Fluorinated Rh(I)–NHC Compounds as Potential Antibacterials Against Multidrug-Resistant Klebsiella pneumoniae Clinical Isolates Producing ESBL
Abstract
1. Introduction
2. Results and Discussion
2.1. Synthesis and Characterization of the Rh(I)–NHC Complexes
2.2. Isolation and Characterization of MDR Klebsiella pneumoniae
2.3. Antibacterial Activity Evaluation (MIC/MBC)
2.4. Time–Killing Kinetics of Rh(I)–NHC Complexes
2.5. ADMET Prediction/Pharmacokinetic Parameters
3. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Compound | MIC/MBC (µg/mL) | ||||||
---|---|---|---|---|---|---|---|
ATCC 25923 | ATCC 29213 | ATCC 43300 | ATCC 25922 | ATCC 29212 | ATCC 700603 | Streptococcus spp. | |
1 | NT | >250/>250 | NT | >250/>250 | NT | >250/>250 | NT |
2 | |||||||
3 | |||||||
4 | |||||||
5 | |||||||
6 | |||||||
7 | |||||||
8 | >250/>250 | 250/250 | >250/>250 | >250/>250 | >250/>250 | ||
9 | NT | >250/>250 | NT | NT | NT | ||
10 | |||||||
11 | |||||||
Rh–1 | 250/250 | 62.5/62.5 | 250/250 | 250/250 | 62.5/62.5 | 250/250 | |
Rh–2 | NT | >250/>250 | NT | >250/>250 | NT | NT | |
Rh–3 | 250/250 | 250/250 | 250/250 | >250/>250 | >250/>250 | ||
Rh–4 | 250/>250 | 250/250 | 250/250 | ||||
Rh–5 | 62.5/62.5 | >250/>250 | 62.5/62.5 | 15.6/15.6 | |||
Rh–6 | 62.5/250 | 62.5/62.5 | 250/>250 | 62.5/62.5 | |||
Rh–7 | NT | 3.9/15.6 | NT | 250/250 | NT | NT | |
Rh–8 | >250/>250 | >250/>250 | >250 | ||||
Rh–9 | 62.5/62.5 | 250/250 | 250/250 | 62.5/62.5 | 62.5/62.5 | ||
Rh–10 | 15.6/62.5 | ||||||
Rh–11 | 15.6/15.6 | 62.5/62.5 | 250/>250 | 0.97/15.6 | 15.6/15.6 | ||
LIN | 4/>32 | 1/8 | 4/>32 | >32/>32 | 2/>32 | NT | 1/8 |
GEN | 1/1 | 1/1 | >32/>32 | 0.25/1 | 4/16 | 0.5/0.5 | <0.125/<0.125 |
AMOX | <4/<4 | <4/<4 | 32/32 | <4/<4 | 4/4 | >256/>256 | 32/32 |
Compound | MIC/MBC (µg/mL) | |||||
---|---|---|---|---|---|---|
U–13685 | H–9871 | U–13815 | H–9866 | H–166 | S–401 | |
1 | >250/>250 | |||||
2 | ||||||
3 | ||||||
4 | ||||||
5 | ||||||
6 | ||||||
7 | ||||||
8 | ||||||
9 | ||||||
10 | ||||||
11 | ||||||
Rh–1 | 250/250 | 250/250 | 250/250 | >250/>250 | >250/>250 | >250/>250 |
Rh–2 | >250/>250 | >250/>250 | >250/>250 | |||
Rh–3 | 250/250 | 250/250 | 62.5/62.5 | |||
Rh–4 | >250/>250 | >250/>250 | 250/250 | |||
Rh–5 | 250/250 | |||||
Rh–6 | 250/>250 | >250/>250 | ||||
Rh–7 | >250/>250 | |||||
Rh–8 | ||||||
Rh–9 | ||||||
Rh–10 | ||||||
Rh–11 | 250/250 | 250/>250 | 250/250 | |||
GEN | <0.125/<0.125 | 1/1 | 1/1 | <0.125/<0.125 | 0.5/0.5 | <0.125/<0.125 |
AMOX | 64/64 | >256/>256 | >256/>256 | 128/128 | >256/>256 | >256/>256 |
MODEL | Azolium Salts | Rh(I)–NHC Complexes | ZP | CP | ||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
1 | 2 | 3 | 4 | 5 | 6 | 7 | 8 | 9 | 10 | 11 | Rh–1 | Rh–2 | Rh–3 | Rh–4 | Rh–5 | Rh–6 | Rh–7 | Rh–8 | Rh–9 | Rh–10 | Rh–11 | |||
ADMETsaR | ||||||||||||||||||||||||
Human intestinal absorption | + | + | – | – | + | + | + | + | + | + | + | + | – | + | + | – | + | + | + | – | + | – | + | + |
Human oral bioavailability | + | + | + | + | + | + | + | + | + | + | + | + | + | – | – | + | + | + | + | – | + | + | + | + |
Blood–brain barrier | + | + | + | + | + | + | + | + | + | + | + | + | + | + | + | + | + | + | + | + | + | + | + | + |
Mutagenesis (AMES) | + | + | + | + | + | + | + | – | – | + | – | – | – | – | – | – | – | – | – | – | – | – | + | – |
