Biopharmaceutical Profiling of New Antitumor Pyrazole Derivatives
Abstract
:1. Introduction
2. Results and Discussion
2.1. Preliminary Screening
2.1.1. Molecular Descriptors
Comp. | MW | pKa(a) | nHDon | nHAcc | nBM | RBN | nAT | TPSA | MlogP | AlogP | AMR | Ui | Hy | Mv | ARR | Mp |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
BC2 | 294.8 | 9.85 | 3 | 4 | 13 | 2 | 30 | 101.9 | 2.59 | 3.09 | 79.2 | 3.81 | 1.25 | 0.69 | 0.55 | 0.73 |
BC3 | 308.8 | 8.5 | 2 | 4 | 13 | 3 | 33 | 91.0 | 2.45 | 3.08 | 82.9 | 3.81 | 0.46 | 0.67 | 0.52 | 0.72 |
BC5 | 370.9 | 8.84 | 2 | 4 | 19 | 3 | 40 | 91.0 | 3.7 | 4.59 | 102.6 | 4.32 | 0.31 | 0.7 | 0.63 | 0.74 |
BM2 | 274.4 | 8.91 | 2 | 4 | 13 | 3 | 33 | 91.0 | 1.91 | 2.42 | 78.1 | 3.81 | 0.45 | 0.65 | 0.55 | 0.69 |
BM3 | 288.4 | 8.05 | 2 | 4 | 13 | 3 | 36 | 91.0 | 2.18 | 2.9 | 83.2 | 3.81 | 0.41 | 0.64 | 0.52 | 0.69 |
BM5 | 350.5 | 8.25 | 2 | 4 | 19 | 3 | 43 | 91.0 | 3.44 | 4.41 | 102.8 | 4.32 | 0.27 | 0.67 | 0.63 | 0.71 |
BT2 | 260.4 | 8.8 | 3 | 4 | 13 | 2 | 30 | 101.9 | 2.05 | 2.42 | 74.4 | 3.81 | 1.25 | 0.67 | 0.58 | 0.71 |
BT3 | 274.4 | 7.91 | 3 | 4 | 13 | 2 | 33 | 101.9 | 2.32 | 2.91 | 79.4 | 3.81 | 1.2 | 0.65 | 0.55 | 0.69 |
BT5 | 336.5 | 8.1 | 2 | 4 | 19 | 3 | 40 | 91.0 | 3.20 | 3.93 | 97.8 | 4.32 | 0.3 | 0.68 | 0.65 | 0.72 |
2.1.2. Drug-Like Indices
Compound | LAI | GVWI * | Inflammat | Depressant | Psychotic | Hpertens | Hypnotic | Neoplasic | Infective |
---|---|---|---|---|---|---|---|---|---|
BC2 | 0 | 1 | 1 | 0 | 0 | 0 | 0 | 1 | 1 |
BC3 | 0 | 1 | 1 | 0 | 0 | 0 | 0 | 1 | 1 |
BC5 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
BM2 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 1 | 1 |
BM3 | 0 | 1 | 1 | 0 | 0 | 1 | 0 | 1 | 1 |
BM5 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
BT2 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 1 | 1 |
BT3 | 0 | 1 | 1 | 0 | 0 | 0 | 0 | 1 | 1 |
BT5 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
2.2. Quantitative HPLC Analysis
Compound | Slope ± SD | Intercept ± SD | R2 |
---|---|---|---|
BC2 | 45090 ± 602.1 | 7630 ± 2620 | 0.9991 |
BC3 | 42700 ± 559.5 | −930.1 ± 2435 | 0.9991 |
BC5 | 46360 ± 191.8 | 2016 ± 834.7 | 0.9999 |
BM2 | 52610 ± 350.9 | 915.1 ± 1527 | 0.9998 |
BM3 | 49990 ± 435.1 | 1287 ± 1894 | 0.9996 |
BM5 | 48000 ± 676.5 | −2474 ± 2944 | 0.9990 |
BT2 | 38650 ± 526.9 | 5702 ± 2293 | 0.9991 |
BT3 | 36090 ± 243.6 | 5524 ± 1051 | 0.9998 |
BT5 | 45620 ± 381.8 | 4301 ± 1647 | 0.9996 |
2.3. Equilibrium Solubility Study
2.4. Impact of the Molecular Descriptors on Solubility in Different Media
2.5. Biopharmaceutical in Silico Profiling
Compound | logD | Ref pH a | Aq Sol b (µg/mL) | Diff Coef (cm2/s*105) | Peff (cm/s*104) | fp (%) | RBP | MAD (mg) | %Fa c |
---|---|---|---|---|---|---|---|---|---|
BC2 | 2.59 | 6.9 | 12.4 | 0.81 | 2.03 | 19.9 | 0.82 | 112.2 | 55.4 |
BC3 | 2.64 | 6.14 | 49.9 | 0.78 | 3.29 | 16.03 | 0.78 | 744.9 | 99.6 |
BC5 | 3.54 | 6.64 | 11.1 | 0.69 | 3.99 | 6.68 | 0.71 | 244.7 | 79.9 |
BM2 | 2.22 | 6.58 | 13.3 | 0.8 | 1.79 | 24.68 | 0.88 | 101.6 | 42.9 |
BM3 | 2.29 | 5.92 | 48.4 | 0.77 | 2.88 | 17.73 | 0.78 | 618.6 | 99.5 |
BM5 | 3.19 | 6.4 | 9.4 | 0.69 | 3.47 | 7.3 | 0.75 | 165.6 | 72.4 |
BT2 | 1.88 | 6.41 | 23.3 | 0.84 | 1.64 | 25.48 | 0.94 | 158.7 | 81.2 |
BT3 | 1.89 | 5.71 | 87.3 | 0.8 | 2.56 | 17.05 | 0.82 | 972.8 | 99.6 |
BT5 | 2.81 | 6.2 | 16.2 | 0.71 | 3.03 | 6.9 | 0.78 | 231.9 | 85.5 |
3. Experimental Section
3.1. Chemicals
3.2. Quantitative HPLC Analysis
3.3. Evaluation of Experimental Thermodynamic Solubility
3.4. In Silico Tools
4. Conclusions
Acknowledgments
Author Contributions
Conflicts of Interest
References
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Anuta, V.; Nitulescu, G.M.; Dinu-Pîrvu, C.E.; Olaru, O.T. Biopharmaceutical Profiling of New Antitumor Pyrazole Derivatives. Molecules 2014, 19, 16381-16401. https://doi.org/10.3390/molecules191016381
Anuta V, Nitulescu GM, Dinu-Pîrvu CE, Olaru OT. Biopharmaceutical Profiling of New Antitumor Pyrazole Derivatives. Molecules. 2014; 19(10):16381-16401. https://doi.org/10.3390/molecules191016381
Chicago/Turabian StyleAnuta, Valentina, George Mihai Nitulescu, Cristina Elena Dinu-Pîrvu, and Octavian Tudorel Olaru. 2014. "Biopharmaceutical Profiling of New Antitumor Pyrazole Derivatives" Molecules 19, no. 10: 16381-16401. https://doi.org/10.3390/molecules191016381