Antimicrobial Evaluation of New Pyrazoles, Indazoles and Pyrazolines Prepared in Continuous Flow Mode
Abstract
:1. Introduction
2. Results
2.1. Antimicrobial Activity
2.2. Pharmacokinetic Properties and Drug-Likeness Prediction
3. Discussion
4. Materials and Methods
4.1. Bacterial Species Evaluated in this Study
4.2. Determination of the Minimal Inhibitory Concentrations (MICs)
4.3. Killing Curves
4.4. Preparation of Compounds Used in This Study and Synthetic Methods
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Strains | MIC (μg/mL) | ||||
---|---|---|---|---|---|
2 | 3 | 5 | 9 | R.A. | |
S. aureus 18 * | >128 | >128 | 128 | 4 | 256 (O) |
S. aureus 187 | >128 | >128 | 128 | 4 | 0.5 (O) |
S. aureus A * | >128 | >128 | 64 | 4 | 256 (O) |
S. epidermidis 22 * | >128 | >128 | 128 | 4 | 16 (O) |
S. epidermidis 180 | >128 | >128 | 128 | 4 | 0.25 (O) |
S. epidermidis 2R * | >128 | >128 | 64 | 4 | 256 (O) |
E. faecalis 1 °,# | 128 | 128 | >128 | 4 | 64 (V); 512 (T) |
E. faecalis 50 ° | >128 | 128 | >128 | 4 | 32 (V) |
E. faecalis 365 | 128 | 128 | >128 | 4 | 1 (V) |
E. faecium 300 ° | >128 | >128 | >128 | 4 | 256 (V) |
E. faecium 364 ° | >128 | >128 | >128 | 4 | 256 (V) |
E. faecium 503 | >128 | >128 | >128 | 4 | 1 (V) |
E. coli 224 | >128 | >128 | >128 | >128 | 0.125 (I) |
E. coli 462 ** | >128 | >128 | >128 | >128 | 16 (I) |
E. coli 477 ** | >128 | >128 | >128 | >128 | 16 (I) |
P. aeruginosa 1V ** | >128 | >128 | >128 | >128 | 32 (I) |
P. aeruginosa 265 **,°° | >128 | >128 | >128 | >128 | 16 (I): 16 (C) |
P. aeruginosa 403 | >128 | >128 | >128 | >128 | 1 (I) |
2 | 3 | 5 | 9 | |
---|---|---|---|---|
Physicochemical Property | ||||
MW (g/mol) | 278.23 | 309.11 | 222.29 | 333.38 |
Fraction Csp3 | 0.07 | 0.00 | 0.13 | 0.25 |
Rotatable bonds | 3 | 1 | 1 | 3 |
H-bond acceptors | 5 | 3 | 1 | 3 |
H-bond donors | 0 | 0 | 0 | 1 |
TPSA a (Å2) | 27.05 Å2 | 17.82 Å2 | 17.82 Å2 | 61.77 Å2 |
Lipophilicity | ||||
LogP b | 4.41 | 4.12 | 3.96 | 3.79 |
Water solubility | ||||
Solubility (mg/mL) c | 0.00555 mg/mL | 0.00387 mg/mL | 0.0111 mg/mL | 0.0118 mg/mL |
Solubility | moderately | moderately | moderately | moderately |
Pharmacokinetics | ||||
GI absorption | high | high | high | high |
BBB permeant | yes | yes | yes | yes |
Pgp substrate | no | no | no | no |
CYP1A2 inhibitor | yes | yes | yes | no |
CYP2C19 inhibitor | yes | yes | yes | yes |
CYP2C9 inhibitor | no | no | no | yes |
CYP2D6 inhibitor | yes | no | yes | no |
CYP3A4 inhibitor | no | no | no | yes |
Druglikeness | ||||
Lipinski violations | 0 | 1 violation: MLogP > 4.15 | 0 | 0 |
Medicinal chemistry | ||||
PAINS alerts | 0 | 0 | 0 | 0 |
Brenk alerts [46] | 0 | 1 (halogenated ring) | 0 | 1 (phthalimide) |
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Burke, A.; Di Filippo, M.; Spiccio, S.; Schito, A.M.; Caviglia, D.; Brullo, C.; Baumann, M. Antimicrobial Evaluation of New Pyrazoles, Indazoles and Pyrazolines Prepared in Continuous Flow Mode. Int. J. Mol. Sci. 2023, 24, 5319. https://doi.org/10.3390/ijms24065319
Burke A, Di Filippo M, Spiccio S, Schito AM, Caviglia D, Brullo C, Baumann M. Antimicrobial Evaluation of New Pyrazoles, Indazoles and Pyrazolines Prepared in Continuous Flow Mode. International Journal of Molecular Sciences. 2023; 24(6):5319. https://doi.org/10.3390/ijms24065319
Chicago/Turabian StyleBurke, Adam, Mara Di Filippo, Silvia Spiccio, Anna Maria Schito, Debora Caviglia, Chiara Brullo, and Marcus Baumann. 2023. "Antimicrobial Evaluation of New Pyrazoles, Indazoles and Pyrazolines Prepared in Continuous Flow Mode" International Journal of Molecular Sciences 24, no. 6: 5319. https://doi.org/10.3390/ijms24065319