Single Crystal X-Ray Structure for the Disordered Two Independent Molecules of Novel Isoflavone: Synthesis, Hirshfeld Surface Analysis, Inhibition and Docking Studies on IKKβ of 3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-6,7-dimethoxy-4H-chromen-4-one
Abstract
:1. Introduction
2. Materials and Methods
2.1. General
2.2. Crystal Structure Determination
2.3. Hirshfeld Surfaces
2.4. In Silico Docking with IκB Kinaseβ (IKKβ)
2.5. Cells and Cell Culture
2.6. Western Blot Analysis
2.7. Clonogenic Assay
3. Results and Discussion
3.1. Synthesis
3.1.1. Synthesis of (E)-3-(dimethylamino)-1-(2-hydroxy-4,5-dimethoxyphenyl)prop-2-en-1-one (2)
3.1.2. Synthesis of 3-iodo-6,7-dimethoxy-4H-chromen-4-one (3)
3.1.3. Synthesis of 3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-6,7-dimethoxy-4H-chromen-4-one (5)
3.2. Crystal Structure of Isoflavone Compound 5
3.3. Hirshfeld Surface analysis of Compound 5
3.4. In Silico Docking with IKKβ
3.5. Effect of Compound 5 on the Inhibition of IKK Pathway
3.6. Effect of Compound 5 on the Inhibition of Clonogenicity of HCT116 Cells
4. Conclusions
Supplementary Materials
Author Contributions
Funding
Conflicts of Interest
References
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CCDC deposit number | 2027508 |
Empirical formula | C19 H16 O6 |
Formula weight | 340.32 |
Temperature | 223(2) K |
Wavelength | 0.71073 Å |
Crystal system | Monoclinic |
Space group | P21/c |
Unit cell dimensions | a = 12.0654(5) Å b = 11.0666(5) Å c = 123.9550(11) Å β = 101.3757(16)°. |
Volume | 3135.7(2) Å3 |
Z | 8 |
Density (calculated) | 1.442 Mg/m3 |
Absorption coefficient | 0.108 mm−1 |
F(000) | 1424 |
Crystal size | 0.393 × 0.305 × 0.134 mm3 |
Theta range for data collection | 1.722 to 28.347° |
Index ranges | −16 ≤ h ≤ 16, −14 ≤ k ≤ 14, −31 ≤ l ≤ 31 |
Reflections collected | 102751 |
Independent reflections | 7798 [R(int) = 0.0604] |
Completeness to theta = 25.242° | 99.7 % |
Max. and min. transmission | 0.7457 and 0.6970 |
Refinement method | Full-matrix least-squares on F2 |
Data/restraints/parameters | 7798/12/492 |
Goodness-of-fit on F2 | 1.063 |
Final R indices [I>2sigma(I)] | R1 = 0.0430, wR2 = 0.1004 |
R indices (all data) | R1 = 0.0666, wR2 = 0.1179 |
Largest diff. peak and hole | 0.226 and −0.206 e.Å−3 |
I | II | ||
---|---|---|---|
O(5)–C(18A) | 1.412(4) | O(11)–C(37A) | 1.447(3) |
O(5)–C(18B) | 1.513(7) | O(11)–C(37B) | 1.422(14) |
C(18A)–C(19A) | 1.506(8) | C(37A)–C(38A) | 1.507(6) |
C(18B)–C(19B) | 1.458(13) | C(37B)–C(38B) | 1.45(3) |
C(19A)–O(6) | 1.495(4) | C(38A)–O(12) | 1.452(3) |
C(19B)–O(6) | 1.402(6) | C(38B)–O(12) | 1.449(15) |
O(5)–C(18A)–C(19A) | 107.5(4) | O(11)–C(37A)–C(38A) | 109.2(3) |
C(18A)–C(19A)–O(6) | 109.5(4) | O(12)–C(38A)–C(37A) | 108.8(3) |
O(5)–C(18B)–C(19B) | 113.2(7) | C(38B)–C(37B)–O(11) | 110.9(15) |
O(6)–C(19B)–C(18B) | 106.5(8) | C(37B)–C(38B)–O(12) | 105.2(16) |
C(15)–O(6)–C(19A) | 111.59(18) | C(34)–O(12)–C(38A) | 113.50(15) |
C(15)–O(6)–C(19B) | 113.9(3) | C(34)–O(12)–C(38B) | 108.9(5) |
C(3)–C(4)–O(3)–C(10) | 10.6(3) | C(22)–C(23)–O(9)–C(29) | 2.6(2) |
C(6)–C(5)–O(4)–C(11) | −5.5(2) | C(25)–C(24)–O(10)–C(30) | −1.5(3) |
D–H…A | d(D–H) | d(H…A) | d(D…A) | <(DHA) |
---|---|---|---|---|
C(29)–H(29B)…O(1)#1 | 0.97 | 2.43 | 3.396(2) | 172.2 |
C(38A)–H(38B)…O(9)#2 | 0.98 | 2.46 | 3.396(3) | 157.8 |
C(10)–H(10B)…O(7)#3 | 0.97 | 2.48 | 3.424(2) | 165.6 |
C(37A)–H(37B)…O(11)#4 | 0.98 | 2.59 | 3.071(4) | 110.7 |
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Shin, S.Y.; Lee, Y.H.; Lim, Y.; Lee, H.J.; Lee, J.H.; Yoo, M.; Ahn, S.; Koh, D. Single Crystal X-Ray Structure for the Disordered Two Independent Molecules of Novel Isoflavone: Synthesis, Hirshfeld Surface Analysis, Inhibition and Docking Studies on IKKβ of 3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-6,7-dimethoxy-4H-chromen-4-one. Crystals 2020, 10, 911. https://doi.org/10.3390/cryst10100911
Shin SY, Lee YH, Lim Y, Lee HJ, Lee JH, Yoo M, Ahn S, Koh D. Single Crystal X-Ray Structure for the Disordered Two Independent Molecules of Novel Isoflavone: Synthesis, Hirshfeld Surface Analysis, Inhibition and Docking Studies on IKKβ of 3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-6,7-dimethoxy-4H-chromen-4-one. Crystals. 2020; 10(10):911. https://doi.org/10.3390/cryst10100911
Chicago/Turabian StyleShin, Soon Young, Young Han Lee, Yoongho Lim, Ha Jin Lee, Ji Hye Lee, Miri Yoo, Seunghyun Ahn, and Dongsoo Koh. 2020. "Single Crystal X-Ray Structure for the Disordered Two Independent Molecules of Novel Isoflavone: Synthesis, Hirshfeld Surface Analysis, Inhibition and Docking Studies on IKKβ of 3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-6,7-dimethoxy-4H-chromen-4-one" Crystals 10, no. 10: 911. https://doi.org/10.3390/cryst10100911