Synthesis, Conformational Analysis and ctDNA Binding Studies of Flavonoid Analogues Possessing the 3,5-di-tert-butyl-4-hydroxyphenyl Moiety
Abstract
:1. Introduction
2. Materials and Methods
2.1. Synthesis and Characterization
General Procedure for the Synthesis of Flavanones 3–5
- 6-bromo-2-(3,5-di-tert-butyl-4-hydroxyphenyl) chromane-4-one (3)
- 6-chloro-2-(3,5,-di-tert-butyl-4-hydroxyphenyl) chromane-4-one (4)
- 3-(4′-hydroxy-3′,5′-di-tert-butylbenzylidene)-4″-hydroxy-3″,5″-di-tert-butyl-flavanone (5)
- 2′,4-Dihydroxy-3,5-di-(tert-butyl)-chalcone (6)
2.2. In Vitro Assays
2.2.1. DPPH Radical Scavenging Ability
2.2.2. Inhibition of AAPH Induced Linoleic Acid Oxidation
2.2.3. DNA Binding Studies Using UV-Vis Spectroscopy
2.3. Molecular Docking
2.4. Conformational Analysis
2.5. Calculation of Physicochemical Properties
3. Results
3.1. Chemistry
3.2. Antioxidant Activity
3.3. Binding Studies with ct-DNA Using UV Spectroscopy
3.4. Molecular Docking
3.5. Conformational Analysis of the Synthesized Compounds
3.6. Calculation of Physicochemical Properties
4. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
Appendix A
References
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Compound | Structure | % Inhibition of DPPH Free Radical (100μM) | % Inhibition of Lipid Peroxidation of Linoleic Acid Induced by AAPH Radical (100 μM) | |
---|---|---|---|---|
30 min | 60 min | |||
3 | 29.3 | 28.2 | 21.1 | |
4 | 32.0 | 39.6 | 59.3 | |
5 | 70.8 | 60.2 | 77.4 | |
6 | 61.1 | 39.9 | 54.6 | |
TROLOX | 82.4 | 83.4 | 81.4 |
Compound | Structure | Κb (M−1) |
---|---|---|
3 | 0.1 103 | |
4 | 2.4 103 | |
5 | 3.4 103 | |
6 | 5.0 103 | |
Rhodamine B | 2.2 104 | |
Methyl Green | 2.0 103 |
Compound | Binding Energy (kcal/mol) | Inhibition Constant Ki | vdW + Bond + Desolve Energy (kcal/mol) | Electrostatic Energy (kcal/mol) |
---|---|---|---|---|
3 | −9.01 | 250.10 nM | −10.10 | −0.10 |
4 | −8.97 | 316.49 nM | −9.97 | −0.09 |
5 | −6.35 | 22.11 μM | −8.64 | −0.10 |
6 | −9.06 | 229.64 nM | −11.52 | +0.07 |
Physicochemical Property | Compounds | |||
---|---|---|---|---|
3 | 4 | 5 | 6 | |
Dipole | 4.97 | 5.26 | 5.87 | 4.81 |
SASA | 687.00 | 681.97 | 893.34 | 680.30 |
FOSA | 412.17 | 412.12 | 642.62 | 378.37 |
FISA | 57.75 | 57.76 | 49.28 | 90.75 |
PISA | 139.80 | 140.52 | 201.43 | 211.18 |
WPSA | 77.33 | 71.58 | 0 | 0 |
volume | 1256.42 | 1247.51 | 1852.64 | 1231.98 |
donorHB | 1 | 1 | 2 | 1 |
accptHB | 3.5 | 3.5 | 4.25 | 2.5 |
dip2/V | 0.019641 | 0.0222095 | 0.0186334 | 0.0187806 |
QPpolrz | 43.54 | 43.19 | 64.77 | 40.03 |
QPlogPC16 | 12.06 | 11.94 | 17.30 | 12.02 |
QPlogPoct | 17.94 | 17.83 | 26.99 | 15.87 |
QPlogPw | 6.99 | 6.98 | 8.92 | 5.57 |
QPlogPo/w | 5.77 | 5.69 | 8.90 | 5.60 |
QPlogS | −7.36 | −7.24 | −9.49 | −6.46 |
IP(eV) | 9.04 | 9.03 | 8.88 | 8.86 |
EA(eV) | 0.79 | 0.77 | 0.71 | 0.88 |
PSA | 47.40 | 47.40 | 57.11 | 58.20 |
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Tzani, A.; Kritsi, E.; Tsamantioti, L.; Kostopoulou, I.; Karadendrou, M.-A.; Zoumpoulakis, P.; Detsi, A. Synthesis, Conformational Analysis and ctDNA Binding Studies of Flavonoid Analogues Possessing the 3,5-di-tert-butyl-4-hydroxyphenyl Moiety. Antioxidants 2022, 11, 2273. https://doi.org/10.3390/antiox11112273
Tzani A, Kritsi E, Tsamantioti L, Kostopoulou I, Karadendrou M-A, Zoumpoulakis P, Detsi A. Synthesis, Conformational Analysis and ctDNA Binding Studies of Flavonoid Analogues Possessing the 3,5-di-tert-butyl-4-hydroxyphenyl Moiety. Antioxidants. 2022; 11(11):2273. https://doi.org/10.3390/antiox11112273
Chicago/Turabian StyleTzani, Andromachi, Eftichia Kritsi, Lamprini Tsamantioti, Ioanna Kostopoulou, Maria-Anna Karadendrou, Panagiotis Zoumpoulakis, and Anastasia Detsi. 2022. "Synthesis, Conformational Analysis and ctDNA Binding Studies of Flavonoid Analogues Possessing the 3,5-di-tert-butyl-4-hydroxyphenyl Moiety" Antioxidants 11, no. 11: 2273. https://doi.org/10.3390/antiox11112273