Alendronic Acid as Ionic Liquid: New Perspective on Osteosarcoma
Abstract
:1. Introduction
2. Synthesis and Characterization of ALN–OSILs
3. Thermal Analysis of ALN–OSILs
4. Solubility Studies
5. Cytotoxicity on Human Cells
6. Experimental Section
6.1. General Procedure (A) for the Synthesis of ALN–OSILs with Organic Superbases as Cations
6.2. General Procedure (B) for the Preparation of ALN–OSILs with Ammonium and Methylmidazolium Cations
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
Abbreviations
IL | ionic liquid |
ALN | alendronic acid |
ALN–OSILs | alendronic acid-based ionic liquids and organic salts |
RTILs | Room Temperature Ionic Liquids |
API–OSILs | Active Pharmaceutical Ingredient Ionic Liquids and Organic Salts |
TMG | 1,1,3,3-tetramethylguanidine |
DBN | 1,5-diazabicyclo(4.3.0)non-5-ene |
Ch | choline |
C2OHMIM | 1-(2-hydroxyethyl)-3-methylimidazolium |
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Salt | Physical State | Tm/°C | Tcc/°C * | Tg/°C |
---|---|---|---|---|
[TMGH][ALN] | White solid | 162.7 | 107.1 | - |
[TMGH]2[ALN] | Colorless paste | - | - | 97.5 |
[DBNH][ALN] | White solid | 130.3; 133.2 | - | - |
[DBNH]2[ALN] | Colorless paste | - | - | 45.7 |
[C2OHMIM][ALN] | Colorless paste | - | - | 64.5 |
[C2OHMIM]2[ALN] | White solid | 153.0 (dec) | - | 46.3 |
[Ch][ALN] | White solid | 141.2 | - | 74.9 |
[Ch]2[ALN] | Colorless paste | - | - | 63.8 |
IC50/mM | ||||
---|---|---|---|---|
IL | GF | T47D | A549 | MG63 |
Paclitaxel | 1.91 × 10−5 ± 0.34 × 10−5 | 6.46 × 10−6 ± 0.57 × 10−6 | 4.08 × 10−6 ± 0.60 × 10−6 | 8.19 × 10−6 ± 1.03 × 10−6 |
ALN | 3.17 × 10−2 ± 0.12 × 10−2 | 4.09 × 10−3 ± 0.12 × 10−3 (*) | 8.10 × 10−3 ± 0.88 × 10−3 (*) | 5.55 × 10−4 ± 0.79 × 10−4 (*) |
[TMGH]Cl | 1.47 × 10−3 ± 0.40 × 10−3 | 1.94 × 10−4 ± 0.35 × 10−4 | 4.98 × 10−4 ± 0.55 × 10−4 | 2.46 × 10−4 ± 0.81 × 10−4 |
[DBNH]Cl | 3.80 × 10−5 ± 0.53 × 10−5 | 2.78 × 10−4 ± 0.19 × 10−4 | 9.13 × 10−3 ± 1.03 × 10−3 | 9.79 × 10−8 ± 1.76 × 10−8 |
[Ch]Cl | (a) | (a) | 5.99 × 10−3 ± 0.72 × 10−3 | 3.47 × 10−4 ± 0.52 × 10−4 |
[TMGH][ALN] | 7.19 × 10−3 ± 0.97 × 10−3 | 8.23 × 10−3 ± 0.99 × 10−3 | 2.54 × 10−3 ± 0.32 × 10−3 | 9.23 × 10−3 ± 1.12 × 10−3 |
[TMGH]2[ALN] | 1.11 × 10−3 ± 0.22 × 10−3 | 3.16 × 10−5 ± 0.25 × 10−5 | 5.14 × 10−4 ± 0.71 × 10−4 | 7.11 × 10−5 ± 0.85 × 10−5 |
[DBNH][ALN] | 7.20 × 10−2 ± 0.55 × 10−2 | (a) | 6.14 ± 0.87 | (a) |
[DBNH]2[ALN] | 6.01 × 10−5 ± 0.94 × 10−5 | (a) | 3.12 × 10−2 ± 0.45 × 10−2 | 1.02 ± 0.18 |
[C2OHMIM][ALN] | 2.19 ± 0.32 | 5.92 × 10−3 ± 0.69 × 10−3 (*) | 2.10 × 10−6 ± 0.37 × 10−6 (*) | 5.16 × 10−5 ± 0.67 × 10−5 (*) |
