Four New Anthraquinones with Histone Deacetylase Inhibitory Activity from Ventilago denticulata Roots
Abstract
:1. Introduction
2. Results and Discussion
2.1. Structure Characterization
2.2. HDAC Inhibitory Activity
2.3. Physicochemical Properties
2.4. Molecular Docking Study
2.5. MTT Assay
3. Materials and Methods
3.1. General Experimental Procedures
3.2. Plant Materials
3.3. Extraction and Isolation
3.4. HDAC Inhibitory Activity Assay
3.5. In Silico Physicochemical Properties
3.6. Molecular Docking
3.7. MTT Assay
4. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Sample Availability
References
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Position | δH Multiplicity (J in Hz) | |||
---|---|---|---|---|
1 (DMSO-d6) | 2 (CDCl3) | 3 (DMSO-d6) | 4 (CDCl3) | |
2 | 7.01 dd (1.7, 0.7) | 7.66 s | ||
4 | 7.52 s | 7.54 dd (1.7, 0.7) | 7.47 d (0.6) | |
5 | 7.22 d (2.4) | 7.81 dd (7.5, 1.1) | ||
6 | 7.67 dd (8.2, 7.5) | |||
7 | 6.68 s | 6.81 d (2.4) | 7.29 dd (8.2, 1.1) | |
1-COOCH3 | 3.98 s | |||
2-COOCH3 | 3.89 s | |||
3-CH3 | 2.36 s | 2.42 dd (0.7, 0.7) | 2.25 d (0.6) | 2.44 s |
5-CH3 | 2.45 s | 2.59 s | ||
6-OCH3 | 3.97 s | |||
7-OCH3 | 4.01 s | |||
8-OCH3 | 3.92 s | |||
1-OH | 12.28 s | 11.91 s | 13.65, s | |
4-OH | 12.34 s | |||
8-OH | 12.59 s | 13.03 s | 11.94 s |
Position | δC, Type | |||
---|---|---|---|---|
1 (DMSO-d6) | 2 (CDCl3) | 3 (DMSO-d6) | 4 (CDCl3) | |
1 | 157.3, C | 162.2, C | 149.6, C | 133.7, C |
2 | 127.6, C | 123.4, CH | 150.6, C | 121.7, CH |
3 | 144.2, C | 149.1, C | 130.1, C | 129.2, C |
4 | 120.4, CH | 121.2, CH | 121.4, CH | 159.9, C |
5 | 124.7, C | 126.8, C | 106.9, CH | 120.4, CH |
6 | 165.2, C | 158.5, C | 163.4, C | 137.6, CH |
7 | 106.8, CH | 145.7, C | 104.3, CH | 125.1, CH |
8 | 163.2, C | 157.0, C | 164.6, C | 162.8, C |
9 | 189.4, C | 192.2, C | 186.9, C | 192.5, C |
10 | 183.4, C | 183.8, C | 180.8, C | 181.6, C |
4a | 134.5, C | 135.0, C | 122.4, C | 146.6, C |
8a | 109.1, C | 113.6, C | 112.7, C | 115.9, C |
9a | 113.7, C | 113.7, C | 115.0, C | 114.3, C |
10a | 131.5, C | 131.0, C | 137.4, C | 133.6, C |
1-COO | 166.7, C | |||
2-COO | 166.2, C | |||
3-CH3 | 19.7, CH3 | 22.5, CH3 | 16.3, CH3 | 20.7, CH3 |
5-CH3 | 13.0, CH3 | 14.2, CH3 | ||
1-COOCH3 | 53.3, CH3 | |||
2-COOCH3 | 52.6, CH3 | |||
6-OCH3 | 61.2, CH3 | |||
7-OCH3 | 61.4, CH3 | |||
8-OCH3 | 56.3, CH3 |
Compounds | % Inhibition |
---|---|
Ventilanone M (2) | 61.27 |
Physcion (6) | 30.15 |
Emodin (9) | 17.30 |
TSA | 86.10 * |
Compounds | Physicochemical Properties | |||||
---|---|---|---|---|---|---|
