Phenylspirodrimane with Moderate Reversal Effect of Multidrug Resistance Isolated from the Deep-Sea Fungus Stachybotrys sp. 3A00409
Abstract
:1. Introduction
2. Results and Discussion
2.1. Structural Determination
2.2. Biological Assays
2.3. Docking Analysis of Compound 8 and Verapamil with ABCB1
3. Materials and Methods
3.1. General Experimental Procedure
3.2. Fungal Material
3.3. Extraction and Isolation
3.4. Cells and Materials
3.5. Cell Cytotoxicity Assay
3.6. DOX Accumulation Assay
3.7. Molecular Docking Analysis
3.8. Data Analysis
4. Conclusions
Supplementary Materials
Author Contributions
Funding
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Name | Chemical Structure | Mechanism of Action | Adverse Effects | Phase |
---|---|---|---|---|
First generation | ||||
Verapamil | Calcium channel blocker | Hypotension, cardiotoxicity | Phase II | |
Cyclosporine A | P-gp inhibitor | Not significant | Phase II | |
Qunine | P-gp inhibitor | Myelosuppression | Phase III | |
Second generation | ||||
Dexverapamil | Calcium channel blocker | Cardiotoxicity | Phase II | |
Valspodar (PSC833) | P-gp inhibitor | Not significant | Phase III | |
Biricodar (VX-710) | P-gp inhibitor | Neutropenia | Phase II | |
Third generation | ||||
Laniquidar (R101933) | P-gp inhibitor | Mucositis and neutropenic fever | Phase II | |
Zosuquidar (LY335979) | P-gp inhibitor | Neurotoxicity | Phase III | |
Tariquidar (XR9576) | P-gp inhibitor | Not significant | Phase II | |
ONT-093 | P-gp inhibitor | Not significant | Phase I |
No. | 1 | 2 | ||
---|---|---|---|---|
δC | δH (J in Hz) | δC | δH (J in Hz) | |
1 | 23.9, CH2 | 0.94, m; 1.79, m | 23.9, CH2 | 0.94, m; 1.78, m |
2 | 24.9, CH2 | 1.37, m; 1.76, m | 24.9, CH2 | 1.36, m; 1.75, m |
3 | 73.5, CH | 3.17, brs | 73.5, CH | 3.16, brs |
4 | 36.5, C | 36.5, C | ||
5 | 39.9, CH | 2.01, d (8.3) | 39.9, CH | 2.00, m |
6 | 20.5, CH2 | 1.42, m; 1.46, m | 20.5, CH2 | 1.41, m; 1.45, m |
7 | 30.8, CH2 | 1.39, m; 1.52, m | 30.8, CH2 | 1.39, m; 1.51, m |
8 | 37.3, CH | 1.82, m | 37.3, CH | 1.81, m |
9 | 98.1, C | 98.1, C | ||
10 | 41.8, C | 41.9, C | ||
11 | 31.7, CH2 | 3.14, d (17.5) 2.79 (d, 17.0) | 31.7, CH2 | 3.14, d (17.9) 2.79, d (17.1) |
12 | 15.6, CH3 | 0.68, d (6.4) | 15.6, CH3 | 0.68, d (6.4) |
13 | 28.7, CH3 | 0.86, s | 28.7, CH3 | 0.86, s |
14 | 22.4, CH3 | 0.79, s | 22.4, CH3 | 0.79, s |
15 | 15.8, CH3 | 0.95, s | 15.8, CH3 | 0.95, s |
1′ | 117.1, C | 117.2 s | ||
2′ | 153.8, C | 153.9 s | ||
3′ | 101.1, CH | 6.64, s | 101.2, CH | 6.64, s |
4′ | 133.6, C | 133.5, C | ||
5′ | 112.5, C | 112.4, C | ||
6′ | 155.9, C | 155.9, C | ||
7′ | 167.2, C | 167.1, C | ||
8′ | 48.8, CH2 | 4.62, brs | 49.0, CH2 | 4.53, dd (16.2) 4.61, dd (16.2) |
9′ | 125.7, C | 126.8, C | ||