[C2OHMIM]2[ALN] | 4.07 × 10−4 ± 0.47 × 10−4 | 3.28 × 10−6 ± 0.40 × 10−6 (*) | (a) | 7.84 × 10−5 ± 0.98 × 10−5 (*) |
[Ch][ALN] | 1.87 × 10−1 ± 0.32 × 10−1 | 3.14 ± 0.43 | 6.66 × 10−2 ± 0.89 × 10−2 (*) | 4.10 × 10−1 ± 0.62 × 10−1 |
[Ch]2[ALN] | 4.92 × 10−3 ± 0.58 × 10−3 | 2.64 × 10−3 ± 0.38 × 10−3 | 5.41 × 10−3 ± 0.61 × 10−3 | 1.01 × 10−2 ± 0.14 × 10−2 |
IC50/mM | ||||
---|---|---|---|---|
IL | GF | T47D | A549 | MG63 |
Paclitaxel | 5.66 × 10−5 ± 0.94 × 10−5 | 9.28 × 10−6 ± 1.02 × 10−6 | 7.83 × 10−6 ± 0.85 × 10−6 | 1.10 × 10−6 ± 1.25 × 10−6 |
ALN | 9.26 × 10−2 ± 0.99 × 10−2 | 8.93 × 10−3 ± 1.53 × 10−3 (*) | 1.46 × 10−2 ± 0.43 × 10−2 (*) | 1.07 × 10−3 ± 0.26 × 10−3 (*) |
[TMGH][ALN] | 1.33 × 10−2 ± 0.51 × 10−2 | 1.84 × 10−2 ± 0.24 × 10−2 | 6.16 × 10−3 ± 0.94 × 10−3 | 1.64 × 10−2 ± 0.82 × 10−2 |
[TMGH]2[ALN] | 1.68 × 10−3 ± 0.27 × 10−3 | 1.87 × 10−5 ± 0.43 × 10−5 (*) | 9.84 × 10−4 ± 0.67 × 10−4 | 1.67 × 10−4 ± 0.25 × 10−4 |
[DBNH][ALN] | 2.55 × 10−1 ± 0.34 × 10−1 | (a) | 0.99 ± 0.07 | (a) |
[DBNH]2[ALN] | 1.65 × 10−4 ± 0.25 × 10−5 | (a) | 9.33 × 10−2 ± 1.00 × 10−2 | 1.14 ± 0.21 |
[C2OHMIM][ALN] | 4.54 ± 0.66 | 1.14 × 10−2 ± 0.25 × 10−2 (*) | 5.65 × 10−6 ± 0.46 × 10−6 (*) | 9.57 × 10−5 ± 0.91 × 10−5 (*) |
[C2OHMIM]2[ALN] | 6.21 × 10−4 ± 0.67 × 10−4 | 8.83 × 10−6 ± 0.94 × 10−6 (*) | (a) | 1.65 × 10−4 ± 0.26 × 10−4 (*) |
[Ch][ALN] | 7.33 × 10−1 ± 0.63 × 10−1 | 4.86 ± 0.55 | 7.84 × 10−2 ± 0.83 × 10−2 (*) | 6.85 × 10−1 ± 0.85 × 10−1 |
[Ch]2[ALN] | 8.57 × 10−3 ± 0.87 × 10−3 | 4.87 × 10−3 ± 0.65 × 10−3 | 8.94 × 10−3 ± 1.34 × 10−3 | 8.33 × 10−2 ± 0.93 × 10−2 |
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Teixeira, S.; Santos, M.M.; Fernandes, M.H.; Costa-Rodrigues, J.; Branco, L.C. Alendronic Acid as Ionic Liquid: New Perspective on Osteosarcoma. Pharmaceutics 2020, 12, 293. https://doi.org/10.3390/pharmaceutics12030293
Teixeira S, Santos MM, Fernandes MH, Costa-Rodrigues J, Branco LC. Alendronic Acid as Ionic Liquid: New Perspective on Osteosarcoma. Pharmaceutics. 2020; 12(3):293. https://doi.org/10.3390/pharmaceutics12030293
Chicago/Turabian StyleTeixeira, Sónia, Miguel M. Santos, Maria H. Fernandes, João Costa-Rodrigues, and Luís C. Branco. 2020. "Alendronic Acid as Ionic Liquid: New Perspective on Osteosarcoma" Pharmaceutics 12, no. 3: 293. https://doi.org/10.3390/pharmaceutics12030293
APA StyleTeixeira, S., Santos, M. M., Fernandes, M. H., Costa-Rodrigues, J., & Branco, L. C. (2020). Alendronic Acid as Ionic Liquid: New Perspective on Osteosarcoma. Pharmaceutics, 12(3), 293. https://doi.org/10.3390/pharmaceutics12030293