Membrane Permeability and Aqueous Stability Study of Linear and Cyclic Diarylheptanoids from Corylus maxima
Abstract
:1. Introduction
2. Materials and Methods
2.1. Plant Material
2.2. Solvents and Chemicals
2.3. Extraction and Sample Preparation
2.4. UHPLC-DAD-Orbitrap® MS Analyses
2.5. Isolation Procedures
2.6. NMR Spectroscopy
2.7. Determination of Aqueous Stability
2.8. Parallel Artificial Membrane Permeability Assay (PAMPA) Studies
3. Results and Discussion
3.1. Structure Elucidation by UHPLC-Orbitrap® MS and NMR
3.2. Determination of Aqueous Stability
3.3. Characterization of the Degradation Products by UHPLC-Orbitrap® MS
3.4. Parallel Artificial Membrane Permeability Assay (PAMPA) Studies
4. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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No. | [M-H]− (m/z) Experimental | [M-H]− (m/z) Calculated | Error (ppm) | Fragment Ions (m/z) (Molecular Formula, Mass Error in ppm) | Molecular Formula | Proposed Compound |
---|---|---|---|---|---|---|
1 | 507.1870 | 507.1866 | 1.76 | 327.1239 (C19H19O5, 3.67), 205.0864 (C12H13O3, 2.16), 179.0699 (C10H11O3, −1.81), 121.0280 (C7H5O2, −3.48) | C25H32O11 | hirsutanonol-5-O-β-D-glucopyranoside * |
1a | 327.1239 | 327.1233 | 3.69 | 205.0864 (C12H13O3, 2.16), 179.0699 (C10H11O3, −1.81), 121.0280 (C7H5O2, 3.48) | C19H20O5 | hirsutenone |
1b | 505.1718 | 505.1710 | 2.66 | 325.1080 (C19H17O5, 2.93), 203.0706 (C12H11O3, 1.56), 161.0598 (C10H9O2, 0.58), 135.0435 (C8H7O2, −3.98), 121.0280 (C7H5O2, −3.48) | C25H30O11 | 1,7-bis(3,4-dihydroxyphenyl)hepta-1,4-dien-3-one-glycoside |
1c | 505.1717 | 505.1710 | 2.25 | 325.1080 (C19H17O5, 2.93), 203.0706 (C12H11O3, 1.56), 161.0598 (C10H9O2, 0.58), 135.0434 (C8H7O2, −4.41), 121.0280 (C7H5O2, −3.48) | C25H30O11 | 1,7-bis(3,4-dihydroxyphenyl)hepta-1,4-dien-3-one-glycoside |
1d | 325.1082 | 325.1076 | 3.67 | 203.0706 (C12H11O3, 1.56), 161.0596 (C10H9O2, −0.94), 135.0438 (C8H7O2, −2.19), 121.0280 (C7H5O2, −3.48) | C19H18O5 | 1,7-bis(3,4-dihydroxyphenyl)hepta-1,4-dien-3-one |
2 | 477.1767 | 477.1761 | 3.85 | 327.1234 (C19H19O5, 2.09), 205.0863 (C12H13O3, 1.94), 179.0699 (C10H11O3, −1.81), 121.0281 (C7H5O2, −2.91) | C24H29O10 | oregonin * |
2a | 327.1239 | 327.1233 | 3.67 | 205.0864 (C12H13O3, 2.16), 179.0699 (C10H11O3, −1.81), 121.0281 (C7H5O2, −2.91) | C19H20O5 | hirsutenone |
2b | 475.1609 | 475.1604 | 2.20 | 325.1081 (C19H17O5, 3.30), 203.0704 (C12H11O3, 0.51), 161.0598 (C10H9O2, 0.58), 135.0441 (C8H7O2, 0.08) | C24H28O10 | 1,7-bis(3,4-dihydroxyphenyl)hepta-1,4-dien-3-one-xyloside |
2c | 325.1083 | 325.1076 | 3.78 | 203.0706 (C12H11O3, 1.56), 161.0597 (C10H9O2, 0.20), 135.0438 (C8H7O2, −2.06) | C19H18O5 | 1,7-bis(3,4-dihydroxyphenyl)hepta-1,4-dien-3-one |
