Structure-Activity Relationships of Thiazolyl Resorcinols, Potent and Selective Inhibitors of Human Tyrosinase
Abstract
:1. Introduction
2. Results and Discussion
2.1. Structural Motifs Essential for Inhibition
2.2. Steric Factors
2.3. Homology Modeling
2.4. Molecular Docking
2.5. Role of the Thiazole Ring
3. Materials and Methods
3.1. Human Tyrosinase
3.2. Sources of Inhibitors
3.3. Tyrosinase Assay and Dose-Response Profiles
3.4. Molecular Modeling and Simulation
4. Conclusions
Supplementary Materials
Acknowledgments
Author Contributions
Conflicts of Interest
Abbreviations
bTyr | bacterial tyrosinase from B. megaterium |
hTyr | human tyrosinase |
mTyr | mushroom tyrosinase from A. bisporus |
sTyr | bacterial tyrosinase from S. castaneoglobisporus |
hTrp-1 | human tyrosinase-related protein 1 |
TM-score | template modelling score |
MVD | Molegro Virtual Docker |
nrSc | negative rerank score as calculated by MVD |
RSQ | residue-specific quality of an I-Tasser model |
RMSD | root mean square deviation |
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(a) | (b) | ||||
---|---|---|---|---|---|
Code | Structure | EC50 (µM) | Code | Structure | EC50 (µM) |
W311 | | 3.2 ± 0.1 | W547 | | 3.2 ± 0.6 |
W452 | | 19 ± 1 | W633 | | 750 ± 60 |
W539 | | >3000 | W548 | | 4.6 ± 0.2 |
W568 | | >3000 | W632 | | >3000 |
W480 | | >3000 | W607 | | 56 ± 3 |
W624 | | >3000 | W701 | | >3000 |
W056 | | 520 ± 50 |
Code | Core Structure | EC50 (µM) | nrSc | ||||
---|---|---|---|---|---|---|---|
W495 | | 51 ± 2 | 86 | ||||
(a) | |||||||
Code | Amines | EC50 (µM) | nrSc | Code | Amides | EC50 (µM) | nrSc |
W366 | | 33 ± 1 | - | W547 | | 3.2 ± 0.6 | 102 |
W538 | | 5.6 ± 1.4 | - | W577 | | 3.5 ± 0.5 | - |
W533 | | 6.2 ± 0.2 | - | W630 | | 1.1 ± 0.1 | 114 |
W534 | | 25 ± 1 | - | W687 | | 1.4 ± 0.1 | - |
W688 | | 60 ± 2 | - | W695 | | 15 ± 1 | - |
W694 | | 16 ± 1 | 93 | W548 | | 4.6 ± 0.2 | - |
W367 | | 10 ± 1 | - | W498 | | 2.5 ± 0.1 | - |
W693 | | 5.7 ± 0.2 | - | W619 | | 1.6 ± 0.4 | - |
(b) | |||||||
Code | R | EC50 (µM) | nrSc | Code | R | EC50 (µM) | nrSc |
W688 | | 60 ± 2 | - | W692 | | 6.9 ± 0.2 | - |
W669 | | 81 ± 5 | W680 | | 3.2 ± 0.2 | - | |
W619 | | 1.6 ± 0.4 | - | W696 | | 6.5 ± 0.2 | - |
W542 | | 9.8 ± 0.3 | 105 | W693 | | 5.7 ± 0.2 | - |
W367 | | 11 ± 1 | - | W496 | | 140 ± 6 | 86 |
W537 | | 160 ± 2 | - | ||||
W529 | | 2.6 ± 0.1 | - | W570 | | 3.5 ± 0.1 | 115 |
(a) | (b) | |||||
---|---|---|---|---|---|---|
Code | Structure | EC50 (µM) | nrSc | Code | Structure | EC50 (µM) |
W089 | | >3000 | 48 | W548 | | 4.6 ± 0.2 |
W039 | | 21 ± 4 | 92 | W605 | | 1400 ± 160 |
W785 | | 560 ± 90 | 66 | W625 | | >3000 |
W072 | | 93 ± 21 | 88 | W681 | | >3000 |
W038 | | 130 ± 10 | 84 | W694 | | 16 ± 1 |
W639 | | 220 ± 10 | - | W646 | | 40 ± 2 |
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Mann, T.; Scherner, C.; Röhm, K.-H.; Kolbe, L. Structure-Activity Relationships of Thiazolyl Resorcinols, Potent and Selective Inhibitors of Human Tyrosinase. Int. J. Mol. Sci. 2018, 19, 690. https://doi.org/10.3390/ijms19030690
Mann T, Scherner C, Röhm K-H, Kolbe L. Structure-Activity Relationships of Thiazolyl Resorcinols, Potent and Selective Inhibitors of Human Tyrosinase. International Journal of Molecular Sciences. 2018; 19(3):690. https://doi.org/10.3390/ijms19030690
Chicago/Turabian StyleMann, Tobias, Cathrin Scherner, Klaus-Heinrich Röhm, and Ludger Kolbe. 2018. "Structure-Activity Relationships of Thiazolyl Resorcinols, Potent and Selective Inhibitors of Human Tyrosinase" International Journal of Molecular Sciences 19, no. 3: 690. https://doi.org/10.3390/ijms19030690