Iridoids from Himatanthus sucuuba Modulate Feeding Behavior of Lutzomyia longipalpis: Integrated Experimental and Computational Approaches
Abstract
1. Introduction
2. Results
2.1. Preparation of Crude Extract and Isolation of Iridoids
2.2. Survival Studies
2.3. Repellency Studies
2.4. Diet Preference Detection
2.5. Quantification of Sugar Intake
2.6. Acute Toxicity in Non-Target Organism: Drosophila melanogaster
2.7. Homology Modeling, Molecular Docking, and Molecular Dynamics Simulation
2.7.1. Homology Modeling and Quality Assessment
2.7.2. Molecular Docking—Gustatory Receptor A0A1B0CHD5
2.7.3. Simulation of the Molecular Dynamics of Ligand–GR Complexes
3. Discussion
3.1. Characterization and Biological Activity of Isolated Iridoids
3.2. Effects on Longevity and Feeding Behavior of L. longipalpis
3.3. Evaluation of the Repellent Potential of Iridoids
3.4. Diet Preference Studies: Temporal Exposure and Choice Behavior
3.5. Quantifying Sugar Intake: Dietary Patterns and Physiological Implications
3.6. Safety Assessment in Non-Target Organisms: Drosophila melanogaster Model
3.7. Homology Modeling, Molecular Docking, and Molecular Dynamics Simulation
4. Materials and Methods
4.1. Plant Material and Crude Extract Preparation
4.2. Fractionation of the Mixture Isoplumericin and Plumericin from the Dichloromethane Extract
4.3. Identification and Characterization of the Iridoids Isoplumericin and Plumericin
4.3.1. Gas Chromatography-Mass Spectrometry (GC-MS)
4.3.2. Nuclear Magnetic Resonance (NMR)
4.4. In Vivo Experiments
4.4.1. Insects
4.4.2. Lutzomyia longipalpis Longevity Curves
4.4.3. Repellency Tests on Sand Flies
4.4.4. Sugar Intake Experiments
- Short exposure (3 h)
- Continuous exposure (48 h)
4.4.5. Detection and Quantification of Sugars from Sugar Intake Experiments
4.4.6. Non-Target Organism Toxicity
4.5. In Silico Analysis
4.5.1. Sequence Retrieval and Homology Modeling
4.5.2. Model Quality Assessment
4.5.3. Selection and Construction of 3D Ligand Structures
4.5.4. Validation of Docking Protocol
4.5.5. Molecular Docking
4.5.6. Analysis of Intermolecular Interactions and Figure Construction
4.5.7. Molecular Dynamic Simulation
4.6. Statistical Analysis
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
CL | Cutaneous leishmaniasis |
MCL | Mucocutaneous leishmaniasis |
VL | Visceral leishmaniasis |
DMSO | Dimethyl sulfoxide |
GC-MS | Gas Chromatograph-Mass Spectrometer |
GR | Gustatory Receptor |
NMR | Nuclear Magnetic Resonance |
RMSD | Root Mean Square Deviation |
RMSF | Root Mean Square Fluctuation |
SR | Sugar receptor |
Appendix A
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Comparative | % Amino Acids in Ramachandran Plot Regions (PROCHECK) | PROSA | |||||
---|---|---|---|---|---|---|---|
Favorable | Allowed | Gen. allowed | Nonallowed | Qmean6 | Z-QMEAN | Z-score | |
SWISS-MODEL | 95.4 | 4.6 | 0.0 | 0.0 | 0.74 | −1.66 | −5.8 |
I-TASSER | 80.3 | 11.6 | 6.3 | 1.8 | 0.42 | −12.61 | −4.09 |
Phyre2.2 | 94.9 | 4.9 | 0.3 | 0.0 | 0.73 | −3.00 | −5.91 |
Ligand | ChemLP Score | Key Binding Residues | Redocking RMSD (Å) |
---|---|---|---|
Isoplumericin | 47.75 | Phe85, His183, Tyr86, Tyr151, Ile310, Ser306, Tyr302, Phe282, Asn202 | 0.132 |
Plumericin | 49.08 | His148, Phe85, Thr206, Asn202, Tyr151, Phe282, Gln286 | 0.051 |
Sucrose | 57.96 | Asn202, Glu147, Thr206, Ser82, Tyr151, Glu180 | 0.627 |
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Almeida, M.M.H.; da Cruz, J.D.; Silva, M.A.M.; Costa-Latgé, S.G.; Gomes, B.; Genta, F.A.; Silva, J.R.A.; Amaral, A.C.F. Iridoids from Himatanthus sucuuba Modulate Feeding Behavior of Lutzomyia longipalpis: Integrated Experimental and Computational Approaches. Molecules 2025, 30, 3937. https://doi.org/10.3390/molecules30193937
Almeida MMH, da Cruz JD, Silva MAM, Costa-Latgé SG, Gomes B, Genta FA, Silva JRA, Amaral ACF. Iridoids from Himatanthus sucuuba Modulate Feeding Behavior of Lutzomyia longipalpis: Integrated Experimental and Computational Approaches. Molecules. 2025; 30(19):3937. https://doi.org/10.3390/molecules30193937
Chicago/Turabian StyleAlmeida, Maíra M. H., Jefferson D. da Cruz, Maria Athana M. Silva, Samara G. Costa-Latgé, Bruno Gomes, Fernando A. Genta, Jefferson R. A. Silva, and Ana Claudia F. Amaral. 2025. "Iridoids from Himatanthus sucuuba Modulate Feeding Behavior of Lutzomyia longipalpis: Integrated Experimental and Computational Approaches" Molecules 30, no. 19: 3937. https://doi.org/10.3390/molecules30193937
APA StyleAlmeida, M. M. H., da Cruz, J. D., Silva, M. A. M., Costa-Latgé, S. G., Gomes, B., Genta, F. A., Silva, J. R. A., & Amaral, A. C. F. (2025). Iridoids from Himatanthus sucuuba Modulate Feeding Behavior of Lutzomyia longipalpis: Integrated Experimental and Computational Approaches. Molecules, 30(19), 3937. https://doi.org/10.3390/molecules30193937