Isolation and NMR Scaling Factors for the Structure Determination of Lobatolide H, a Flexible Sesquiterpene from Neurolaena lobata †
Abstract
:1. Introduction
2. Results and Discussion
3. Materials and Methods
3.1. General Procedures
3.2. Plant Material
3.3. Extraction and Isolation
3.4. Physical Characteristics of the New Compound
3.5. Computational Section
3.6. Antiproliferative MTT Assay
3.7. Cell Cycle Analysis by Flow Cytometry
3.8. Wound Healing Assay
3.9. Statistical Analysis
4. 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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Position | 1H | 13C |
---|---|---|
1a | 2.72 dd (11.0, 5.9) | 48.6 |
1b | 2.07 m | |
2 | 4.75 td (9.8, 5.9) | 69.2 |
3 | 5.25 d (9.8) | 133.9 |
4 | - | 135.1 |
5a | 2.76 dd (14.3, 5.1) | 44.0 |
5b | 2.32 dd (14.3, 1.6) | |
6 | 5.76 brd (5.1) | 70.8 |
7 | 2.93 d (7.9) | 52.9 |
8 | 5.50 t (9.9, 7.9) | 75.3 |
9 | 4.98 brd (9.9) | 129.3 |
10 | - | 142.7 |
11 | - | 136.4 |
12 | - | 169.4 |
13a | 6.30 d (3.2) | 121.2 |
13b | 5.60 d (3.2) | |
14 | 1.79 s | 18.7 |
15 | 1.53 s | 20.0 |
8-iVal | ||
1′ | - | 171.8 |
2′ | 2.15–2.17 m (2H) | 43.3 |
3′ | 2.05 m | 25.4 |
4′ | 0.92 d (6.2) | 22.3 |
5′ | 0.90 d (6.3) | 22.3 |
NMR Level//DFT Optimization Level | MAE (Isomer 1; Isomer 2; Isomer 3, Isomer 4) | sDP4+ (Isomer 1; Isomer 2; Isomer 3, Isomer 4) |
---|---|---|
mPW1PW91/6-311+G(2d,p)//B3LYP/6-31+G(d,p) | 2.32; 2.10; 2.57; 2.49 | 5.28%; 93.00%; 0.25%; 1.47% |
mPW1PW91/6-311+G(2d,p) SMD/CHCl3//B3LYP/6-31+G(d,p) | 2.06; 2.07; 2.16; 2.34 | 55.91%; 30.41%; 12.46%; 1.22% |
mPW1PW91/6-311+G(2d,p) SMD/CHCl3//mPW1PW91/6-311+G(2d,p) SMD/CHCl3 | 2.15; 1.89; 2.38; 2.41 | 3.40%; 96.26%; 0.19%; 0.16% |
NMR Level//DFT Optimization Level | MAE [(8R)-Epimer; (8S)-Epimer] | sDP4+ [(8R)-Epimer; (8S)-Epimer] |
---|---|---|
mPW1PW91/6-31G(d)//M06-2X/6-31G(d) | 1.63; 1.68 | (69.35%; 30.65%) |
mPW1PW91/6-31G(d) SMD/CHCl3//M06-2X/6-31G(d) | 1.40; 1.54 | (93.58%; 6.42%) |
M06/6-31G(d)//B3LYP/6-31+G(d,p) | 1.68; 2.01 | (99.13%; 0.87%) |
OPBE0/6-31G(d)//B3LYP/6-31+G(d,p) | 1.93; 2.35 | (99.79%; 0.21%) |
NMR Level//DFT Optimization Level | MAE (Isomer 1; Isomer 2; Isomer 3, Isomer 4) | sDP4+ (Isomer 1; Isomer 2; Isomer 3, Isomer 4) |
---|---|---|
mPW1PW91/6-31G(d) SMD/CHCl3//M06-2X/6-31G(d) | 2.42; 2.59; 2.62; 2.85 | (90.66% 3.14% 5.16% 1.04%) |
M06/6-31G(d)//B3LYP/6-31+G(d,p) | 3.12; 2.83; 3.19; 2.76 | (2.54%; 69.71%; 9.58%; 18.17%) |
Numbering | δExp (ppm) | δCalc (ppm) | Δδ (ppm) |
---|---|---|---|
C-1 | 79.28 | 78.78 | 0.50 |
C-2 | 32.17 | 31.26 | 0.91 |
C-3 | 35.34 | 36.89 | 1.55 |
C-4 | 146.48 | 152.97 | 6.49 |
C-5 | 56.15 | 56.06 | 0.09 |
C-6 | 67.25 | 64.33 | 2.92 |
C-7 | 49.59 | 48.55 | 1.04 |
C-8 | 18.43 | 19.65 | 1.22 |
C-9 | 36.55 | 35.90 | 0.65 |
C-10 | 41.93 | 44.33 | 2.40 |
C-11 | 26.26 | 27.81 | 1.55 |
C-12 | 21.32 | 19.60 | 1.72 |
C-13 | 16.44 | 15.72 | 0.72 |
C-14 | 11.82 | 10.57 | 1.25 |
C-15 | 108.03 | 105.99 | 2.04 |
MAE | N/A | N/A | 1.67 |
Numbering | δExp (ppm) | δCalc (ppm) | Δδ (ppm) |
---|---|---|---|
C-1 | 79.28 | 77.99 | 1.29 |
C-2 | 32.17 | 31.72 | 0.45 |
C-3 | 35.34 | 36.68 | 1.34 |
C-4 | 146.48 | 152.90 | 6.42 |
C-5 | 56.15 | 55.65 | 0.50 |
