Antiparasitic Ovalicin Derivatives from Pseudallescheria boydii, a Mutualistic Fungus of French Guiana Termites
Abstract
:1. Introduction
2. Results
3. Materials and Methods
3.1. General Experimental Procedures
3.2. Collection and Identification of Pseudallescheria boydii
3.3. Culture, Extraction, and Isolation
3.4. Fatty Acid Methyl Ester Synthesis from Ovalicin Linoleate (2) and Ovalicin Oleate (3)
3.4.1. Hydrolysis
3.4.2. Esterification
3.5. Semisynthesis of Ovalicin Linoleate, Ovalicin Oleate, and Ovalicin Stearate
3.5.1. Synthesis of Ovalicin Linoleate (2b)
3.5.2. Synthesis of Ovalicin Oleate (3b)
3.5.3. Synthesis of Ovalicin Stearate (4b)
3.6. Identification of the Double-Bond Position in Fatty Acid Methyl Esters by Liquid Chromatography/Atmospheric Pressure Chemical Ionization Mass Spectrometry
3.7. Metabolomic Profiling and Molecular Network Analysis
3.7.1. LC–MS/MS and Data Analysis
3.7.2. Data Processing and Analysis
3.8. Genomic Analyses
3.8.1. gDNA Extraction of P. boydii Strains SNB-CN71, -CN73, -CN81, and -CN85
3.8.2. Whole Genome Sequencing and Hybrid Assembly
3.9. Biological Tests
3.9.1. Antimicrobial Assays
3.9.2. Antiparasitic Activities
Assay for In Vitro Inhibition of T. brucei brucei Growth
In Vitro Growth Inhibition of Chloroquine-Resistant P. falciparum
3.9.3. Cytotoxic 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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N° | 2 | 3 | 4 | 5 | 6 | ||||
---|---|---|---|---|---|---|---|---|---|
Pos. | δc, Type | δH (J in Hz) | δc | δH | δc | δH | δH | δc | δH |
1 | 211.1, C | 211.1, C | 211.2, C | 211.6, C | |||||
2 | 36.5, CH2 | 2.74, m | 36.5, CH2 | 2.74, bsex (7.3) | 36.5, CH2 | 2.74, td (13.7; 7.6) | 2.74, m | 36.5, CH2 | 2.76, m |
2.22, m | 2.22, m | 2.23, m | 2.22, m | 2.29, m | |||||
3 | 32.8, CH2 | 2.10, dd (13.6, 5.1) | 32.7, CH2 | 2.09, m | 32.8, CH2 | 2.09, td (13.6; 7.1) | 2.09, m | 32.8, CH2 | 2.12, m |
2.01, ddd (13.6, 7.1, 2.0) | 2.01, m | 2.01, ddd (13.6; 7.1; 1.9) | 2.01, m | 2.04, m | |||||
4 | 76.5, C | 76.5, C | 76.5 *, C | 76.3 *, C | |||||
5 | 82.8, C | 82.7, C | 82.8, C | 81.8 *, C | |||||
6 | 62.8, C | 62.7 *, C | 62.7 *, C | 62.3 *, C | |||||
7 | 86.2, CH | 4.69, s | 86.2, CH | 4.69, s | 86.2, CH | 4.69, s | 4.69, s | 77.5, CH | 5.02, s |
8 | 58.4, CH | 2.97, t (6.5) | 58.3, CH | 2.97, t (6.5) | 58.4, CH | 2.97, t (6.5) | 2.97, t (6.5) | 57.9 *, CH | 2.96, t (6.8) |
9 | 28.4, CH2 | 2.38, m | 28.4, CH2 | 2.37, m | 28.4, CH2 | 2.38, m | 2.37, m | 28.4, CH2 | 2.38, m |
2.26, m | 2.27, m | 2.25, m | 2.26, m | 2.26, m | |||||
10 | 119.8, CH | 5.28, m | 119.8, CH | 5.27, m | 119.8, CH | 5.27, m | 5.27, m | 119.9, CH | 5.28, m |
11 | 136.1, C | 136.1, C | 136.1, C | 136.0, C | |||||
12 | 26.1, CH3 | 1.72, brd (1.2) | 26.1, CH3 | 1.73, bd (1.1) | 26.0, CH3 | 1.73, bs | 1.73, bd (1.2) | 26.1, CH3 | 1.72, bs |
13 | 18.2, CH3 | 1.68, brd (0.9) | 18.2, CH3 | 1.68, bd (0.8) | 18.2, CH3 | 1.68, bs | 1.68, bd (0.8) | 18.2, CH3 | 1.68, bs |
14 | 69.4, CH2 | 4.17, d (11.2) | 69.4, CH2 | 4.17, d (11.1) | 69.4, CH2 | 4.17, d (11.1) | 4.17, d (11.1) | 69.5, CH2 | 4.18, d (11.1) |
4.11, d (11.2) | 4.11, d (11.1) | 4.11, d (11.1) | 4.11, d (11.1) | 4.12, d (11.1) | |||||
15 | 16.3, CH3 | 1.54, s | 16.3, CH3 | 1.55, s | 16.3, CH3 | 1.54, s | 1.55, s | 16.3, CH3 | 1.61, s |
OMe | 59.7, CH3 | 3.49, s | 59.7, CH3 | 3.49, s | 59.7, CH3 | 3.48, s | 3.49, s | 175.2, C | |
