molecules, we computationally evaluated the binding affinity of active and inactive complexes against structurally characterized membrane-bound S. aureus proteins. The computational analysis indicates two possible major targets for this class of compounds, namely lipoteichoic acids flippase (LtaA) and lipoprotein signal peptidase II (LspA). Our results, consistent with the published in vitro studies, will be useful for the future design of rhenium tricarbonyl diimine-based antibiotics.", publisher = "MDPI, Basel", journal = "Pharmaceuticals", title = "Antimicrobial Activity of Rhenium Di- and Tricarbonyl Diimine Complexes: Insights on Membrane-Bound S. aureus Protein Binding", number = "9", volume = "15", doi = "10.3390/ph15091107" }
Schindler, K., Cortat, Y., Nedyalkova, M., Crochet, A., Lattuada, M., Pavić, A.,& Zobi, F.. (2022). Antimicrobial Activity of Rhenium Di- and Tricarbonyl Diimine Complexes: Insights on Membrane-Bound S. aureus Protein Binding. in Pharmaceuticals MDPI, Basel., 15(9). https://doi.org/10.3390/ph15091107
Schindler K, Cortat Y, Nedyalkova M, Crochet A, Lattuada M, Pavić A, Zobi F. Antimicrobial Activity of Rhenium Di- and Tricarbonyl Diimine Complexes: Insights on Membrane-Bound S. aureus Protein Binding. in Pharmaceuticals. 2022;15(9). doi:10.3390/ph15091107 .
Schindler, Kevin, Cortat, Youri, Nedyalkova, Miroslava, Crochet, Aurelien, Lattuada, Marco, Pavić, Aleksandar, Zobi, Fabio, "Antimicrobial Activity of Rhenium Di- and Tricarbonyl Diimine Complexes: Insights on Membrane-Bound S. aureus Protein Binding" in Pharmaceuticals, 15, no. 9 (2022), https://doi.org/10.3390/ph15091107 . .