Baicalein as a Potential Inhibitor against BACE1 and AChE: Mechanistic Comprehension through In Vitro and Computational Approaches
Abstract
:1. Introduction
2. Materials and Methods
2.1. Chemicals and Reagent
2.2. Enzymatic Assay for Biological Evaluation
2.3. Kinetic Studies of Baicalein on BACE1 and AChE
2.4. In Silico Molecular Docking Studies and Drug-Likeness Prediction
2.5. Statistical Analysis
3. Results and Discussion
3.1. In Vitro Inhibitory Activity of Baicalein against BACE1 and AChE
3.2. Enzyme Kinetic Analysis of BACE1 and AChE Inhibition
3.3. Selectivity of Baicalein against BACE1
3.4. In Silico Docking Simulation of Baicalein and Its Drug-Likeness Prediction
4. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
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Compounds | BACE1 | AChE | ||||
---|---|---|---|---|---|---|
IC50 1 | Ki Value 2 | Inhibition Type 3 | IC50 | Ki Value | Inhibition Type | |
Baicalein | 23.71 ± 1.91 | 27.6 | Non-competitive | 45.95 ± 3.44 | 35.9 | Competitive |
Resveratrol 4 | 15.04 ± 0.87 | |||||
Galantamine 5 | 1.30 ± 0.01 |
Baicalein (μM) | TACE | Trypsin | Chymotrypsin | Elastase |
---|---|---|---|---|
50 | 8.31 ± 0.89 | 3.40 ± 0.76 | 8.42 ± 0.76 | 10.29 ± 1.04 |
100 | 9.45 ± 0.71 | −6.95 ± 0.87 | 4.48 ± 0.76 | 9.00 ± 0.45 |
Enzymes | Lowest Energy (Kcal/moL) | No. of H-Bond 1 | Residues | Bond Distance (Å) | Van der Waals Interacting Residues |
---|---|---|---|---|---|
BACE1 | −8.60 | 6 | Ser35 | 3.15 | Val69, Tyr71, Trp76, Phe108, Ile118, Ala127, Arg128 |
Ser36 | 3.27 | ||||
Asn37 | 2.85 and 2.88 | ||||
Ile126 | 2.66 and 2.89 | ||||
AChE | −8.70 | 3 | Glu202 | 2.88 and 2.94 | Tyr72, Asp74, Trp86, Asn87, Gly120, Gly121, Tyr124, Ser125, Ser203, Tyr337, Gly448 |
His447 | 2.96 | ||||
P-gp | −8.40 | 3 | Ser975 | 3.08 and 3.33 | Met68, Phe71, Phe332, Phe724, Phe728, Leu971, Phe974, Val978 |
Ser725 | 2.85 |
Compounds | No. of Violations | MW (g/moL) | H-Bond Acceptor | H-Bond Donor | Log Po/w 1 | TPSA 2 (Å2) | No. of rotb 3 |
---|---|---|---|---|---|---|---|
Baicalein | 0 | 270.24 | 5 | 3 | 2.682 | 90.89 | 1 |
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Han, J.; Ji, Y.; Youn, K.; Lim, G.; Lee, J.; Kim, D.H.; Jun, M. Baicalein as a Potential Inhibitor against BACE1 and AChE: Mechanistic Comprehension through In Vitro and Computational Approaches. Nutrients 2019, 11, 2694. https://doi.org/10.3390/nu11112694
Han J, Ji Y, Youn K, Lim G, Lee J, Kim DH, Jun M. Baicalein as a Potential Inhibitor against BACE1 and AChE: Mechanistic Comprehension through In Vitro and Computational Approaches. Nutrients. 2019; 11(11):2694. https://doi.org/10.3390/nu11112694
Chicago/Turabian StyleHan, Jin, Yeongseon Ji, Kumju Youn, GyuTae Lim, Jinhyuk Lee, Dong Hyun Kim, and Mira Jun. 2019. "Baicalein as a Potential Inhibitor against BACE1 and AChE: Mechanistic Comprehension through In Vitro and Computational Approaches" Nutrients 11, no. 11: 2694. https://doi.org/10.3390/nu11112694