Chrysosporazines Revisited: Regioisomeric Phenylpropanoid Piperazine P-Glycoprotein Inhibitors from Australian Marine Fish-Derived Fungi
Abstract
1. Introduction
2. Results and Discussion
3. Materials and Methods
3.1. General Experimental Procedures
3.2. Fungal Isolation
3.3. Fungal Taxonomy
3.4. Global Natural Product Social (GNPS) Molecular Networking
3.5. Fractionation of a Scaled Up PDA Culture of Aspergillus sp. CMB-F661
3.6. Media MATRIX Cultivation Profiling of Aspergillus sp. CMB-F661
3.7. Precursor-Directed Biosynthesis Cultivation Profiling of Aspergillus sp. CMB-F661
3.8. Scaled-Up Cultivation of Aspergillus sp. CMB-F661 on PDA with Sodium Nicotinate
3.9. Scaled-Up Cultivation of Aspergillus sp. CMB-F661 on PDA with Sodium Isonicotinate
3.10. Fractionation of a Scaled Up M1 Culture of Spiromastix sp. CMB-F455
3.11. Media MATRIX Cultivation Profiling of Spiromastix sp. CMB-F455
3.12. Precursor-Directed Biosynthesis Cultivation Profiling of Spiromastix sp. CMB-F455
3.13. Acid Hydrolysis and Chemical Correlation of 2, 4, 6 and 7 to the Common Product 10
3.14. Antibacterial Assay
3.15. Antifungal Assay
3.16. Cytotoxicity (MTT) Assay
3.17. P-Glycoprotein Mediated MDR Reversal Assay
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 | (1) δH, Multi (J in Hz) | (3) δH, Multi (J in Hz) | (5) δH, Multi (J in Hz) |
---|---|---|---|
1 | a. 4.14, dd (13.8, 3.9) | a. 4.25, dd (13.3, 3.8) | a. 4.19, dd (14.5, 4.0) |
b. 2.94, m | b. 3.03, m | b. 2.98, m | |
2 | 3.84, ddd (10.6, 10.6, 3.9) | 3.87, ddd (11.2, 8.8, 3.8) | 3.92, ddd (14.5, 10.3, 3.7) |
3 | 4.47, d (10.6) | 4.56, d (8.8) | 4.56, d (10.3) |
5/9 | 7.35, m | 7.26, m | 7.40, m |
6/8 | 7.44, m | 7.35, m | 7.46, m |
7 | 7.37, m | 7.29, m | 7.40, m |
1′ | a. 4.57, dd (13.3, 1.2) | a. 4.56, m | a. 4.55, dd (13.4, 1.3) |
b. 2.95, m | b. 3.01, m | b. 2.99, m | |
2′ | 4.21, m | 4.21, m | 4.23, m |
3′ | a. 2.90, dd (13.5, 8.1) | a. 2.88, dd (13.5, 8.3) | a. 2.90, dd (13.4, 8.6) |
b. 2.86, dd (13.5, 6.6) | b. 2.83, dd (13.5, 6.3) | b. 2.85, dd (13.4, 6.4) | |
4′ | - | - | - |
5′ | 6.54, d (1.2) | 6.54, d (1.3) | 6.54, d (1.4) |
9′ | 6.55, d (1.2) | 6.55, d (1.3) | 6.55, d (1.4) |
4″ | 6.60, d (7.8) | - | 7.89, s |
5″ | 7.44, m | 8.57, dd (4.7, 1.8) | - |
6″ | 7.39, m | 7.44, ddd (7.8, 4.7) | 8.64, d (4.7) |
7″ | 8.04, dd (7.7, 1.4) | 8.34, dd (7.8, 1.8) | 7.88, d (4.7) |
1-NCOCH3 | - | - | - |
1-NCOCH3 | 1.70, s | 1.68, s | 1.70, s |
6′-OCH2 | 5.94/5.93, ABq | 5.95/5.93, ABq | 5.95/5.94, ABq |
8′-OCH3 | 3.79, s | 3.78, s | 3.78, s |
Position | (1) δC, Type | (3) δC, Type | (5) δC, Type |
---|---|---|---|
1 | 40.1, CH2 | 40.4, CH2 | 40.1, CH2 |
2 | 57.8, CH | 58.6, CH | 58.2, CH |
3 | 46.3, CH | 48.8, CH | 43.7, CH |
4 | 140.4 A, C | 140.7, C | 139.4, C |
5/9 | 129.3, CH | 129.3, CH | 129.2A, CH |
6/8 | 129.1, CH | 128.6, CH | 129.1A, CH |
7 | 127.6, CH | 127.1, CH | 127.9, CH |
