Antibacterial Indole Diketopiperazine Alkaloids from the Deep-Sea Cold Seep-Derived Fungus Aspergillus chevalieri
Abstract
:1. Introduction
2. Results and Discussion
2.1. Structure Elucidation
2.2. Antimicrobial Activity
3. Experimental Section
3.1. General Experimental Procedures
3.2. Fungal Material
3.3. Fermentation, Extraction, and Isolation
- 24,25-Dihydroxyvariecolorin G (1): colorless amorphous powder; [α]25 D –17.4 (c =0.23, MeOH); UV (MeOH) λmax (log ε) 226 (3.26) nm, 252 (3.11) nm, 279 (2.90) nm, 335 (2.96) nm; ECD (0.35 mM, MeOH) λmax (Δε) 214 (–5.52), 240 (+2.22), 342 (–1.46) nm; 1H and 13C NMR data, Table 1 and Table 2; HRESIMS m/z 424.2225 [M+H]+ (calcd for C24H30N3O4, 424.2231).
- 25-Hydroxyrubrumazine B (2): colorless amorphous powder; [α]25 D –23.8 (c =0.21, MeOH); UV (MeOH) λmax (log ε) 225 (3.66) nm, 255 (3.28) nm, 282 (3.13) nm, 339 (3.22) nm; ECD (0.57 mM, MeOH) λmax (Δε) 221 (–11.88), 248 (+0.52), 333 (–1.97) nm; 1H and 13C NMR data, Table 1 and Table 2; HRESIMS m/z 442.2330 [M+H]+ (calcd for C24H32N3O5, 442.2336).
- 22-Chloro-25-hydroxyrubrumazine B (3): colorless amorphous powder; [α]25 D –25.0 (c =0.16, MeOH); UV (MeOH) λmax (log ε) 224 (3.56) nm, 257 (3.15) nm, 278 (2.98) nm, 335 (3.06) nm; ECD (0.35 mM, MeOH) λmax (Δε) 206 (–9.54), 234 (+7.56), 328 (–3.46) nm; 1H and 13C NMR data, Table 1 and Table 2; HRESIMS m/z 460.1987 [M+H]+ (calcd for C24H30ClN3O4, 460.1998).
- 25-Hydroxyvariecolorin F (4): colorless amorphous powder; [α]25 D –53.8 (c =0.26, MeOH); UV (MeOH) λmax (log ε) 226 (3.70) nm, 255 (3.30) nm, 279 (3.13) nm, 334 (3.22) nm; ECD (0.28 mM, MeOH) λmax (Δε) 204 (–12.69), 240 (+2.38), 334 (–2.71) nm; 1H and 13C NMR data, Table 1 and Table 2; HRESIMS m/z 460.1992 [M+H]+ (calcd for C24H30ClN3O4, 460.1998).
- 27-epi-Aspechinulin D (5): colorless amorphous powder; [α]25 D –23.1 (c =0.13, MeOH); UV (MeOH) λmax (log ε) 231 (3.61) nm, 280 (2.99) nm; ECD (0.26 mM, MeOH) λmax (Δε) 226 (–9.63), 271 (+1.03) nm; 1H and 13C NMR data, Table 1 and Table 2; HRESIMS m/z 496.3157 [M+H]+ (calcd for C29H42N3O4, 496.3170).