MW (g/mol) | TPSA a (Å2) | Num. Rotatable Bonds | Num. H-Bond Acceptors | Num. H-Bond Donors | Log Po/w b | |
1 | 342.30 | 121.13 | 2 | 7 | 3 | 3.05 |
2 | 328.32 | 93.06 | 2 | 6 | 2 | 3.65 |
3 | 300.26 | 104.06 | 1 | 6 | 3 | 2.60 |
4 | 312.27 | 100.90 | 2 | 6 | 2 | 3.00 |
Compounds | Class I HDACs | Class II HDACs | ||||||||
---|---|---|---|---|---|---|---|---|---|---|
HDAC1 | HDAC2 | HDAC8 | HDAC4 | HDAC7 | ||||||
ΔG * | Ki ** | ΔG * | Ki ** | ΔG * | Ki ** | ΔG * | Ki ** | ΔG * | Ki ** | |
2 | −5.91 | 46.81 | −6.12 | 32.92 | −6.46 | 18.42 | −6.85 | 9.49 | −6.46 | 5.29 |
SAHA | −6.23 | 27.28 | −7.43 | 3.55 | −7.52 | 3.09 | −5.20 | 152.69 | −4.79 | 228.88 |
Cell Lines | IC50 Values (Mean ± SD; n = 3; μM) | |||||
---|---|---|---|---|---|---|
Compound 2 | Cisplatin | |||||
24 h | 48 h | 72 h | 24 h | 48 h | 72 h | |
HeLa cells | 240.46 ± 8.14 | 190.08 ± 2.97 | 160.87 ± 2.08 | 17.07 ± 1.00 | 9.97 ± 0.34 | 6.45 ± 0.13 |
A549 cells | >300 | 203.17 ± 6.56 | 177.32 ± 5.32 | 65.36 ± 8.11 | 11.44 ± 1.99 | 5.06 ± 0.01 |
MCF−7 cells | >300 | >300 | >300 | 29.17 ± 4.48 | 13.75 ± 1.81 | 10.42 ± 0.85 |
Vero cells | >300 | >300 | 273.47 ± 3.49 | 42.85 ± 2.38 | 12.36 ± 0.63 | 6.55 ± 0.81 |
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Hangsamai, N.; Photai, K.; Mahaamnart, T.; Kanokmedhakul, S.; Kanokmedhakul, K.; Senawong, T.; Pitchuanchom, S.; Nontakitticharoen, M. Four New Anthraquinones with Histone Deacetylase Inhibitory Activity from Ventilago denticulata Roots. Molecules 2022, 27, 1088. https://doi.org/10.3390/molecules27031088
Hangsamai N, Photai K, Mahaamnart T, Kanokmedhakul S, Kanokmedhakul K, Senawong T, Pitchuanchom S, Nontakitticharoen M. Four New Anthraquinones with Histone Deacetylase Inhibitory Activity from Ventilago denticulata Roots. Molecules. 2022; 27(3):1088. https://doi.org/10.3390/molecules27031088
Chicago/Turabian StyleHangsamai, Nattika, Kanokwan Photai, Thidathep Mahaamnart, Somdej Kanokmedhakul, Kwanjai Kanokmedhakul, Thanaset Senawong, Siripit Pitchuanchom, and Mongkol Nontakitticharoen. 2022. "Four New Anthraquinones with Histone Deacetylase Inhibitory Activity from Ventilago denticulata Roots" Molecules 27, no. 3: 1088. https://doi.org/10.3390/molecules27031088
APA StyleHangsamai, N., Photai, K., Mahaamnart, T., Kanokmedhakul, S., Kanokmedhakul, K., Senawong, T., Pitchuanchom, S., & Nontakitticharoen, M. (2022). Four New Anthraquinones with Histone Deacetylase Inhibitory Activity from Ventilago denticulata Roots. Molecules, 27(3), 1088. https://doi.org/10.3390/molecules27031088