1′ | 175.5, C | 175.4, C | 175.5, C | 35.1, CH2 | 2.38, m | ||||
2′ | 35.1, CH2 | 2.38, t (7.4) | 35.1, CH2 | 2.38, m | 35.1, CH2 | 2.38, m | 2.38, m | 26.2, CH2 | 1.64, m |
3′ | 26.2, CH2 | 1.64, m | 26.1, CH2 | 1.64, m | 26.4, CH2 | 1.25–1.37, m | 1.64, m | 30.2–30.8, CH2 | 1.27–1.40, m |
4′–7′ | 30.3−30.8, CH2 | 1.28, m–1.40, m | 30.2–31.0, CH2 | 1.26–1.40, m | 30.3–31.0, CH2 | 1.25–1.37, m | 1.25–1.40, m | 30.4, CH2 | 1.37, m |
8′ | 28.3, CH2 | 2.07, m | 28.3, CH2 | 2.03, m | 33.2, CH2 | 1.25–1.37, m | 2.03, m | 28.4, CH2 | 2.07, m |
9′ | 131.0, CH | 5.36, m | 130.9, CH | 5.35, m | 23.9, CH2 | 1.25–1.37, m | 5.35, m | 131.0, CH | 5.36, m |
10′ | 129.3, CH | 5.33, m | 131.1, CH | 5.35, m | 14.6, CH3 | 1.25–1.37, m | 5.35, m | 129.3, CH | 5.33, m |
11′ | 26.7, CH2 | 2.78, m | 28.3, CH2 | 2.03, m | 211.2, C | 1.25–1.37, m | 2.03, m | 26.7, CH2 | 2.77, m |
12′ | 129.2, CH | 5.33, m | 30.2–31.0, CH2 | 1.26–1.40, m | 36.5, CH2 | 1.25–1.37, m | 1.26–1.40, m | 129.2, CH | 5.33, m |
13′ | 131.1, CH | 5.36, m | 30.2–1.0, CH2 | 1.26–1.40, m | 1.25–1.37, m | 1.30, m | 131.1, CH | 5.36, m | |
14′ | 28.3, CH2 | 2.07, m | 30.2–31.0, CH2 | 1.26–1.40, m | 32.8, CH2 | 1.25–1.37, m | 1.29, m | 28.4, CH2 | 2.07, m |
15′ | 30.3–30.8, CH2 | 1.28, m–1.40, m | 30.2–31.0, CH2 | 1.26–1.40, m | 1.25–1.37, m | 0.90, t (7.0) | 30.4, CH2 | 1.37, m | |
16′ | 32.8, CH2 | 1.31, m | 33.2, CH2 | 1.30, m | 76.5 *, C | 1.29, m | 32.8, CH2 | 1.31, m | |
17′ | 23.8, CH2 | 1.34, m | 23.9, CH2 | 1.29, m | 82.8, C | 1.29, m | 23.8, CH2 | 1.33, m | |
18′ | 14.6, CH3 | 0.91, t (7.0) | 14.6, CH3 | 0.90, t (7.0) | 62.7 *, C | 0.90, t (7.0) | 14.6 | 0.91, t (7.2) |
Cmpd. | P. falciparum (IC50 µM) | T. brucei brucei (IC50 µM) | HUVECs (IC50 µM) |
---|---|---|---|
1 | 13.6 ± 6.4 | 0.41 ± 0.17 | 13 ± 2 |
2 | 19.8 ± 6.7 | 1.1 ± 0.5 | 37 ± 3 |
3 | >50 | 4.8 ± 2.7 | 45 ± 2 |
4 | 20.6 ± 4.6 | 4.1 ± 2.1 | 70 ± 1 |
Position | δC, Type | δH (J in Hz) |
---|---|---|
1 | 178.0, C | |
2 | 29.3, CH2 | 2.22 |
3 | 25.6, CH2 | 2.27, m |
2.05, m | ||
4 | 61.5, C | |
5 | 76.0, C | |
6 | 63.4, C | |
7 | 63.6, CH2 | 3.64, d (11.6) |
3.60, d (11.6) | ||
8 | 58.3, CH | 3.26, t (6.5) |
9 | 28.0, CH2 | 2.36, m |
2.22, m | ||
10 | 119.8, C | 5.24, m |
11 | 135.4, C | |
12 | 25.8, CH3 | 1.67, s |
13 | 17.9, CH3 | 1.73, s |
14 | 48.8 | 3.00, d (3.9) |
2.68, d (3.9) | ||
15 | 17.6, CH3 | 1.37, s |
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Sorres, J.; Hebra, T.; Elie, N.; Leman-Loubière, C.; Grayfer, T.; Grellier, P.; Touboul, D.; Stien, D.; Eparvier, V. Antiparasitic Ovalicin Derivatives from Pseudallescheria boydii, a Mutualistic Fungus of French Guiana Termites. Molecules 2022, 27, 1182. https://doi.org/10.3390/molecules27041182
Sorres J, Hebra T, Elie N, Leman-Loubière C, Grayfer T, Grellier P, Touboul D, Stien D, Eparvier V. Antiparasitic Ovalicin Derivatives from Pseudallescheria boydii, a Mutualistic Fungus of French Guiana Termites. Molecules. 2022; 27(4):1182. https://doi.org/10.3390/molecules27041182
Chicago/Turabian StyleSorres, Jonathan, Téo Hebra, Nicolas Elie, Charlotte Leman-Loubière, Tatyana Grayfer, Philippe Grellier, David Touboul, Didier Stien, and Véronique Eparvier. 2022. "Antiparasitic Ovalicin Derivatives from Pseudallescheria boydii, a Mutualistic Fungus of French Guiana Termites" Molecules 27, no. 4: 1182. https://doi.org/10.3390/molecules27041182