Identification of Bioactive Metabolites of Capirona macrophylla by Metabolomic Analysis, Molecular Docking, and In Vitro Antiparasitic Assays
Abstract
:1. Introduction
2. Materials and Methods
2.1. Plant Material
2.2. Extraction
2.3. Analysis by UHPLC/HRMSn
2.4. HPLC Fractionation
2.5. Metabolomic Analysis
2.6. Virtual Screening by Molecular Docking
2.7. Molecular Dynamics
2.8. In Vitro Biological Activity
2.8.1. Antiplasmodial Activity
2.8.2. Antileishmanial Activity
(fluorescence of control with no treatment − fluorescence of Medium RPMI)
2.8.3. Hemolysis Assay
3. Results and Discussion
3.1. Untargeted Metabolomic Analysis
3.2. Virtual Screening by Molecular Docking
3.3. Molecular Dynamics Simulations
3.4. Biological Activity
4. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
CID | PubChem Compound Identification |
CQA | Caffeoylquinic Acid |
D.E. | Docking Energy |
DHODH | Dihydroorotate Dehydrogenase enzyme |
DiCQA | Di Caffeoylquinic Acid |
HESI | Heated Electrospray Ionization |
GNPS | Global Natural Products Social Molecular Networking |
HPLC | High Performance Liquid Chromatography |
IC50 | Half maximal inhibitory concentration |
MeOH | Methanol |
ORO | Orotate substrate |
SisGen | Brazilian National System of Genetic Heritage Management and Associated Traditional Knowledge |
UHPLC/HRMSn | Ultra High-Performance Liquid Chromatography/High Resolution Tandem Mass Spectrometry |
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ID | tR (min) Average | Formula [M + H]+ | Experimental Mass (m/z) | Error (ppm) | Peak Area Leaf/Stem/Wood Bark | Name | CID PubChem | MS2 Ions and Percentages (m/z, %) |
---|---|---|---|---|---|---|---|---|
1 | 0.5 | - | 254.1606 | - | 9.2 × 106/1.5 × 108/8.8 × 108 | Unknown | - | 254.1609 (100%), 237.1342 (3.5%), 196.1163 (3.3%), and 195.1127 (32.0%) |
2 | 1.09 | C11H13N2O2 | 205.0971 | −2.75 | 1.7 × 108/1.7 × 108/3.8 × 108 | Tryptophan | 6305 | 188.0705 (100%), 146.06 (32.7%), 189.0740 (13.0%), 144.0807 (5.4%) and 159.0916 (5.3%) |
3 | 2.62 | C16H19O9 | 355.1026 | −0.96 | 1.6 × 108/2 × 108/4.6 × 108 | Chlorogenic acid | 1794427 | 163.0389 (100%), and 355.1026 (44.9%) |
4 | 2.87 | - | 289.1182 | - | 2.3 × 106/1.1 × 107/3 × 107 | Unknown | - | 216.1017 (100%), 272.0914 (53.7%), 289.1182 (44.9%), 188.0706 (20.5%) and 180.0803 (7.7%) |
5 | 3.29 | C30H27O12 | 579.1484 | −3.24 | 3 × 107/9.8 × 103/0 | Procyanidin | 130556 | 127.0389 (100%), 579.1385 (88.9%), 291.0858 (78.8%), 427.1019 (78.7%), and 409.0906 (55.3%) |
6 | 3.72 | - | 496.2035 | - | 8.2 × 105/8.7 × 106/8.6 × 107 | Unknown | - | 185.0808 (100%), 308.8935 (44.1%), 371.3235 (42.4%), and 330.3095 (37.6%) |
7 | 3.83 | C15H15O6 | 291.0855 | −4.55 | 5.5 × 107/7 × 105/5.5 × 104 | Epicatechin | 72276 | 139.0388 (100%), 123.0440 (52.5%), 291.0857 (28.8%), 165.0544 (26.2%), and 147.0438 (55.3%) |
8 | 4.46 | C24H15N2O5 | 291.0974 | −2.36 | 2.4 × 106/1.5 × 108/1.5 × 108 | Malonyltryptophan | 5199636 | 188.0867 (100%), 245.0919 (91.2%), 130.0652 (40.7%), 227.0814 (27.9%), 273.0867 (18.6%), and 291.0979 (17.4%) |
