The Structural Basis of DL0410, a Novel Multi-Target Candidate Drug for the Treatment of Alzheimer’s Disease
Abstract
:1. Introduction
2. Materials and Methods
2.1. Materials
2.2. Crystal Preparation
2.3. Single Crystal Detection
2.4. Thermal Analyses
2.5. Molecular Docking
3. Results
3.1. The Crystal Structure of DL0410
3.2. Thermal Analyses
3.2.1. DSC Analysis
3.2.2. TGA Result
3.3. Molecular Docking of DL0410 with AChE, BuChE, and H3R
3.3.1. Molecular Docking of DL0410 with AChE
3.3.2. Molecular Docking of DL0410 with BuChE
3.3.3. Molecular Docking of DL0410 with H3R
4. Discussion and Conclusions
Author Contributions
Funding
Data Availability Statement
Conflicts of Interest
References
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Length [Å] | |
O1–C3 | 1.2184 (12) |
O2–H2C | 0.851 (16) |
O2–H2D | 0.829 (16) |
O3–H3A | 0.869 (15) |
O3–H3B | 0.873 (15) |
O4–H4A | 0.833 (15) |
O4–H4B | 0.869 (15) |
O5–H5A | 0.806 (17) |
O5–H5B | 0.856 (17) |
N1–C1 | 1.4943 (12) |
N1–C10 | 1.5012 (12) |
N1–C14 | 1.5055 (12) |
N1–H1 | 0.935 (14) |
C1–C2 | 1.5199 (13) |
C2–C3 | 1.5166 (13) |
C3–C4 | 1.4878 (13) |
C4–C5 | 1.3950 (12) |
C4–C9 | 1.3962 (12) |
C5–C6 | 1.3928 (12) |
C5–H5 | 0.9500 |
C6–C7 | 1.4024 (12) |
C6–H6 | 0.9500 |
C7–C8 | 1.4046 (12) |
C7–C7 #1 | 1.4907 (17) |
C8–C9 | 1.3853 (12) |
C8–H8 | 0.9500 |
C9–H9 | 0.9500 |
C10–C11 | 1.5217 (14) |
C11–C12 | 1.5190 (16) |
C12–C13 | 1.5251 (16) |
C13–C14 | 1.5145 (14) |
Atom–Atom–Atom | Angle [°] |
H2C–O2–H2D | 110 (2) |
H3A–O3–H3B | 105.6 (18) |
H4A–O4–H4B | 99.2 (18) |
H5A–O5–H5B | 108 (2) |
C1–N1–C10 | 113.63 (7) |
C1–N1–C14 | 108.41 (7) |
C10–N1–C14 | 111.26 (7) |
C1–N1–H1 | 109.1 (8) |
C10–N1–H1 | 106.4 (8) |
C14–N1–H1 | 107.8 (8) |
N1–C1–C2 | 114.96 (7) |
H1A–C1–H1B | 107.5 |
C3–C2–C1 | 108.96 (7) |
H2A–C2–H2B | 108.3 |
O1–C3–C4 | 120.20 (8) |
O1–C3–C2 | 120.17 (8) |
C4–C3–C2 | 119.61 (8) |
C5–C4–C9 | 118.89 (8) |
C5–C4–C3 | 122.89 (8) |
C9–C4–C3 | 118.20 (8) |
C6–C5–C4 | 120.27 (8) |
C6–C5–H5 | 119.9 |
C4–C5–H5 | 119.9 |
C5–C6–C7 | 121.35 (8) |
C5–C6–H6 | 119.3 |
C7–C6–H6 | 119.3 |
C6–C7–C8 | 117.50 (8) |
C6–C7–C7 #1 | 121.54 (9) |
C8–C7–C7 #1 | 120.96 (9) |
C9–C8–C7 | 121.25 (8) |
C9–C8–H8 | 119.4 |
C7–C8–H8 | 119.4 |
C8–C9–C4 | 120.64 (8) |
C8–C9–H9 | 119.7 |
C4–C9–H9 | 119.7 |
N1–C10–C11 | 111.03 (8) |
H10A–C10–H10B | 108.0 |
C12–C11–C10 | 111.99 (9) |
H11A–C11–H11B | 107.9 |
C11–C12–C13 | 109.94 (9) |
H12A–C12–H12B | 108.2 |
C14–C13–C12 | 110.60 (9) |
H13A–C13–H13B | 108.1 |
N1–C14–C13 | 111.77 (8) |
H14A–C14–H14B | 107.9 |
