Interaction of Oxicam Derivatives with the Artificial Models of Biological Membranes—Calorimetric and Fluorescence Spectroscopic Study
Abstract
:1. Introduction
2. Materials and Methods
2.1. Chemicals
2.2. Experimental
2.2.1. Differential Scanning Calorimetry (DSC)
2.2.2. Fluorescence Spectroscopy
2.2.3. Prediction of ADMET Properties
3. Results
3.1. Differential Scanning Calorimetry
3.1.1. DSC Measurements of DPPC with Studied Compounds
3.1.2. DSC Measurements of DMPC with Studied Compounds
3.1.3. Comparison of the Results Obtained in DSC Studies for DPPC and DMPC
3.2. Fluorescence Spectroscopy
3.3. Prediction of ADMET Properties
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Compound Symbol | Chemical Structure |
---|---|
PR1 | |
PR2 | |
PR12 | |
PR26 | |
PR27 | |
PR38 | |
PRX (piroxicam) |
Parameter/ Optimal Value | Compound | |||||
---|---|---|---|---|---|---|
PR1 | PR2 | PR12 | PR26 | PR27 | PR38 | |
MW (molecular weight) optimal 100–600 | 503.19 | 503.15 | 521.14 | 521.18 | 521.14 | 521.18 |
nHA (number of hydrogen bond acceptors) optimal 0–12 | 7 | 8 | 8 | 7 | 8 | 7 |
nHD (number of hydrogen bond donors) optimal 0–7 | 0 | 0 | 0 | 0 | 0 | 0 |
TPSA (topological polar surface area) optimal 0–140 | 78 | 95 | 95 | 78 | 95 | 78 |
nRot (number of rotatable bonds) optimal 0–11 | 7 | 6 | 6 | 7 | 6 | 7 |
nRing (number of rings) optimal 0–6 | 5 | 5 | 5 | 5 | 5 | 5 |
nHet (number of heteroatoms) optimal 1–15 | 8 | 9 | 10 | 9 | 10 | 9 |
logP (log of the octanol/water partition coefficient) optimal 0–3 | 3.9 | 3.1 | 3.3 | 4.0 | 3.3 | 4.0 |
logD (logP at physiological pH) optimal 1–3 | 3.3 | 2.4 | 2.5 | 3.3 | 2.4 | 3.2 |
Parameter/ Optimal Value | Compound | |||||
PR1 | PR2 | PR12 | PR26 | PR27 | PR38 | |
QED (measure of drug-likeness based on the concept of desirability; attractive > 0.67, unattractive 0.49–0.67, too complex < 0.34) | 0.4 | 0.4 | 0.4 | 0.3 | 0.4 | 0.3 |
SA score (synthetic accessibility score is designed to estimate ease of synthesis of drug-like molecules; ≥6—difficult, <6—easy to synthesize) | 3.0 | 3.0 | 3.0 | 3.1 | 3.0 | 3.1 |
Fsp3 (number of sp3 hybridized carbons/total carbon count, correlating with melting point and solubility; ≥0.42 is considered a suitable value) | 0.3 | 0.2 | 0.2 | 0.3 | 0.2 | 0.2 |
Lipinski Rule (MW ≤ 500; logP ≤ 5; Hacc ≤ 10; Hdon ≤ 5; if two properties are out of range, a poor absorption or permeability is possible, one is acceptable) | all accepted | |||||
Pfizer Rule (compounds with a high log p (>3) and low TPSA (<75) are likely to be toxic) | all accepted | |||||
GSK Rule (MW ≤ 400; logP ≤ 4; compounds satisfying the GSK rule may have a more favorable ADMET profile) | all rejected |
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Maniewska, J.; Czyżnikowska, Ż.; Szczęśniak-Sięga, B.M.; Michalak, K. Interaction of Oxicam Derivatives with the Artificial Models of Biological Membranes—Calorimetric and Fluorescence Spectroscopic Study. Membranes 2022, 12, 791. https://doi.org/10.3390/membranes12080791
Maniewska J, Czyżnikowska Ż, Szczęśniak-Sięga BM, Michalak K. Interaction of Oxicam Derivatives with the Artificial Models of Biological Membranes—Calorimetric and Fluorescence Spectroscopic Study. Membranes. 2022; 12(8):791. https://doi.org/10.3390/membranes12080791
Chicago/Turabian StyleManiewska, Jadwiga, Żaneta Czyżnikowska, Berenika M. Szczęśniak-Sięga, and Krystyna Michalak. 2022. "Interaction of Oxicam Derivatives with the Artificial Models of Biological Membranes—Calorimetric and Fluorescence Spectroscopic Study" Membranes 12, no. 8: 791. https://doi.org/10.3390/membranes12080791