3.4. Computational NMR Chemical Shift Calculation and DP4+ Analysis
3.5. Acidic Hydrolysis of Compounds 1–5
3.6. 2,2-Dimethoxypropane Derivatization of Compound 4
3.7. Antibacterial Assay
3.8. Scanning Electron Microscopy (SEM)
4. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Acknowledgments
Conflicts of Interest
References
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No. | 1 | 2 | 3 | 4 | 5 |
---|---|---|---|---|---|
1-NH | 10.58, s | 10.46, s | 10.13, s | 10.10, s | 9.89, s |
4 | 7.04, dd, (7.4, 1.7) | 7.05, m | 7.09, m | 7.08, dd, (7.3, 1.7) | 7.07, s |
5 | 6.96, t, (7.4) | 6.94, overlap | 6.99, overlap | 6.98, overlap | |
6 | 6.93, dd, (7.4, 1.7) | 6.94, overlap | 7.00, overlap | 7.00, overlap | 6.71, s |
8 | 6.88, s | 6.90, s | 6.88, s | 6.89, s | Ha, 3.01, dd, (14.5, 9.6) Hb, 3.34, m |
9 | 3.96, m | ||||
11-NH | 8.31, s | 8.31, s | 8.33, s | 8.34, s | 8.18, s |
12 | 4.15, qd, (6.9, 1.6) | 4.16, q, (6.9) | 4.14, qd, (6.9, 1.4) | 4.17, qd, (6.9, 1.9) | 3.82, qd, (6.9, 2.3) |
14-NH | 8.62, s | 8.56, s | 8.74, s | 8.57, s | 7.41, s |
16 | 6.10, dd, (17.6, 10.3) | 6.09, dd, (17.3, 10.6) | 6.11, dd, (17.2, 10.6) | 6.10, dd, (17.3, 10.6) | 6.16, dd, (17.4, 10.6) |
17 | Ha, 5.03, dd, (17.6, 1.3) Hb, 5.03, dd, (10.3, 1.3) | Ha, 5.05, dd, (17.3, 1.2) Hb, 5.06, dd, (10.6, 1.2) | Ha, 5.04, d, (17.2) Hb, 5.05, d, (10.6) | Ha, 5.06, dd, (17.3, 1.2) Hb, 5.07, dd, (10.6, 1.2) | Ha, 5.08, d, (17.4) Hb, 5.04, d, (10.6) |
18 | 1.48, s | 1.49, s | 1.50, s | 1.50, s | 1.48, s |
19 | 1.48, s | 1.49, s | 1.50, s | 1.50, s | 1.49, s |
20 | 1.37, d, (6.9) | 1.37, d, (6.9) | 1.39, d, (6.9) | 1.38, d, (6.9) | 1.33, d, (6.9) |
21 | 3.76, d, (7.8) | Ha, 2.76, dd, (14.6, 8.8) Hb, 3.25, d, (14.6) | Ha, 3.15, dd, (15.5, 10.6) Hb, 3.67, d, (15.5) | Ha, 2.93, dd, (14.6, 8.8) Hb, 3.31, d, (14.6) | 3.31, d, (7.2) |
22 | 5.59, t, (7.8) | 3.70, d, (8.8) | 4.37, d, (10.6) | 3.97, t, (8.8) | 5.32, t, (7.2) |
22-OH | 5.31, d, (7.2) | ||||
23-OH | 5.14, s | ||||
24 | 3.96, d, (4.2) | 1.12, s | 1.28, s | 1.56, s | 1.71, s |
24-OH | 4.70, t, (4.2) | ||||
25 | 4.19, d, (3.8) | Ha, 3.46, d, (10.9) Hb, 3.40, d, (10.9) | 3.57, m | 3.75, m | 1.70, s |
25-OH | 5.32, t, (3.8) | 5.26, t, (5.5) | 5.54, t, (6.1) | ||
26 | Ha, 2.65, dd, (14.5, 8.7) Hb, 3,13, d, (14.5) | ||||
27 | 3.42, m | ||||
27-OH | 4.99, d, (5.7) | ||||
28-OH | 4.69, s | ||||
29 | 1.16, s | ||||
30 | 1.17, s |
No. | 1 | 2 | 3 | 4 | 5 |
---|---|---|---|---|---|
2 | 143.8, C | 143.5, C | 143.6, C | 143.5, C | 141.0, C |
3 | 103.9, C | 103.8, C | 104.2, C | 104.0, C | 104.9, C |
3a | 126.0, C | 125.9, C | 126.1, C | 126.0, C | 129.1, C |
