Computer-Aided Drug Design and Synthesis of Rhenium Clotrimazole Antimicrobial Agents
DOKPE
- Cortat, Youri University of Fribourg
- Nedyalkova, Miroslava ORCID University of Fribourg
- Schindler, Kevin ORCID University of Fribourg
- Kadakia, Parth University of Fribourg
- Demirci, Gozde ORCID University of Fribourg
- Nasiri Sovari, Sara University of Fribourg
- Crochet, Aurélien ORCID University of Fribourg
- Salentinig, Stefan University of Fribourg
- Lattuada, Marco University of Fribourg
- Mamula Steiner, Olimpia ORCID Haute école d’Ingénierie et d’Architecture, Fribourg
- Zobi, Fabio ORCID Fribourg
- 2023
Published in:
- Antibiotics. - Basel, Switzerland: MDPI. - 2023, vol. 12, no. 3, p. 1-17
English
In the context of the global health issue caused by the growing occurrence of antimicrobial resistance (AMR), the need for novel antimicrobial agents is becoming alarming. Inorganic and organometallic complexes represent a relatively untapped source of antibiotics. Here, we report a computer-aided drug design (CADD) based on a ‘scaffold-hopping’ approach for the synthesis and antibacterial evaluation of fac-Re(I) tricarbonyl complexes bearing clotrimazole (ctz) as a monodentate ligand. The prepared molecules were selected following a pre-screening in silico analysis according to modification of the 2,2′-bipyridine (bpy) ligand in the coordination sphere of the complexes. CADD pointed to chiral 4,5-pinene and 5,6-pinene bipyridine derivatives as the most promising candidates. The corresponding complexes were synthesized, tested toward methicillin-sensitive and -resistant S. aureus strains, and the obtained results evaluated with regard to their binding affinity with a homology model of the S. aureus MurG enzyme. Overall, the title species revealed very similar minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values as those of the reference compound used as the scaffold in our approach. The obtained docking scores advocate the viability of ‘scaffold-hopping’ for de novo design, a potential strategy for more cost- and time-efficient discovery of new antibiotics.
- Faculty
- Faculté des sciences et de médecine
- Department
- Département de Chimie
- Language
-
- English
- Classification
- Chemistry
- License
- CC BY
- Open access status
- gold
- Identifiers
-
- DOI 10.3390/antibiotics12030619
- ISSN 2079-6382
- Persistent URL
- https://folia.unifr.ch/unifr/documents/330407
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