10′ | 152.8, C | 154.9, C | ||
11′ | 116.8, CH | 6.96, d (8.0) | 112.4, CH | 7.15, d (8.2) |
12′ | 128.2, CH | 7.17, t (7.6) | 128.7, CH | 7.34, t (7.8) |
13′ | 119.2, CH | 6.86, t (7.5) | 120.5, CH | 7.01, t (7.6) |
14′ | 128.6, CH | 7.31, d (6.9) | 129.0, CH | 7.36, dd (7.6, 1.6) |
15′ | 55.6, CH3 | 3.79 s | ||
3-OH | 4.09, d (2.9) | 4.11, d (2.6) |
Compound | IC50 ± SD μM (Fold Reversal) | |||
---|---|---|---|---|
KB | KBv200 | |||
Doxorubicin | 0.007 ± 0.008 | 3.706 ± 1.224 | ||
+5 μmol L−1 8 | 0.007 ± 0.007 | 1.00 | 2.414 ± 1.814 | 1.54 |
+10 μmol L−1 8 | 0.007 ± 0.007 | 1.00 | 1.897 ± 1.648 | 1.95 |
Navelbine | 0.001 ± 0.0001 | 2.514 ± 2.271 | ||
+5 μmol L−1 8 | 0.001 ± 0.0001 | 1.00 | 0.800 ± 0.240 | 3.14 |
+10 μmol L−1 8 | 0.001 ± 0.0001 | 1.00 | 0.517 ± 0.007 | 4.86 |
Cisplatin | 0.385 ± 0.204 | 0.810 ± 0.377 | ||
+5 μmol L−1 8 | 0.455 ± 0.234 | 0.84 | 0.913 ± 0.426 | 0.89 |
+10 μmol L−1 8 | 0.493 ± 0.228 | 0.77 | 1.081 ± 0.482 | 0.75 |
Hela | Hela/VCR | |||
Doxorubicin | 0.098 ± 0.039 | 0.789 ± 0.575 | ||
+5 μmol L−1 8 | 0.074 ± 0.029 | 1.32 | 0.553 ± 0.410 | 1.43 |
+10 μmol L−1 8 | 0.066 ± 0.018 | 1.48 | 0.324 ± 0.364 | 2.44 |
+20 μmol L−1 8 | 0.083 ± 0.010 | 1.18 | 0.101 ± 0.045 | 7.82 |
Cisplatin | 1.812 ± 1.075 | 0.873 ± 0.047 | ||
+5 μmol L−1 8 | 1.472 ± 0.861 | 1.23 | 0.954 ± 0.081 | 0.92 |
+10 μmol L−1 8 | 1.749 ± 0.956 | 1.04 | 1.032 ± 0.032 | 0.85 |
+20 μmol L−1 8 | 2.227 ± 1.289 | 0.81 | 1.363 ± 0.348 | 0.64 |
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Ma, X.; Wu, M.; Chen, Z.; Cao, F.; Zhong, T.; Luo, Z.; Shao, Z.; Zhang, Y.; Chen, L.; Zhang, Z. Phenylspirodrimane with Moderate Reversal Effect of Multidrug Resistance Isolated from the Deep-Sea Fungus Stachybotrys sp. 3A00409. Molecules 2024, 29, 1685. https://doi.org/10.3390/molecules29071685
Ma X, Wu M, Chen Z, Cao F, Zhong T, Luo Z, Shao Z, Zhang Y, Chen L, Zhang Z. Phenylspirodrimane with Moderate Reversal Effect of Multidrug Resistance Isolated from the Deep-Sea Fungus Stachybotrys sp. 3A00409. Molecules. 2024; 29(7):1685. https://doi.org/10.3390/molecules29071685
Chicago/Turabian StyleMa, Xinhua, Min Wu, Zhenwei Chen, Fan Cao, Tianhua Zhong, Zhuhua Luo, Zongze Shao, Yonghong Zhang, Limin Chen, and Zhiqiang Zhang. 2024. "Phenylspirodrimane with Moderate Reversal Effect of Multidrug Resistance Isolated from the Deep-Sea Fungus Stachybotrys sp. 3A00409" Molecules 29, no. 7: 1685. https://doi.org/10.3390/molecules29071685
APA StyleMa, X., Wu, M., Chen, Z., Cao, F., Zhong, T., Luo, Z., Shao, Z., Zhang, Y., Chen, L., & Zhang, Z. (2024). Phenylspirodrimane with Moderate Reversal Effect of Multidrug Resistance Isolated from the Deep-Sea Fungus Stachybotrys sp. 3A00409. Molecules, 29(7), 1685. https://doi.org/10.3390/molecules29071685