Anticandidal Activity of In Situ Methionine γ-Lyase-Based Thiosulfinate Generation System vs. Synthetic Thiosulfinates
Abstract
:1. Introduction
2. Results and Discussion
2.1. 1H NMR Kinetic Study of β-Elimination Reaction of S-alk(en)yl-L-Cysteine Sulfoxides Catalyzed by C115HMGL
2.2. Antifungal Activity of Synthetic Dialk(en)ylthiosulfinates and TGS against C. albicans
2.3. Combinatorial Effect of Synthetic Dialk(en)ylthiosulfinates and TGS with Known Therapeutic Drugs
3. Materials and Methods
3.1. Materials
3.2. Apparatus
3.3. Synthesis of Dialk(en)ylthiosulfinates
3.4. Preparation of the C115H MGL
3.5. Kinetic Measurement via 1H NMR
3.6. Determination of Enzymatically Generated Dialk(en)ylthiosulfinates
3.7. Cell Culture
3.8. Antifungal Activity Evaluation
3.9. Checkerboard Assay
3.10. Statistical Analysis
4. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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DMTS | |
low field | CH3: 3.04 (s) |
high field | CH3: 2.66 (s) |
DETS | |
low field | CH3: 1.40 (t, 7.4 Hz) |
high field | CH3: 1.33 (t) |
other signals | 3.27 (dq), 3.19 (dq), 3.18 (q) |
DPTS | |
low field | CH3: 1.02 (t, 7.4 Hz) |
high field | CH3: 0.97 (t) |
other signals | 3.12–3.24 (m), 1.68–1.85 (m) |
DATS | |
low field | =CH2 (cis): 5.49 (d 1, 10.1 Hz)=CH2 (trans): 5.46 (d 1, 16.9 Hz) |
high field | =CH2 (cis): 5.22 (d 1)=CH2 (trans): 5.32 (d 1) |
other signals | 5.80–6.04 (m), 3.74–4.01 2 (m) |
Pyruvate | 2.33 (s) |
DMTS | DETS | DPTS | DATS | |
---|---|---|---|---|
Initial turnover rate 1, s−1 | 0.23 ± 0.01 | 1.03 ± 0.09 | 0.97 ± 0.04 | 1.56 ± 0.04 |
Turnover rate at half-conversion, s−1 | 0.07 ± 0.002 | 0.39 ± 0.01 | 0.39 ± 0.01 | 0.75 ± 0.08 |
Half-conversion time, min | 231 | 29 | 29 | 14 |
Reaction slowdown rate 2 | 70% | 62% | 60% | 52% |
Antimycotic Drug | C. albicans, MIC ± CI (95%) | |
---|---|---|
μg/mL | μM | |
Synthetic thiosulfinates | ||
DMTS | 2.68 ± 0.57 | 24 ± 5.1 |
DETS | 0.72 ± 0.16 | 5.2 ± 1.15 |
DPTS | 0.69 ± 0.26 | 4.1 ± 1.54 |
DATS | 3.31 ± 1.10 | 20 ± 6.65 |
TGSs | ||
C115H MGL/methiin | 1.11 ± 0.22 | 10 ± 1.98 |
C115H MGL/ethiin | 0.41 ± 0.09 | 3 ± 0.66 |
C115H MGL/propiin | 0.36 ± 0.09 | 2.2 ± 0.55 |
C115H MGL/alliin | 0.39 ± 0.07 | 2.4 ± 0.43 |
Commercial drugs | ||
AmpB | 0.46 ± 0.25 | 0.5 ± 0.27 |
FLC | 1.06 ± 0.21 | 3.5 ± 0.69 |
5-FC | 0.16 ± 0.03 | 1.2 ± 0.22 |
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Revtovich, S.; Lyfenko, A.; Tkachev, Y.; Kulikova, V.; Koval, V.; Puchkov, V.; Anufrieva, N.; Solyev, P.; Morozova, E. Anticandidal Activity of In Situ Methionine γ-Lyase-Based Thiosulfinate Generation System vs. Synthetic Thiosulfinates. Pharmaceuticals 2023, 16, 1695. https://doi.org/10.3390/ph16121695
Revtovich S, Lyfenko A, Tkachev Y, Kulikova V, Koval V, Puchkov V, Anufrieva N, Solyev P, Morozova E. Anticandidal Activity of In Situ Methionine γ-Lyase-Based Thiosulfinate Generation System vs. Synthetic Thiosulfinates. Pharmaceuticals. 2023; 16(12):1695. https://doi.org/10.3390/ph16121695
Chicago/Turabian StyleRevtovich, Svetlana, Anna Lyfenko, Yaroslav Tkachev, Vitalia Kulikova, Vasiliy Koval, Vladimir Puchkov, Natalya Anufrieva, Pavel Solyev, and Elena Morozova. 2023. "Anticandidal Activity of In Situ Methionine γ-Lyase-Based Thiosulfinate Generation System vs. Synthetic Thiosulfinates" Pharmaceuticals 16, no. 12: 1695. https://doi.org/10.3390/ph16121695