4 | 117.0, CH | 116.8, CH | 117.3, CH | 117.0, CH | 114.8, CH |
5 | 121.1, CH | 119.6, CH | 119.5, CH | 119.7, CH | 131.4, C |
6 | 119.7, CH | 121.7, CH | 121.3, CH | 121.9, CH | 122.2, CH |
7 | 123.7, C | 125.2, C | 122.6, C | 123.8, C | 124.1, C |
7a | 133.9, C | 134.3, C | 133.9, C | 134.2, C | 132.7, C |
8 | 110.3, CH | 110.2, CH | 110.1, CH | 110.0, CH | 31.3, CH2 |
9 | 125.1, C | 124.8, C | 125.2, C | 125.1, C | 55.6, CH |
10 | 159.9, C | 159.9, C | 159.8, C | 159.8, C | 167.4, C |
12 | 50.5, CH | 50.5, CH | 50.6, CH | 50.5, CH | 50.3, CH |
13 | 166.4, C | 166.3, C | 166.4, C | 166.4, C | 167.9, C |
15 | 39.1, C | 38.9, C | 39.0, C | 38.9, C | 38.7, C |
16 | 145.4, CH | 145.1, CH | 145.2, CH | 145.1, CH | 146.5, CH |
17 | 111.4, CH2 | 111.7, CH2 | 111.7, CH2 | 111.8, CH2 | 111.1, CH2 |
18 | 27.6, CH3 | 27.4, CH3 | 27.6, CH3 | 27.5, CH3 | 27.9, CH3 |
19 | 27.6, CH3 | 27.4, CH3 | 27.5, CH3 | 27.4, CH3 | 27.9, CH3 |
20 | 19.6, CH3 | 19.6, CH3 | 19.8, CH3 | 19.6, CH3 | 20.7, CH3 |
21 | 29.6, CH2 | 34.0, CH2 | 33.8, CH2 | 34.2, CH2 | 34.2, CH2 |
22 | 124.7, CH | 74.8, CH | 66.9, CH | 77.7, CH | 124.9, CH |
23 | 139.2, C | 74.2, C | 74.2, C | 74.0, C | 130.2, C |
24 | 63.5, CH2 | 19.1, CH3 | 21.0, CH3 | 22.8, CH3 | 17.7, CH3 |
25 | 57.1, CH2 | 67.6, CH2 | 67.5, CH2 | 68.1, CH2 | 25.6, CH3 |
26 | 34.5, CH2 | ||||
27 | 79.0, CH | ||||
28 | 72.2, C | ||||
29 | 23.6, CH3 | ||||
30 | 27.0, CH3 |
Strain | Compound | ||||||
---|---|---|---|---|---|---|---|
1 | 2 | 3 | 4 | 5 | 6 | Chloramphenicol b | |
Vibrio harveyi | 16 | 32 | 8 | 32 | 16 | - | 2 |
Edwardsiella tarda | -a | 16 | - | - | 32 | - | 8 |
Aeromonas hydrophila | - | 32 | - | - | 32 | 4 | 2 |
Escherichia coli | 4 | 16 | 32 | 32 | 32 | 8 | 2 |
Micrococcus luteus | - | 32 | - | - | 16 | - | 2 |
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Yan, L.-H.; Du, F.-Y.; Li, X.-M.; Yang, S.-Q.; Wang, B.-G.; Li, X. Antibacterial Indole Diketopiperazine Alkaloids from the Deep-Sea Cold Seep-Derived Fungus Aspergillus chevalieri. Mar. Drugs 2023, 21, 195. https://doi.org/10.3390/md21030195
Yan L-H, Du F-Y, Li X-M, Yang S-Q, Wang B-G, Li X. Antibacterial Indole Diketopiperazine Alkaloids from the Deep-Sea Cold Seep-Derived Fungus Aspergillus chevalieri. Marine Drugs. 2023; 21(3):195. https://doi.org/10.3390/md21030195
Chicago/Turabian StyleYan, Li-Hong, Feng-Yu Du, Xiao-Ming Li, Sui-Qun Yang, Bin-Gui Wang, and Xin Li. 2023. "Antibacterial Indole Diketopiperazine Alkaloids from the Deep-Sea Cold Seep-Derived Fungus Aspergillus chevalieri" Marine Drugs 21, no. 3: 195. https://doi.org/10.3390/md21030195