C-6 | 67.25 | 64.65 | 2.60 |
C-7 | 49.59 | 48.49 | 1.10 |
C-8 | 18.43 | 19.48 | 1.05 |
C-9 | 36.55 | 35.92 | 0.63 |
C-10 | 41.93 | 44.70 | 2.77 |
C-11 | 26.26 | 28.01 | 1.75 |
C-12 | 21.32 | 19.80 | 1.52 |
C-13 | 16.44 | 15.27 | 1.17 |
C-14 | 11.82 | 11.13 | 0.69 |
C-15 | 108.03 | 104.29 | 3.74 |
MAE | N/A | N/A | 1.80 |
NMR Level//DFT Optimization Level | MAE [(8R)-Epimer; (8S)-Epimer] | sDP4+ [(8R)-Epimer; (8S)-Epimer] |
---|---|---|
mPW1PW91/6-311+G(2d,p)//ωB97XD/6-31+G(d,p) | 1.82; 1.87 | (66.38%; 33.62%) |
mPW1PW91/6-311+G(2d,p) SMD/CHCl3//ωB97XD/6-31+G(d,p) SMD/CHCl3 | 1.60; 1.91 | (99.26%; 0.74%) |
NMR Level//DFT Optimization Level | MAE (Isomer 1; Isomer 2; Isomer 3, Isomer 4) |
---|---|
mPW1PW91/6-311+G(2d,p)//ωB97XD/6-31+G(d,p) | 2.33; 2.48; 2.58; 3.11 |
mPW1PW91/6-311+G(2d,p) SMD/CHCl3//ωB97XD/6-31+G(d,p) SMD/CHCl3 | 2.26; 2.42; 2.48; 3.23 |
Coupling Atoms | JExp (Hz) | Ji1 (Hz) | Ji2 (Hz) | ΔJi1 | ΔJi2 |
---|---|---|---|---|---|
1aH-2H | 5.90 | 6.62 | 0.93 | 0.72 | 4.97 |
2H-3H | 9.80 | 10.08 | 6.51 | 0.28 | 3.29 |
5aH-6H | 5.10 | 6.58 | 2.82 | 1.48 | 2.28 |
7H-8H | 7.90 | 4.33 | 3.28 | 3.57 | 4.62 |
8H-9H | 9.90 | 7.36 | 8.73 | 2.54 | 1.17 |
MAE | 1.72 | 3.27 |
Compound | IC50 Values (µM) [95% CI] | ||||
---|---|---|---|---|---|
HeLa | C33A | SiHa | NIH-3T3 | MRC-5 | |
1 | 16.62 [14.55–18.99] | 4.43 [3.62–5.43] | 2.82 [2.40–3.32] | 13.05 [11.44–14.90] | 14.82 [13.90–15.80] |
cisplatin | 12.14 [10.18–14.46] | 5.85 [5.37–6.38] | 4.29 [3.72–4.95] | 5.49 [4.76–6.35] | 5.17 [3.88–6.89] |
SI for 1 NIH-3T3/cell line | 0.79 | 2.95 | 4.63 | ||
SI for 1 MRC-5/cell line | 0.89 | 3.35 | 5.26 |
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Kovács, T.; Lajter, I.; Kúsz, N.; Schelz, Z.; Bózsity-Faragó, N.; Borbás, A.; Zupkó, I.; Krupitza, G.; Frisch, R.; Hohmann, J.; et al. Isolation and NMR Scaling Factors for the Structure Determination of Lobatolide H, a Flexible Sesquiterpene from Neurolaena lobata . Int. J. Mol. Sci. 2023, 24, 5841. https://doi.org/10.3390/ijms24065841
Kovács T, Lajter I, Kúsz N, Schelz Z, Bózsity-Faragó N, Borbás A, Zupkó I, Krupitza G, Frisch R, Hohmann J, et al. Isolation and NMR Scaling Factors for the Structure Determination of Lobatolide H, a Flexible Sesquiterpene from Neurolaena lobata . International Journal of Molecular Sciences. 2023; 24(6):5841. https://doi.org/10.3390/ijms24065841
Chicago/Turabian StyleKovács, Tibor, Ildikó Lajter, Norbert Kúsz, Zsuzsanna Schelz, Noémi Bózsity-Faragó, Anikó Borbás, István Zupkó, Georg Krupitza, Richard Frisch, Judit Hohmann, and et al. 2023. "Isolation and NMR Scaling Factors for the Structure Determination of Lobatolide H, a Flexible Sesquiterpene from Neurolaena lobata " International Journal of Molecular Sciences 24, no. 6: 5841. https://doi.org/10.3390/ijms24065841
APA StyleKovács, T., Lajter, I., Kúsz, N., Schelz, Z., Bózsity-Faragó, N., Borbás, A., Zupkó, I., Krupitza, G., Frisch, R., Hohmann, J., Vasas, A., & Mándi, A. (2023). Isolation and NMR Scaling Factors for the Structure Determination of Lobatolide H, a Flexible Sesquiterpene from Neurolaena lobata . International Journal of Molecular Sciences, 24(6), 5841. https://doi.org/10.3390/ijms24065841