Identification of Antagonistic Action of Pyrrolizidine Alkaloids in Muscarinic Acetylcholine Receptor M1 by Computational Target Prediction Analysis
Abstract
:1. Introduction
2. Results
2.1. Target Prediction Analysis
2.2. Molecular Docking
2.3. Determination of Agonistic or Antagonistic Functions by a Calcium Efflux Assay
3. Discussion
4. Materials and Methods
4.1. Collection of Chemical Structures and Classification of PAs
4.2. Target Prediction with ChemMapper
4.3. Target Prediction Using SwissTargetPrediction
4.4. Analysis of Target Prediction
4.5. Molecular Docking
4.6. Determination of Agonistic/Antagonistic Activity by Calcium Efflux Assay
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Correction Statement
References
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Compound | Mean Binding Energy–VinaLC (kcal/mol) | pKi/nM | Amino Acids Involved in Interactions | Amino Acids Involved in H-Bonds |
---|---|---|---|---|
Pirenzepine | −7.42 (±0.32) | 2.74 × 103 (±0.09 × 103) | Trp101, Leu102, Tyr106, Cys178, Leu183, Trp400, Glu401, Tyr404 | |
Heliotrine | −5.31 (±0.34) | 36.27 × 103 (±7.08 × 103) | Tyr82, Tyr85, Cys98, Trp101, Tyr106, Cys178, Tyr179, Ile180, Leu183, Tyr381, Tyr404 | Tyr106, Cys178, Ile180 |
Rinderine | −5.62 (±0.12) | 39.69 × 103 (±7.08 × 103) | Leu102, Tyr106, Cys178, Tyr179, Ile180, Leu183, Thr189, Tyr381, Tyr404 | Ile180 (2), Tyr381 |
Lycopsamine | −5.71 (±0.13) | 4.44 × 106) (±0.68 × 106) | Tyr82, Tyr85, Leu86, Gly89, Glu397, Glu401, Tyr404 | Tyr82, Glu397, Glu401 |
Echimidine | −6.04 (±0.29) | 21.61 × 103 (±8.21 × 103) | Tyr82, Tyr85, Tyr106, Cys178, Tyr179, Ile180, Leu183, Thr189, Trp400, Glu401, Tyr404 | Thr189, Glu401 |
Lasiocarpine | −6.19 (±0.23) | 8.91 × 103 (±1.53 × 103) | Tyr82, Trp101, Leu102, Tyr106, Tyr179, Ile180, Leu183, Tyr381, Trp400, Glu401, Tyr404 | Ile180, Glu401 |
Echiumine | −6.06 (±0.19) | 16.99 × 103 (±2.51 × 103) | Tyr82, Tyr85, Tyr106, Cys178, Tyr179, Ile180, Leu183, Thr189, Trp400, Glu401, Tyr404 | Tyr106 |
Riddelliine | −7.17 (±0.42) | 4.67 × 103 (±0.04 × 103) | Tyr106, Cys178, Tyr179, Ile180, Leu183, Ser184, Thr189, Tyr404 | Ile180, Leu183 |
Senecionine | −7.36 (±0.42) | 8.44 × 103 (±0.0) | Trp101, Leu102, Tyr106, Cys178, Tyr179, Ile180, Leu183, Thr189, Tyr404 | Tyr404 |
Monocrotaline | −6.96 (±0.3) | 1.55 × 106 (±0.0) | Tyr85, Leu102, Tyr106, Cys178, Tyr179, Ile180, Leu183 | Tyr106 |
Casuarine | −5.06 (±0.18) | 9.84 × 106 (±0.66 × 106) | Tyr85, Leu86, Gly89, Gln177, Glu397, Glu401 | Leu86, Gln177, Glu397(2), Glu401 |
Tussilagine | −5.16 (±0.7) | 3.67 × 106 (±0.04 × 106) | Tyr106, Tyr179, Ile180, Leu183, Thr189 | Ile180 |
Crotanecine | −4.57 (±0.15) | 13.20 × 106 (±0.26 × 106) | Tyr85, Leu86, Gly89, Glu397, Glu401 | Glu397(2), Glu401 |
Otonecine | −4.74 (±0.16) | 10.20 × 106 (±0.06 × 106) | Tyr82, Tyr85, Gln177, Cys178, Glu501, Tyr404 | Tyr85, Gln177, Glu501 |
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Abdalfattah, S.; Knorz, C.; Ayoobi, A.; Omer, E.A.; Rosellini, M.; Riedl, M.; Meesters, C.; Efferth, T. Identification of Antagonistic Action of Pyrrolizidine Alkaloids in Muscarinic Acetylcholine Receptor M1 by Computational Target Prediction Analysis. Pharmaceuticals 2024, 17, 80. https://doi.org/10.3390/ph17010080
Abdalfattah S, Knorz C, Ayoobi A, Omer EA, Rosellini M, Riedl M, Meesters C, Efferth T. Identification of Antagonistic Action of Pyrrolizidine Alkaloids in Muscarinic Acetylcholine Receptor M1 by Computational Target Prediction Analysis. Pharmaceuticals. 2024; 17(1):80. https://doi.org/10.3390/ph17010080
Chicago/Turabian StyleAbdalfattah, Sara, Caroline Knorz, Akhtar Ayoobi, Ejlal A. Omer, Matteo Rosellini, Max Riedl, Christian Meesters, and Thomas Efferth. 2024. "Identification of Antagonistic Action of Pyrrolizidine Alkaloids in Muscarinic Acetylcholine Receptor M1 by Computational Target Prediction Analysis" Pharmaceuticals 17, no. 1: 80. https://doi.org/10.3390/ph17010080
APA StyleAbdalfattah, S., Knorz, C., Ayoobi, A., Omer, E. A., Rosellini, M., Riedl, M., Meesters, C., & Efferth, T. (2024). Identification of Antagonistic Action of Pyrrolizidine Alkaloids in Muscarinic Acetylcholine Receptor M1 by Computational Target Prediction Analysis. Pharmaceuticals, 17(1), 80. https://doi.org/10.3390/ph17010080