Atom–Atom–Atom–Atom | Torsion Angle [°] |
---|---|
C10–N1–C1–C2 | 56.79 (11) |
C14–N1–C1–C2 | −178.96 (8) |
N1–C1–C2–C3 | 173.39 (8) |
C1–C2–C3–O1 | 2.52 (14) |
C1–C2–C3–C4 | −178.57 (8) |
O1–C3–C4–C5 | 170.80 (10) |
C2–C3–C4–C5 | −8.12 (14) |
O1–C3–C4–C9 | −7.68 (15) |
C2–C3–C4–C9 | 173.40 (9) |
C9–C4–C5–C6 | 2.69 (15) |
C3–C4–C5–C6 | −175.78 (9) |
C4–C5–C6–C7 | −0.77 (16) |
C5–C6–C7–C8 | −2.02 (14) |
C5–C6–C7–C7 #1 | 178.07 (11) |
C6–C7–C8–C9 | 2.94 (14) |
C7 #1–C7–C8–C9 | −177.15 (10) |
C7–C8–C9–C4 | −1.07 (15) |
C5–C4–C9–C8 | −1.79 (14) |
C3–C4–C9–C8 | 176.75 (9) |
C1–N1–C10–C11 | 177.47 (8) |
C14–N1–C10–C11 | 54.78 (11) |
N1–C10–C11–C12 | −55.33 (12) |
C10–C11–C12–C13 | 55.63 (13) |
C11–C12–C13–C14 | −55.86 (12) |
C1–N1–C14–C13 | 178.11 (8) |
C10–N1–C14–C13 | −56.24 (11) |
C12–C13–C14–N1 | 56.78 (12) |
D–H⋯A [Å] | d(D–H) [Å] | d(H⋯A) [Å] | d(D⋯A) [Å] | <(DHA) [°] |
---|---|---|---|---|
O2–H2C⋯O4 #1 | 0.851 (16) | 1.975 (17) | 2.824 (8) | 175 (3) |
O2–H2D⋯Cl5 #2 | 0.829 (16) | 2.282 (18) | 3.079 (9) | 161 (3) |
O3–H3A⋯Cl5 | 0.869 (15) | 2.120 (15) | 2.981 (4) | 171 (2) |
O3–H3B⋯O2 #3 | 0.873 (15) | 2.023 (17) | 2.874 (9) | 165 (2) |
O4–H4A⋯Cl5 | 0.833 (15) | 2.281 (15) | 3.079 (2) | 161 (2) |
O4–H4B⋯O2 | 0.869 (15) | 2.095 (18) | 2.956 (9) | 171 (2) |
O5–H5A⋯Cl4 | 0.806 (17) | 2.05 (2) | 2.820 (11) | 161 (3) |
O5–H5B⋯Cl3 | 0.856 (17) | 2.166 (19) | 2.974 (6) | 157 (3) |
N1–H1⋯O3 | 0.935 (14) | 1.802 (14) | 2.736 (4) | 175.4 (12) |
N1–H1⋯Cl3 | 0.935 (14) | 2.063 (14) | 2.995 (4) | 174.1 (12) |
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Liu, A.; Zhao, J.; Huls, N.J.; Zeller, M.; Wang, L.; Li, T. The Structural Basis of DL0410, a Novel Multi-Target Candidate Drug for the Treatment of Alzheimer’s Disease. Crystals 2024, 14, 59. https://doi.org/10.3390/cryst14010059
Liu A, Zhao J, Huls NJ, Zeller M, Wang L, Li T. The Structural Basis of DL0410, a Novel Multi-Target Candidate Drug for the Treatment of Alzheimer’s Disease. Crystals. 2024; 14(1):59. https://doi.org/10.3390/cryst14010059
Chicago/Turabian StyleLiu, Ailin, Jun Zhao, Nicholas J. Huls, Matthias Zeller, Lin Wang, and Tonglei Li. 2024. "The Structural Basis of DL0410, a Novel Multi-Target Candidate Drug for the Treatment of Alzheimer’s Disease" Crystals 14, no. 1: 59. https://doi.org/10.3390/cryst14010059
APA StyleLiu, A., Zhao, J., Huls, N. J., Zeller, M., Wang, L., & Li, T. (2024). The Structural Basis of DL0410, a Novel Multi-Target Candidate Drug for the Treatment of Alzheimer’s Disease. Crystals, 14(1), 59. https://doi.org/10.3390/cryst14010059