Acute oral toxicity (c) kg/mol | (III) | (III) | (III) | (III) | (III) | (III) | (III) | (III) | (III) | (III) | (III) | (III) | (III) | (III) | (III) | (III) | (III) | (III) | (III) | (III) | (III) | (III) | (III) | (III) |
Permeability/ Caco–2 | + | + | + | + | + | + | + | + | + | + | + | + | + | + | + | + | + | + | – | – | – | – | + | + |
Carcinogenicity | – | – | – | – | – | – | – | – | – | – | – | – | – | – | – | – | – | – | – | – | – | – | – | + |
Hepatotoxicity | – | – | – | + | + | – | + | – | – | – | – | – | – | – | – | + | – | – | – | – | – | – | + | – |
Fish aquatic toxicity | + | + | + | + | + | + | + | + | + | + | + | + | + | + | + | + | + | + | + | + | + | + | – | + |
Crustacean aquatic toxicity | + | + | + | + | + | + | + | + | + | + | + | + | + | + | + | + | + | + | + | + | + | + | – | + |
SwissADME | ||||||||||||||||||||||||
Solubility in water (Log S) SILICOS–IT (–) | 3.78 | 4.07 | 4.07 | 4.07 | 4.35 | 4.35 | 4.62 | 4.67 | 4.67 | 4.67 | 5.53 | 6.10 | 6.74 | 6.74 | 6.74 | 7.0 | 7.0 | 7.26 | 7.29 | 7.29 | 7.29 | 8.10 | 5.0 | 2.1 |
Gastrointestinal absorption | + | + | – | – | – | + | + | + | + | + | + | + | – | – | – | – | – | – | – | – | – | – | + | + |
Similarity to drugs “LIPINSKI” | + | + | + | + | + | + | + | + | + | + | + | + | + | + | + | + | + | + | – | – | – | – | + | + |
Synthetic accessibility | 1.77 | 1.81 | 2.19 | 2.11 | 2.25 | 1.97 | 1.90 | 1.86 | 1.94 | 2.30 | 2.16 | 3.56 | 4.09 | 4.10 | 4.12 | 4.13 | 4.10 | 4.12 | 4.14 | 4.18 | 4.24 | 4.33 | 2.67 | / |
Lead resemblance | – | – | – | – | – | – | – | – | – | – | – | – | – | – | – | – | – | – | – | – | – | – | – | – |
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Turcio-García, L.Á.; Parra-Unda, R.; Valdés, H.; Hernández-Ortega, S.; Valenzuela-Ramirez, G.G.; Ahumada-Santos, Y.P.; Sánchez-Lugo, Y.; Reyes-Márquez, V.; Morales-Morales, D. Fluorinated Rh(I)–NHC Compounds as Potential Antibacterials Against Multidrug-Resistant Klebsiella pneumoniae Clinical Isolates Producing ESBL. Pharmaceutics 2025, 17, 973. https://doi.org/10.3390/pharmaceutics17080973
Turcio-García LÁ, Parra-Unda R, Valdés H, Hernández-Ortega S, Valenzuela-Ramirez GG, Ahumada-Santos YP, Sánchez-Lugo Y, Reyes-Márquez V, Morales-Morales D. Fluorinated Rh(I)–NHC Compounds as Potential Antibacterials Against Multidrug-Resistant Klebsiella pneumoniae Clinical Isolates Producing ESBL. Pharmaceutics. 2025; 17(8):973. https://doi.org/10.3390/pharmaceutics17080973
Chicago/Turabian StyleTurcio-García, Luis Ángel, Ricardo Parra-Unda, Hugo Valdés, Simón Hernández-Ortega, Gladymar Guadalupe Valenzuela-Ramirez, Yesmi Patricia Ahumada-Santos, Yesenia Sánchez-Lugo, Viviana Reyes-Márquez, and David Morales-Morales. 2025. "Fluorinated Rh(I)–NHC Compounds as Potential Antibacterials Against Multidrug-Resistant Klebsiella pneumoniae Clinical Isolates Producing ESBL" Pharmaceutics 17, no. 8: 973. https://doi.org/10.3390/pharmaceutics17080973
APA StyleTurcio-García, L. Á., Parra-Unda, R., Valdés, H., Hernández-Ortega, S., Valenzuela-Ramirez, G. G., Ahumada-Santos, Y. P., Sánchez-Lugo, Y., Reyes-Márquez, V., & Morales-Morales, D. (2025). Fluorinated Rh(I)–NHC Compounds as Potential Antibacterials Against Multidrug-Resistant Klebsiella pneumoniae Clinical Isolates Producing ESBL. Pharmaceutics, 17(8), 973. https://doi.org/10.3390/pharmaceutics17080973