1′ | 44.6, CH2 | 45.0, CH2 | 44.8, CH2 |
2′ | 54.6, CH | 54.9, CH | 54.6, CH |
3′ | 34.9, CH2 | 35.0, CH2 | 34.8, CH2 |
4′ | 132.5, C | 132.6, C | 132.6, C |
5′ | 103.3, CH | 103.4, CH | 103.3, CH |
6′ | 148.3, C | 148.2, C | 148.3, C |
7′ | 133.0, C | 133.4, C | 133.3, C |
8′ | 143.0, C | 143.1, C | 143.0, C |
9′ | 109.0, CH | 109.1, CH | 109.0, CH |
1″ | 163.9, C | 163.2, C | 162.3, C |
2″ | 127.4, C | 122.9 A, C | 134.4, C |
3″ | 140.3 A, C | 158.4, C | 133.7, C |
4″ | 126.9 B, CH | - | 148.6, CH |
5″ | 132.3, CH | 152.6, CH | - |
6″ | 127.0 B, CH | 122.8 A, CH | 148.3, CH |
7″ | 127.6, CH | 135.6, CH | 120.2, CH |
1-NCOCH3 | 168.4, C | 168.6, C | 168.5, C |
1-NCOCH3 | 20.8, CH3 | 20.8, CH3 | 20.8, CH3 |
6′-OCH2 | 101.0, CH2 | 101.0, CH2 | 101.0, CH2 |
8′-OCH3 | 56.2, CH3 | 56.3, CH3 | 56.2, CH3 |
SW620 Ad300 | ||||
---|---|---|---|---|
Treatment | IC50 (μM) | FR | GS | FI |
doxorubicin | 5.75 | 57.5 | 1.0 | 0.12 |
verapamil | >30 | ND | ND | - |
+ verapamil (2.5 μM) | 0.71 | 7.1 | 8.1 | 1.00 |
+ chrysosporazine T (1) | 0.97 | 9.7 | 5.9 | 0.61 |
+ chrysosporazine C (9) | 0.31 | 3.1 | 18.5 | 2.28 |
+ chrysosporazine U (2) | 2.76 | 27.6 | 2.0 | 0.25 |
+ chrysosporazine D (7) | 4.36 | 43.6 | 1.32 | 0.16 |
+ azachrysosporazine T1 (3) | 0.89 | 8.9 | 6.4 | 0.80 |
+ azachrysosporazine C1 (11) | 0.27 | 2.7 | 21.3 | 2.63 |
+ azachrysosporazine U1 (4) | 2.78 | 27.8 | 2.0 | 0.25 |
+ azachrysosporazine D1 (12) | 3.55 | 35.5 | 1.6 | 0.20 |
+ neochrysosporazine R (5) | 0.58 | 5.8 | 9.9 | 1.22 |
+ neochrysosporazine I (13) | 1.01 | 10.1 | 5.7 | 0.70 |
+ neochrysosporazine S (6) | 1.95 | 19.5 | 2.9 | 0.36 |
+ neochrysosporazine J (14) | 6.18 | 61.8 | 0.9 | 0.11 |
+ brasiliamide A (8) | 5.27 | 52.7 | 1.1 | 0.13 |
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Agampodi Dewa, A.; Khalil, Z.G.; Elbanna, A.H.; Capon, R.J. Chrysosporazines Revisited: Regioisomeric Phenylpropanoid Piperazine P-Glycoprotein Inhibitors from Australian Marine Fish-Derived Fungi. Molecules 2022, 27, 3172. https://doi.org/10.3390/molecules27103172
Agampodi Dewa A, Khalil ZG, Elbanna AH, Capon RJ. Chrysosporazines Revisited: Regioisomeric Phenylpropanoid Piperazine P-Glycoprotein Inhibitors from Australian Marine Fish-Derived Fungi. Molecules. 2022; 27(10):3172. https://doi.org/10.3390/molecules27103172
Chicago/Turabian StyleAgampodi Dewa, Amila, Zeinab G. Khalil, Ahmed H. Elbanna, and Robert J. Capon. 2022. "Chrysosporazines Revisited: Regioisomeric Phenylpropanoid Piperazine P-Glycoprotein Inhibitors from Australian Marine Fish-Derived Fungi" Molecules 27, no. 10: 3172. https://doi.org/10.3390/molecules27103172
APA StyleAgampodi Dewa, A., Khalil, Z. G., Elbanna, A. H., & Capon, R. J. (2022). Chrysosporazines Revisited: Regioisomeric Phenylpropanoid Piperazine P-Glycoprotein Inhibitors from Australian Marine Fish-Derived Fungi. Molecules, 27(10), 3172. https://doi.org/10.3390/molecules27103172