3 | 327.1239 | 327.1233 | 3.67 | 205.0863 (C12H13O3, 1.94), 179.0699 (C10H11O3, −1.81), 121.0280 (C7H5O2, −3.48) | C19H20O5 | hirsutenone |
3a | 325.1082 | 325.1076 | 3.57 | 203.0706 (C12H11O3, 1.56), 161.0596 (C10H9O2, −0.94), 151.0385 (C8H7O3, −3.13), 135.0438 (C8H7O2, −2.06), 121.0281 (C7H5O2, −2.91), 109.0281 (C6H5O2, −2.81) | C19H18O5 | 1,7-bis(3,4-dihydroxyphenyl)hepta-1,4-dien-3-one-glycoside |
4 | 445.1870 | 445.1862 | 2.82 | 295.1339 (C19H19O3, 3.32), 189.0912 (C12H13O2, 1.20) | C24H30O8 | platyphyllonol-5-O-β-D-xylopyranoside |
4a | 295.1337 | 295.1334 | 2.91 | 189.0911 (C12H13O2, 0.39) | C19H20O3 | platyphyllenone |
5 | 295.1338 | 295.1334 | 3.22 | 189.0911 (C12H13O2, 0.39) | C19H20O3 | platyphyllenone |
5a | 313.1446 | 313.1440 | 3.78 | 163.0753 (C10H11O2, −0.42), 149.0595 (C9H9O2, −1.22) | C19H22O4 | platyphyllone, platyphyllonol |
6 | 473.1810 | 473.1812 | 2.68 | 293.1183 (C19H17O3, 3.74), 265.1220 (C18H17O2, −0.78), 251.1070 (C17H15O2, 1.59), 224.0834 (C15H22O2, 0.79), 210.0673 (C14H10O2, −1.14), 197.0597 (C13H9O2, 0.08) | C25H30O9 | alnusonol-11-O-β-D-glucopyranoside |
6a | 293.1184 | 293.1178 | 3.65 | 265.1221 (C18H17O2, −0.89), 251.1071 (C17H15O2, 1.71), 224.0834 (C15H22O2, 0.79), 210.0673 (C14H10O2, −1.14), 197.0596 (C13H9O2, −0.53) | C19H18O3 | alnusone |
7 | 293.1184 | 293.1178 | 3.85 | 265.1221 (C18H17O2, −0.89), 251.1071 (C17H15O2, 1.71), 224.0835 (C15H22O2, 1.47), 210.0673 (C14H10O2, −1.14), 197.0596 (C13H9O2, −0.53) | C19H18O3 | alnusone |
8 | 369.1350 | 369.1338 | 3.32 | 339.0873 (C19H15O6, 2.85) | C21H22O6 | giffonin F |
9 | 343.1187 | 343.1182 | 3.11 | 283.0976 (C17H15O4, 4.03), 269.0819 (C16H13O4, 3.99), 211.0756 (C14H11O2, 1.26) | C19H20O6 | carpinontriol B |
10 | 447.0934 | 447.0927 | 2.60 | 301.0343 (C15H9O7, 0.18), 300.0274 (C15H8O7, 3.27), 271.0247 (C14H7O6, 3.71), 255.0296 (C14H7O5, 2.96) | C21H20O11 | quercitrin * |
11 | 463.0885 | 463.0877 | 3.08 | 316.0223 (C15H8O8, 3.55), 287.0197 (C14H7O7, 4.10), 271.0249 (C14H7O6, 4.38), 242.0219 (C13H6O5, 2.27), 178.9976 (C8H3O5, 0.50) | C21H20O12 | myricitrin * |
11a | 925.1686 | 925.1675 | 1.98 | 779.1099 (C36H27O20, 0.45), 633.0499 (C30H17O16, −2.79), 435.0356 (C22H11O10, 0.85) | C42H38O24 | myricitrin dimer derivative |
11b | 925.1682 | 925.1675 | 1.39 | 779.1106 (C36H27O20, 1.32), 633.0532 (C30H17O16, 2.42), 597.0872 (C28H21O15, −1.42), 513.0441 (C27H13O11, −3.35), 435.0369 (C22H11O10, 3.85) | C42H38O24 | myricitrin dimer derivative |
11c | 895.1583 | 895.1569 | 2.20 | 749.1026 (C35H25O19, 4.79), 585.0311 (C29H13O14, 1.86), 557.0357 (C28H13O13, 0.14) | C41H36O23 | myricitrin derivative |
