Oxidative Degradation of High-Molar-Mass Hyaluronan: Effects of Some Indole Derivatives to Hyaluronan Decay
<p>Isatin (<b>1</b>), cemtirestat (<b>2</b>), stobadine (<b>3</b>), SME1i-ProC2 (<b>4</b>), and SM1M3EC2 (<b>5</b>).</p> "> Figure 2
<p>Percentage of inhibition of HA degradation within 120 min. Stobadine⋅2HCl dihydrochloride, i.e., compound (<b>3</b>), and two of its derivatives ((<b>4</b>) and (<b>5</b>)) were examined as preventive antioxidants (left panel) and chain-breaking antioxidants (right panel).</p> "> Figure 3
<p>Time-dependent changes in dynamic viscosity of HA solutions exposed to oxidative degradation initiated by Cu(II) ions and ascorbate (black curve). Cemtirestat was added to the reaction mixture before HA degradation begins (left panel) or 1 h later (right panel) at micromolar concentrations: 25 (red), 10 (green) and 1 (blue).</p> "> Figure 4
<p>Time-dependent changes in dynamic viscosity of HA solutions exposed to oxidative degradation initiated by Cu(II) ions and ascorbate (black curve). Isatin was added to the HA reaction mixture before HA degradation begins (left panel) and 1 h later (right panel) at micromolar concentrations: 100 (cyan), 10 (green) and 1 (blue).</p> "> Scheme 1
<p>Reaction of initiation: (<b>a</b>) An intact HA macromolecule reacts with <sup>•</sup>OH radical; (<b>b</b>) formation of an intermediate, i.e., a <span class="html-italic">C</span>-centered HA macroradical (denoted later A<sup>•</sup>). Reactions of propagation and of transfer of free-radical centre: (<b>c</b>) formation of peroxy-type macroradical; (<b>d</b>) and (<b>e</b>) generation of HA hydroperoxide and a highly unstable alkoxy-type macroradical. The reaction yielding fragments: (<b>f</b>) alkoxy-type macroradical and HA macromolecule bearing a terminal C=O group. Both fragments are represented by reduced molar masses. (Hrabárová et al. (2012) [<a href="#B3-ijms-21-05609" class="html-bibr">3</a>]).</p> ">
Abstract
:1. Introduction
2. Results
3. Discussion
4. Materials and Methods
4.1. Materials
4.2. Preparation of Stock and Working Solutions
4.3. Study of Uninhibited/Inhibited Hyaluronan Degradation
- (a)
- The stock solution of CuCl2 in the volume of 50 µL was added to the HA solution (7.85 mL), which after stirring for 30 s was left to stand for 7 min 30 s at room temperature. Then, 50 µL of the appropriately diluted stock solution of compound (1) or (2) was added and the solution was stirred again for 30 s. Finally, 50 µL of stock l-ascorbic acid solution was added and the completed solution was stirred for 30 s. The solution mixture was then immediately transferred into the viscometer Teflon® cup reservoir.
- (b)
- In the second experimental setting a similar procedure as that described in (a) was applied, however, after the reaction mixture standing for 7 min 30 s at room temperature, 50 µL of stock l-ascorbic acid solution was added. After 1-h stirring of the reaction mixture, finally 50 µL of the appropriately diluted stock solution of the compound (1) or (2) was added and stirred again for 30 s. The reaction mixture was then immediately transferred into the viscometer Teflon® cup reservoir.
4.4. ABTS and DPPH Assays—Determination of IC50 Values
5. Conclusions
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
Abbreviations
ABTS | 2,2′-Azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt |
DPP• | 2,2-Diphenyl-1-picrylhydrazyl radical |
HA | Hyaluronan |
ROS | Reactive oxygen species |
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Redox Couple a | E°′/mV |
---|---|
HO•, H+/H2O | + 2310 |
RO•, H+/ROH (aliphatic alkoxyl radical) | + 1600 |
ROO•, H+/ROOH (aliphatic peroxyl radical) | + 1000 |
GS•/GS− (glutathione) | + 920 |
TO•, H+/TOH (tocopherol) | + 480 |
H2O2, H+/H2O, HO• | + 320 |
Asc•−, H+/AscH− (ascorbate) | + 282 |
O2/ O2•− | − 160 |
RSSR/ RSSR•− (e.g., oxidized glutathione) | − 1500 |
H2O/e−aq | − 2870 |
Compound | IC50 [µmol/L] |
---|---|
1. Isatin a | undeterminable |
2. Cemtirestat | 26 ± 1.8 |
3. Stobadine·2HCl b | 12.6 ± 0.24 |
4. SME1i-ProC2·HCl c | 27.6 ± 0.46 |
5. SM1M3EC2·HCl d | 10.8 ± 0.38 |
Compound | IC50 [µmol/L] |
---|---|
1. Isatin a | 203 |
2. Cemtirestat | 2.9 ± 0.3 |
3. Stobadine·2HCl b | 122 ± 5 |
4. SME1i-ProC2·HCl c | 10.6 ± 0.5 |
5. SM1M3EC2·HCl d | 21 ± 1.4 |
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Valachová, K.; Mach, M.; Šoltés, L. Oxidative Degradation of High-Molar-Mass Hyaluronan: Effects of Some Indole Derivatives to Hyaluronan Decay. Int. J. Mol. Sci. 2020, 21, 5609. https://doi.org/10.3390/ijms21165609
Valachová K, Mach M, Šoltés L. Oxidative Degradation of High-Molar-Mass Hyaluronan: Effects of Some Indole Derivatives to Hyaluronan Decay. International Journal of Molecular Sciences. 2020; 21(16):5609. https://doi.org/10.3390/ijms21165609
Chicago/Turabian StyleValachová, Katarína, Mojmír Mach, and Ladislav Šoltés. 2020. "Oxidative Degradation of High-Molar-Mass Hyaluronan: Effects of Some Indole Derivatives to Hyaluronan Decay" International Journal of Molecular Sciences 21, no. 16: 5609. https://doi.org/10.3390/ijms21165609