New Tacrine Analogs as Acetylcholinesterase Inhibitors — Theoretical Study with Chemometric Analysis
Abstract
:1. Introduction
2. Results and Discussion
2.1. Genotoxicity
2.2. Cardiotoxicity
2.3. P-Glycoprotein Specificity
2.4. Blood Brain Barier (BBB) Penetration
- -
- rate of brain penetration (LogPS); this parameter depends on essential physicochemical properties such as lipophilicity, ionization constants, hydrogen bonding parameters, and molecular size;
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- extent of brain penetration (LogBB); cumulative effect of drug binding to brain and plasma (LogBB is assumed to correspond to the passive transport across blood-brain barrier);
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- brain/plasma equilibration rate (Log(PS*fu,brain)); fu,brain – fraction unbound in plasma, calculated automatically [23].
2.5. Distribution
2.6. EC50 and LC50
2.7. Docking Studies and Pharmacophore Search
2.8. Chemometric Analysis
3. Experimental
3.1. Genotoxicity
- -
- the Ames test to provide the mutagenic potential of new compounds
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- a knowledge-based system in identifying and visualizing hazardous fragments of structures.
3.2. Cardiotoxicity
3.3. P-Glycoprotein Specificity
3.4. Blood Brain Barier (BBB) Penetration
3.5. Distribution
3.6. EC50 and LC50
3.7. Molecular Modeling
3.8. ATR-FT-IR and Multivariate Chemometric Analysis
4. Conclusions
Supplementary Materials
Acknowledgments
References
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Szymański, P.; Skibiński, R.; Inglot, T.; Bajda, M.; Jończyk, J.; Malawska, B.; Mikiciuk-Olasik, E. New Tacrine Analogs as Acetylcholinesterase Inhibitors — Theoretical Study with Chemometric Analysis. Molecules 2013, 18, 2878-2894. https://doi.org/10.3390/molecules18032878
Szymański P, Skibiński R, Inglot T, Bajda M, Jończyk J, Malawska B, Mikiciuk-Olasik E. New Tacrine Analogs as Acetylcholinesterase Inhibitors — Theoretical Study with Chemometric Analysis. Molecules. 2013; 18(3):2878-2894. https://doi.org/10.3390/molecules18032878
Chicago/Turabian StyleSzymański, Paweł, Robert Skibiński, Tadeusz Inglot, Marek Bajda, Jakub Jończyk, Barbara Malawska, and Elżbieta Mikiciuk-Olasik. 2013. "New Tacrine Analogs as Acetylcholinesterase Inhibitors — Theoretical Study with Chemometric Analysis" Molecules 18, no. 3: 2878-2894. https://doi.org/10.3390/molecules18032878