9 | 4.78 | C10H9O4 | 193.0497 | −2.1 | 1.9 × 107/4.5 × 108/3.3 × 108 | Scopoletin | 5280460 | 193.0495 (100%), 194.0528 (10.6%), 133.0284 (4.4%), and 178.0260 (1.9%) |
10 | 5.07/5.42 | C11H11O5 | 223.0597 | −4.48 | 4.4 × 106/5.3 × 108/6 × 107/1.2 × 106/1.3 × 108/1.2 × 107 | Isofraxidin | 5318565 | 223.0599 (100%), 224.0631 (11.2%), 208.0363 (4.6%), and 163.0387 (2.3%) |
11 | 5.13 | C11H17O3 | 197.1170 | −4.11 | 1.4 × 108/3.3 × 107/1.1 × 107 | Loliolide | 14334 | 197.1169 (100%), 179.1064 (83.7%), 135.1167 (44.4%), 104.0857 (19.9%), and 161.0958 (18.7%) |
12 | 5.89 | C28H35N2O11 | 575.2247 | 1.01 | 7.7 × 106/1 × 108/1.9 × 108 | 5-Carboxystrictosidine | 10483216 | 575.2227 (100%), 413.1701 (32.6%), 188.0704 (14%), 395.1589 (8.4%), and 165. 0811 (7.3%) |
13 | 7.32 | - | 181.1223 | - | 2.8 × 107/5.8 × 106/5.2 × 106 | Unknown | - | 181.1221 (100%), 135.1167 (15.4%), 163.1115 (13.5%), 139.0752 (4.1), 121.1012 (4.1%), and 95.0858 (3.76) |
14 | 8.30 | - | 367.1180 | - | 1.2 × 104/2.9 × 107/4.9 × 106 | Unknown | - | 367.1172 (100%), 336.0986 (54.3%), 337.1018 (7.9%), 321.0753 (1.4%), and 352.0924 (1.1%) |
15 | 10.08 | - | 335.2184 | - | 1.6 × 106/4 × 107/7.6 × 107 | Unknown | - | 335.2193 (100%), 195.0990 (0.3%), 71.17 (0.2%), and 203.3772 (0.1%) |
16 | 10.79 | C18H31O2 | 279.2315 | −3.31 | 1.7 × 106/2.7 × 107/7.3 × 107 | Linolenic acid | 5280934 | 279.2315 (100%), 95.0859 (44.1%), 81.0704 (43.9%), 67.0548 (26.7%), 109.1014 (23.5%), and 123.1169 (20.8%) |
ID | tR (min) Average | Formula [M-H]− | Experimental Mass m/z | Error (ppm) | Peak Area Leaf/Stem/Wood Bark | Name | CID PubChem | MS2 Ions and Percentages (m/z, %) |
---|---|---|---|---|---|---|---|---|
1 | 0.28 2.63 | C7H11O6 | 191.0551 | −2.54 | 5.9 × 107/7.3 × 107/1.5 × 108/5.4 × 108/1.3 × 109/1.2 × 109 | Quinic acid | 6508 | 191.0546 (100%), 85.0278 (2.5%), 173.0440 (0.9%), 127.0385 (0.9%) and 93.0329 (0.7%) |
2 | 1.08 | C16H17O9 | 353.0870 | −0.62 | 6 × 107/7.3 × 107/2.4 × 108 | 5-O-CQA * | 5280633 | 353.0867 (100%), 191.0546 (72.3%), 179.0334 (49.2%) and 135.0434 (8.03%) |
3 | 2.63 | C16H17O9 | 353.0873 | 0.06 | 1.4 × 108/1.8 × 108/3.7 × 108 | 3-O-CQA * | 1794427 | 191.0545 (100%), 353.0864 (19.9%), 179.0337 (4.5%), 192.0579 (3.5%) and 161.7553 (1%) |
4 | 2.90 | C16H17O9 | 353.0867 | −1.5 | 7.1 × 107/7.9 × 107/2.2 × 108 | 4-O-CQA * | 9798666 | 173.0438 (100%), 353.0864 (89.8%), 179.0333 (68.3%), 191.0545 (39%) and 135.0434 (13.5%) |
5 | 3.30 | C30H25O12 | 577.1356 | 1.76 | 3.1 × 107/3 × 103/2.1 × 103 | Procyanidin B2 | 122738 | 577.1346 (100%), 425.0876 (50.1%), 289.0715 (40.8%), 407.0769 (37.4%) and 125.0230 (33%) |
6 | 3.85 | C15H13O6 | 289.0716 | −0.81 | 3.6 × 107/4.1 × 104/5.5 × 103 | Epicatechin | 1203 | 289.0715 (100%), 245.0813 (20.3%), 125.0229 (5.6%), 205.0496 (5.5%) and 179.0339 (5%) |
7 | 4.48 | C13H13N2O3 | 245.0923 | −1.42 | 1.7 × 107/6.2 × 107/6.8 × 107 | N-Acetyltryptophan | 2002 | 245.0921 (100%), 203.0811 (64%), 74.0231 (27.3%) and 201.1022 (8.1%) |
