Combatting AMR: A molecular approach to the discovery of potent and non-toxic rhenium complexes active against C. albicans-MRSA co-infection
Нема приказа
Аутори
Sovari, Sara NasiriRadaković, Nataša
Roch, Paul
Crochet, Aurelien
Pavić, Aleksandar
Zobi, Fabio
Чланак у часопису (Објављена верзија)
Метаподаци
Приказ свих података о документуАпстракт
Antimicrobial resistance (AMR) is a major emerging threat to public health, causing serious issues in the successful prevention and treatment of persistent diseases. While the problem escalates, lack of financial incentive has lead major pharmaceutical companies to interrupt their antibiotic drug discovery programs. The World Health Organisation (WHO) has called for novel solutions outside the traditional development pathway, with emphasis on new classes of active compounds with non-classical mechanisms of action. Metal complexes are an untapped source of antibiotic potential owing to unique modes of action and a wider range of three-dimensional geometries as compared to purely organic compounds. In this study, we present the antimicrobial and antifungal efficacy of a family of rhenium tricarbonyl diimine complexes with varying ligands, charge and lipophilicity. Our study allowed the identification of potent and non-toxic complexes active in vivo against S. aureus infections at MIC dos...es as low as 300 ng/mL, as well as against C. albicans-MRSA mixed co-infection. The compounds are capable of suppressing the C. albicans morphogenetic yeast-to-hyphal transition, eradicating fungal-S. aureus co-infection, while showing no sign of cardio-, hepato-, hematotoxiciy or teratogenicity.
Кључне речи:
Zebrafish / Rhenium / MRSA / Co-infection / Candida / AntibioticИзвор:
European Journal of Medicinal Chemistry, 2021, 226Издавач:
- Elsevier France-Editions Scientifiques Medicales Elsevier, Issy-Les-Moulineaux
Финансирање / пројекти:
- Fonds de recherche du Centenaire de l'Universite de Fribourg [818]
- 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: 10.1016/j.ejmech.2021.113858
ISSN: 0223-5234
PubMed: 34562853
WoS: 000703119000038
Scopus: 2-s2.0-85115757734
Институција/група
Institut za molekularnu genetiku i genetičko inženjerstvoTY - JOUR AU - Sovari, Sara Nasiri AU - Radaković, Nataša AU - Roch, Paul AU - Crochet, Aurelien AU - Pavić, Aleksandar AU - Zobi, Fabio PY - 2021 UR - https://imagine.imgge.bg.ac.rs/handle/123456789/1477 AB - Antimicrobial resistance (AMR) is a major emerging threat to public health, causing serious issues in the successful prevention and treatment of persistent diseases. While the problem escalates, lack of financial incentive has lead major pharmaceutical companies to interrupt their antibiotic drug discovery programs. The World Health Organisation (WHO) has called for novel solutions outside the traditional development pathway, with emphasis on new classes of active compounds with non-classical mechanisms of action. Metal complexes are an untapped source of antibiotic potential owing to unique modes of action and a wider range of three-dimensional geometries as compared to purely organic compounds. In this study, we present the antimicrobial and antifungal efficacy of a family of rhenium tricarbonyl diimine complexes with varying ligands, charge and lipophilicity. Our study allowed the identification of potent and non-toxic complexes active in vivo against S. aureus infections at MIC doses as low as 300 ng/mL, as well as against C. albicans-MRSA mixed co-infection. The compounds are capable of suppressing the C. albicans morphogenetic yeast-to-hyphal transition, eradicating fungal-S. aureus co-infection, while showing no sign of cardio-, hepato-, hematotoxiciy or teratogenicity. PB - Elsevier France-Editions Scientifiques Medicales Elsevier, Issy-Les-Moulineaux T2 - European Journal of Medicinal Chemistry T1 - Combatting AMR: A molecular approach to the discovery of potent and non-toxic rhenium complexes active against C. albicans-MRSA co-infection VL - 226 DO - 10.1016/j.ejmech.2021.113858 ER -
@article{ author = "Sovari, Sara Nasiri and Radaković, Nataša and Roch, Paul and Crochet, Aurelien and Pavić, Aleksandar and Zobi, Fabio", year = "2021", abstract = "Antimicrobial resistance (AMR) is a major emerging threat to public health, causing serious issues in the successful prevention and treatment of persistent diseases. While the problem escalates, lack of financial incentive has lead major pharmaceutical companies to interrupt their antibiotic drug discovery programs. The World Health Organisation (WHO) has called for novel solutions outside the traditional development pathway, with emphasis on new classes of active compounds with non-classical mechanisms of action. Metal complexes are an untapped source of antibiotic potential owing to unique modes of action and a wider range of three-dimensional geometries as compared to purely organic compounds. In this study, we present the antimicrobial and antifungal efficacy of a family of rhenium tricarbonyl diimine complexes with varying ligands, charge and lipophilicity. Our study allowed the identification of potent and non-toxic complexes active in vivo against S. aureus infections at MIC doses as low as 300 ng/mL, as well as against C. albicans-MRSA mixed co-infection. The compounds are capable of suppressing the C. albicans morphogenetic yeast-to-hyphal transition, eradicating fungal-S. aureus co-infection, while showing no sign of cardio-, hepato-, hematotoxiciy or teratogenicity.", publisher = "Elsevier France-Editions Scientifiques Medicales Elsevier, Issy-Les-Moulineaux", journal = "European Journal of Medicinal Chemistry", title = "Combatting AMR: A molecular approach to the discovery of potent and non-toxic rhenium complexes active against C. albicans-MRSA co-infection", volume = "226", doi = "10.1016/j.ejmech.2021.113858" }
Sovari, S. N., Radaković, N., Roch, P., Crochet, A., Pavić, A.,& Zobi, F.. (2021). Combatting AMR: A molecular approach to the discovery of potent and non-toxic rhenium complexes active against C. albicans-MRSA co-infection. in European Journal of Medicinal Chemistry Elsevier France-Editions Scientifiques Medicales Elsevier, Issy-Les-Moulineaux., 226. https://doi.org/10.1016/j.ejmech.2021.113858
Sovari SN, Radaković N, Roch P, Crochet A, Pavić A, Zobi F. Combatting AMR: A molecular approach to the discovery of potent and non-toxic rhenium complexes active against C. albicans-MRSA co-infection. in European Journal of Medicinal Chemistry. 2021;226. doi:10.1016/j.ejmech.2021.113858 .
Sovari, Sara Nasiri, Radaković, Nataša, Roch, Paul, Crochet, Aurelien, Pavić, Aleksandar, Zobi, Fabio, "Combatting AMR: A molecular approach to the discovery of potent and non-toxic rhenium complexes active against C. albicans-MRSA co-infection" in European Journal of Medicinal Chemistry, 226 (2021), https://doi.org/10.1016/j.ejmech.2021.113858 . .