In Vitro and In Silico Acetylcholinesterase Inhibitory Activity of Thalictricavine and Canadine and Their Predicted Penetration across the Blood-Brain Barrier
Abstract
:1. Introduction
2. Results and Discussion
2.1. AChE and BChE Inhibition Studies
2.2. AChE Kinetic Studies
2.3. Docking Studies
2.4. BBB Permeability
3. Materials and Methods
3.1. Instruments
3.2. Materials and Chemicals
3.3. AChE and BChE Inhibition
3.4. Kinetic Study of AChE Inhibition
3.5. Molecular Docking Studies
3.6. Prediction of CNS Permeability
4. Conclusions
Supplementary Materials
Author Contributions
Funding
Conflicts of Interest
References
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Sample Availability: Samples of the compounds 1 and 2 are available from the authors. |
Compounds | IC50 ± SEM (µM) 1 | PAMPA-BBB Permeability (Pe; 10−6 cm·s−1) 3 | LogBB 4 | ||
---|---|---|---|---|---|
hAChE | hBChE | SI 2 | |||
1 | 0.38 ± 0.05 | >100 | >263 | 2.5 ± 0.1 (CNS±) | −0.100 |
2 | 0.70 ± 0.07 | >100 | >143 | 5.0 ± 0.3 (CNS+) | 0.018 |
Gal 5 | 0.26 ± 0.01 | 18.0 ± 1.90 | 69 | n.d. 6 | n.d. 6 |
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Chlebek, J.; Korábečný, J.; Doležal, R.; Štěpánková, Š.; Pérez, D.I.; Hošťálková, A.; Opletal, L.; Cahlíková, L.; Macáková, K.; Kučera, T.; et al. In Vitro and In Silico Acetylcholinesterase Inhibitory Activity of Thalictricavine and Canadine and Their Predicted Penetration across the Blood-Brain Barrier. Molecules 2019, 24, 1340. https://doi.org/10.3390/molecules24071340
Chlebek J, Korábečný J, Doležal R, Štěpánková Š, Pérez DI, Hošťálková A, Opletal L, Cahlíková L, Macáková K, Kučera T, et al. In Vitro and In Silico Acetylcholinesterase Inhibitory Activity of Thalictricavine and Canadine and Their Predicted Penetration across the Blood-Brain Barrier. Molecules. 2019; 24(7):1340. https://doi.org/10.3390/molecules24071340
Chicago/Turabian StyleChlebek, Jakub, Jan Korábečný, Rafael Doležal, Šárka Štěpánková, Daniel I. Pérez, Anna Hošťálková, Lubomír Opletal, Lucie Cahlíková, Kateřina Macáková, Tomáš Kučera, and et al. 2019. "In Vitro and In Silico Acetylcholinesterase Inhibitory Activity of Thalictricavine and Canadine and Their Predicted Penetration across the Blood-Brain Barrier" Molecules 24, no. 7: 1340. https://doi.org/10.3390/molecules24071340