8 | 4.56 | C17H19O9 | 367.1026 | −0.84 | 1.8 × 107/2.2 × 107/6.1 × 107 | 3-O-Feruloylquinic acid | 9799386 | 173.0443 (100%), 191.0546 (76.7%), 367.1020 (50%), 193.0491 (18.7%) and 93.0329 (7%) |
9 | 5.22 | - | 581.2208 | - | 5.6 × 104/7.8 × 105/8.3 × 106 | Unknown | - | 581.2225 (100%), 419.1700 (12.9%), 101.0227 (4.3%), 153.0542 (3.3%) |
10 | 5.41 | C26H27O16 | 595.1309 | 1.69 | 8.4 × 106/4.8 × 105/1 × 104 | Quercetin-3-O-vicianoside | 13887800 | 595.1301 (100%), 300.0271 (52.2%), 301.0329 (10.9%), 178.9975 (0.9%) and 302.0391 (0.6%) |
11 | 5.74 | C25H23O12 | 515.1192 | 0.48 | 2.5 × 107/1.6 × 107/9.1 × 106 | 1,5-DiCQA ** | 122685 | 515.1188 (100%), 353.0874 (60%), 179.0338 (32.3%), 173.0443 (25.3%) and 191.0550 (24.9%) |
12 | 5.89 | C27H29O16 | 609.1456 | 0.11 | 2.4 × 107/8.6 × 105/2.2 × 105 | Quercetin-3-O-rutinose | 5293655 | 609.1452 (100%), 300.0271 (32.8%), 301.0343 (32.8%), 67.4327 (2.4%) and 302.0387 (1.1%) |
13 | 6.19 | C25H23O12 | 515.1193 | 0.71 | 2.2 × 107/8.7 × 106/3.5 × 106 | 3,4-DiCQA ** | 3802778 | 515.1189 (100%), 353.0874 (72.1%), 173.0443 (41.8%), 179.0338 (29.2%) and 191.0549 (9.4%) |
14 | 6.27 | - | 187.0964 | - | 3.6 × 106/2.4 × 107/6.8 × 107 | Unknown | - | 125.0957 (100%), 126.0991 (5.4%), 169.0857 (5.0%) and 143.1065 (1.8%) |
15 | 6.30 | C33H39O19 | 739.2066 | −2.65 | 4.8 × 105/2.2 × 106/3.7 × 106 | Kaempferol-3-O-robinoside-7-O-rhamnoside | 5351997 | 739.2043 (100%), 577.1774 (75.3%), 173.0442 (30.2%), 578.1737 (21.1%) 191.0555 (20.3) |
16 | 6.91 | - | 241.1077 | - | 4.2 × 105/7.2 × 105/3.2 × 107 | Unknown | - | 241.1065 (100%), 197.1165 (74.5%), 67.5990 (6.8%) and 179.1060 (6.6%) |
17 | 7.25 | C10H17O4 | 201.1123 | −1.96 | 1.4 × 106/1.1 × 107/2.3 × 107 | Decanedioic acid | 5192 | 201.1118 (100%), 67.3854 (24.8%), 139.1109 (8.7%), 183.1008 (7.7%%) and 111.0799 (5.4%) |
18 | 8.80 | C18H33O5 | 329.2322 | −1.79 | 5.4 × 106/5.5 × 107/6.3 × 107 | FA 18:1 + 3O | 153001 | 329.2323 (100%), 171.1010 (6.6%), 211.1326 (4.6%), 229.1432 (3.86%) and 311.2209 (0.5%) |
19 | 10.08 | C18H31O4 | 311.2223 | 0.18 | 1.3 × 106/2.9 × 107/7.2 × 107 | FA 18:2 + 2O | 1928 | 311.2218 (100%), 171.1011 (24.9%), 293.2113 (10.9%), 185.1168 (5.9%) and 201.1118 (4.7%) |
20 | 10.79 | - | 295.2260 | - | 4.8 × 105/1.5 × 107/4.2 × 107 | Unknown | - | 183.1373 (100%), 277.2157 (71.4%), 68.0670 (20.5%) and 171.1007 (19.6%) |
DHODH Leishmania major | DHODH Plasmodium falciparum | ||||
---|---|---|---|---|---|
CID | Name | kcal/mol | CID | Name | kcal/mol |
5281780 | 3,4-Dicaffeoylquinic acid | −8.78 | 51347395 | DSM265 * | −9.82 |
1492348 | Orotate (ORO*) | −8.56 | 5280863 | Kaempferol | −8.82 |
9799386 | 3-Feruloylquinic acid | −8.35 | 5280343 | Quercetin | −8.62 |
12358846 | 1,4-Dicaffeoylquinic acid | −8.08 | 161313 | Anabasamine | −8.57 |
10466307 | Loganetin | −7.41 | 6476139 | Methyl chlorogenate | −7.78 |
6476139 | Methyl chlorogenate | −7.34 | 5282944 | 9-HODE | −7.59 |
14334 | Loliolide | −7.08 | 1794427 | 3-Caffeoylquinic acid | −7.5 |
1794427 | 3-O-Caffeoylquinic acid | −7.02 | 348159 | (-)-5-Caffeoylquinic acid | −7.43 |