11d | 941.1633 | 941.1624 | 1.52 | 897.1686 (C41H37O23, −4.43), 751.1133 (C35H27O19, −1.81), 527.0229 (C27H11O12, −4.08), 393.0253 (C20H9O9, 1.63) | C42H38O25 | myricitrin derivative |
Aqueous Stability | log Pe PAMPA-BBB (n = 9) | log Pe PAMPA-GI (n = 9) | clog P | |||
---|---|---|---|---|---|---|
pH = 1.2 (n = 3) | pH = 6.8 (n = 3) | pH = 7.4 (n = 3) | ||||
hirsutanonol-5-O-β-D-glucopyranoside (1) | 97.03 ± 2.74 | 95.95 ± 1.52 * | 63.26 ± 1.93 * | n.d. | n.d. | 1.3 |
oregonin (2) | 98.67 ± 2.43 | 91.22 ± 3.01 * | 59.93 ± 2.85 * | n.d. | n.d. | 1.9 |
hirsutenone (3) | 99.63 ± 0.37 | 96.22 ± 2.87 | 83.80 ± 2.41 * | n.d. | n.d. | 3.9 |
platyphyllonol-5-O-β-D-xylopyranoside (4) | 100.47 ± 1.7 | 98.78 ± 0.91 | 89.79 ± 2.00 * | n.d. | n.d. | 2.6 |
platyphyllenone (5) | 99.45 ± 1.05 | 94.98 ± 2.10 * | 90.40 ± 1.52 * | −5.24 ± 0.25 | −4.92 ± 0.07 | 4.5 |
alnusonol-11-O-β-D-glucopyranoside (6) | 100.92 ± 2.92 | 74.03 ± 1.39 * | 61.76 ± 0.58 * | n.d. | n.d. | 1.6 |
alnusone (7) | 99.86 ± 0.50 | 101.55 ± 2.14 | 100.47 ± 1.87 | −4.66 ± 0.14 | −4.90 ± 0.17 | 4.2 |
giffonin F (8) | 99.97 ± 1.01 | 102.68 ± 2.45 | 100.92 ± 2.02 | n.d. | n.d. | 2.8 |
carpinontriol B (9) | 102.75 ± 1.09 | 101.51 ± 1.75 | 103.28 ± 1.81 | n.d. | −5.49 ± 0.30 | 1.6 |
quercitrin (10) | 100.91 ± 0.53 | 102.35 ± 1.85 | 100.75 ± 0.96 | n.d. | n.d. | 0.9 |
myricitrin (11) | 96.23 ± 2.46 | 99.94 ± 0.55 | 48.44 ± 6.15 * | n.d. | n.d. | 0.6 |
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Felegyi-Tóth, C.A.; Tóth, Z.; Garádi, Z.; Boldizsár, I.; Nedves, A.N.; Simon, A.; Felegyi, K.; Alberti, Á.; Riethmüller, E. Membrane Permeability and Aqueous Stability Study of Linear and Cyclic Diarylheptanoids from Corylus maxima. Pharmaceutics 2022, 14, 1250. https://doi.org/10.3390/pharmaceutics14061250
Felegyi-Tóth CA, Tóth Z, Garádi Z, Boldizsár I, Nedves AN, Simon A, Felegyi K, Alberti Á, Riethmüller E. Membrane Permeability and Aqueous Stability Study of Linear and Cyclic Diarylheptanoids from Corylus maxima. Pharmaceutics. 2022; 14(6):1250. https://doi.org/10.3390/pharmaceutics14061250
Chicago/Turabian StyleFelegyi-Tóth, Csenge Anna, Zsófia Tóth, Zsófia Garádi, Imre Boldizsár, Andrea Nagyné Nedves, Alexandra Simon, Kristóf Felegyi, Ágnes Alberti, and Eszter Riethmüller. 2022. "Membrane Permeability and Aqueous Stability Study of Linear and Cyclic Diarylheptanoids from Corylus maxima" Pharmaceutics 14, no. 6: 1250. https://doi.org/10.3390/pharmaceutics14061250
APA StyleFelegyi-Tóth, C. A., Tóth, Z., Garádi, Z., Boldizsár, I., Nedves, A. N., Simon, A., Felegyi, K., Alberti, Á., & Riethmüller, E. (2022). Membrane Permeability and Aqueous Stability Study of Linear and Cyclic Diarylheptanoids from Corylus maxima. Pharmaceutics, 14(6), 1250. https://doi.org/10.3390/pharmaceutics14061250