(S)-5-Methylmellein Isolated from an Endogenous Lichen Fungus Rosellinia corticium as a Potent Inhibitor of Human Monoamine Oxidase A
Abstract
:1. Introduction
2. Materials and Methods
2.1. Obtaining and Preparation of ELF Extracts to Assess MAO-A Inhibitory Activity
2.2. Enzyme Activity Assays
2.3. Culture and Extraction of ELF68
2.4. Isolation and Identification of Compounds
2.5. Kinetic Study of the Compounds
2.6. Analysis of Inhibitor Reversibility
2.7. Molecular Docking Simulation of the Compound with hMAO-A and hMAO-B
2.8. Analysis of Pharmacokinetic and Physicochemical Parameters In Silico
3. Results
3.1. Inhibitory Activity of ELF Extracts against hMAO-A
3.2. Compound Isolation of ELF68 Using Prep TLC
3.3. Identification of ELF68
3.4. Inhibitory Activities of 5MM against MAOs, ChEs, and BACE1
3.5. Kinetic Studies of 5MM
3.6. Analysis of Reversibility for hMAO-A by 5MM
3.7. Molecular Docking Simulation
3.8. In Silico Pharmacokinetics of 5MM
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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ELF No. | Residual Activity at 20 µg/mL (%) | |
---|---|---|
hMAO-A | hMAO-B | |
56 | 51.1 ± 2.2 | 34.7 ± 1.7 |
62 | 50.4 ± 1.1 | 43.7 ± 2.0 |
68 | 26.2 ± 5.8 | 61.8 ± 4.3 |
71 | 43.6 ± 2.5 | 72.7 ± 2.5 |
82 | 58.3 ± 3.2 | 52.2 ± 1.2 |
100 | 42.3 ± 1.0 | 43.9 ± 5.7 |
116 | 50.0 ± 4.6 | 56.4 ± 2.3 |
Residual Activity at 10 µM (%) | ||||||
---|---|---|---|---|---|---|
hMAO-A | hMAO-B | AChE | BChE | BACE1 | ||
5MM | 35.2 ± 0.9 | 44.5 ± 2.6 | 71.4 ± 2.1 | 92.5 ± 2.5 | 93.3 ± 2.7 | |
IC50 (µM) | SI | |||||
hMAO-A | hMAO-B | AChE | BChE | BACE1 | ||
5MM | 5.31 ± 0.24 | 9.15 ± 0.92 | 27.07 ± 0.04 | >40 | >40 | 1.72 |
Toloxatone | 1.08 ± 0.03 | |||||
Clorgyline | 0.007 ± 0.001 | |||||
Lazabemide | 0.063 ± 0.015 | |||||
Pargyline | 0.028 ± 0.004 | |||||
Donepezil | 0.009 ± 0.002 | 0.180 ± 0.004 | ||||
Quercetin | 20.46 ± 0.60 |
Compound | GI Absorption | BBB Permeant | P-gp Substrate | CYP1A2 Inhibitor | CYP2C19 Inhibitor | CYP2C9 Inhibitor | CYP2D6 Inhibitor | CYP3A4 Inhibitor | Log Kp (Skin Permeation) |
---|---|---|---|---|---|---|---|---|---|
5MM | High | Yes | No | Yes | No | No | No | No | −5.48 cm/s |
Compound | Mw(g/mol) | cLog P | HBD | HBA | TPSA (Å2) | RB | Lipinski Violations |
---|---|---|---|---|---|---|---|
5MM | 192.21 | 2.19 | 1 | 3 | 46.53 | No | 0 |
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Jeong, G.-S.; Lee, E.-Y.; Kang, M.-G.; Nam, S.-J.; Park, D.; Kim, H. (S)-5-Methylmellein Isolated from an Endogenous Lichen Fungus Rosellinia corticium as a Potent Inhibitor of Human Monoamine Oxidase A. Processes 2022, 10, 166. https://doi.org/10.3390/pr10010166
Jeong G-S, Lee E-Y, Kang M-G, Nam S-J, Park D, Kim H. (S)-5-Methylmellein Isolated from an Endogenous Lichen Fungus Rosellinia corticium as a Potent Inhibitor of Human Monoamine Oxidase A. Processes. 2022; 10(1):166. https://doi.org/10.3390/pr10010166
Chicago/Turabian StyleJeong, Geum-Seok, Eun-Young Lee, Myung-Gyun Kang, Sang-Jip Nam, Daeui Park, and Hoon Kim. 2022. "(S)-5-Methylmellein Isolated from an Endogenous Lichen Fungus Rosellinia corticium as a Potent Inhibitor of Human Monoamine Oxidase A" Processes 10, no. 1: 166. https://doi.org/10.3390/pr10010166
APA StyleJeong, G.-S., Lee, E.-Y., Kang, M.-G., Nam, S.-J., Park, D., & Kim, H. (2022). (S)-5-Methylmellein Isolated from an Endogenous Lichen Fungus Rosellinia corticium as a Potent Inhibitor of Human Monoamine Oxidase A. Processes, 10(1), 166. https://doi.org/10.3390/pr10010166