348159 | (-)-5-Caffeoylquinic acid | −6.77 | 9799386 | 3-Feruloylquinic acid | −7.38 |
58427569 | 4-O-Caffeoylquinic acid | −6.67 | 14334 | Loliolide | −7.01 |
5280460 | Scopoletin | −6.58 | 10466307 | Loganetin | −6.99 |
5199636 | N-Malonyltryptophan | −6.54 | 5199636 | N-Malonyltryptophan | −6.95 |
23760099 | Diderroside | −6.51 | 101756906 | Diderroside methyl ester | −6.77 |
5280633 | 5-Caffeoylquinic acid | −6.28 | 58427569 | 4-Caffeoylquinic acid | −6.72 |
14158101 | 3-p-Coumaroylquinic acid | −6.18 | 5281780 | 3,4-Dicaffeoylquinic acid | −6.67 |
5280863 | Kaempferol | −6.16 | 1148 | DL-Tryptophan | −6.45 |
5280343 | Quercetin | −6.12 | 5460026 | beta-Gentiobiose | −5.66 |
161313 | Anabasamine | −5.98 | 12358846 | 1,4-Dicaffeoylquinic acid | −5.65 |
6508 | Quinic acid | −5.75 | 5429 | Theobromine | −5.59 |
1148 | DL-Tryptophan | −5.52 | 798 | Indole | −5.37 |
10483216 | 5(S)-5-Carboxystrictosidine | −5.51 | 23760099 | Diderroside | −5.07 |
101756906 | Diderroside methyl ester | −5.14 | 22563 | Desethylatrazine | −5.07 |
5282944 | 9-HODE | −5.06 | 998 | Phenylacetaldehyde | −4.9 |
5429 | Theobromine | −4.96 | 135398660 | Pterin | −4.69 |
5281769 | 1,5-Dicaffeoylqunic acid | −4.8 | 6508 | Quinic acid | −4.65 |
5460026 | beta-Gentiobiose | −4.69 | 75368781 | 4,5-Dycaffeoylquinic acid | −4.63 |
798 | Indole | −4.65 | 5281769 | 1,5-Dicaffeoylquinic acid | −3.10 |
998 | Phenylacetaldehyde | −4.51 | 10483216 | 5(S)-5-Carboxystrictosidine | −2.17 |
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Evaristo, J.; Laia, E.d.; Tavares, B.; Mendonça, E.; Grisostenes, L.; Rodrigues, C.; do Nascimento, W.; Garcia, C.; Guterres, S.; Nogueira, F.; et al. Identification of Bioactive Metabolites of Capirona macrophylla by Metabolomic Analysis, Molecular Docking, and In Vitro Antiparasitic Assays. Metabolites 2025, 15, 157. https://doi.org/10.3390/metabo15030157
Evaristo J, Laia Ed, Tavares B, Mendonça E, Grisostenes L, Rodrigues C, do Nascimento W, Garcia C, Guterres S, Nogueira F, et al. Identification of Bioactive Metabolites of Capirona macrophylla by Metabolomic Analysis, Molecular Docking, and In Vitro Antiparasitic Assays. Metabolites. 2025; 15(3):157. https://doi.org/10.3390/metabo15030157
Chicago/Turabian StyleEvaristo, Joseph, Elise de Laia, Bruna Tavares, Esdras Mendonça, Larissa Grisostenes, Caroline Rodrigues, Welington do Nascimento, Carolina Garcia, Sheila Guterres, Fábio Nogueira, and et al. 2025. "Identification of Bioactive Metabolites of Capirona macrophylla by Metabolomic Analysis, Molecular Docking, and In Vitro Antiparasitic Assays" Metabolites 15, no. 3: 157. https://doi.org/10.3390/metabo15030157
APA StyleEvaristo, J., Laia, E. d., Tavares, B., Mendonça, E., Grisostenes, L., Rodrigues, C., do Nascimento, W., Garcia, C., Guterres, S., Nogueira, F., Zanchi, F., & Evaristo, G. (2025). Identification of Bioactive Metabolites of Capirona macrophylla by Metabolomic Analysis, Molecular Docking, and In Vitro Antiparasitic Assays. Metabolites, 15(3), 157. https://doi.org/10.3390/metabo15030157