Discovery of New Microbial Collagenase Inhibitors
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Collagenase Activity Assay
2.2. Molecular Docking
2.3. Statistical Analysis
3. Results
3.1. Collagenase Activity Assay
3.2. Molecular Docking Simulation
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Compound | Inhibition (%) | ||||
---|---|---|---|---|---|
1 µM | 5 µM | 10 µM | 50 µM | 100 µM | |
Palmatine chloride | 15.5 ± 3.9 | 35.4 ± 1.8 | 84.9 ± 1.5 | 97.9 ± 1.6 | 98.7 ± 0.4 |
Piperine | 84.5 ± 0.4 | 82.4 ± 0.4 | 72.5 ± 2.7 | NT * | NT * |
2′-Hydroxychalcone | −12.1 ± 0.2 | 1.2 ± 0.9 | 6.5 ± 1.3 | 21.8 ± 1.2 | 97.3 ± 1.3 |
3-Hydroxyflavone | −13.4 ± 2.7 | −17.0 ± 5.1 | 17.4 ± 4.5 | 25.1 ± 6.8 | 31.0 ± 4.3 |
Myricetin | −15.4 ± 2.7 | −4.5 ± 1.1 | −1.0 ± 1.1 | 13.6 ± 0.6 | 23.2 ± 2.0 |
Myricitrin | −37.9 ± 2.3 | −17.4 ± 2.4 | −20.8 ± 1.0 | 16.7 ± 3.1 | 37.2 ± 3.8 |
Dihydrorobinetin | −16.5 ± 1.6 | −29.7 ± 0.5 | 105.1 ± 0.5 | NT * | NT * |
Primuletin | −9.3 ± 1.7 | −8.8 ± 2.1 | −0.7 ± 1.3 | 8.5 ± 2.1 | 25.4 ± 1.8 |
4′,5-Dihydroxyflavone | −48.0 ± 3.6 | 101.6 ± 0.6 | 107.5 ± 1.0 | 101.0 ± 1.9 | 104.8 ± 2.9 |
Biochanin A | −24.8 ± 5.3 | 23.0 ± 2.6 | 34.1 ± 2.2 | 99.1 ± 1.0 | 76.1 ± 0.7 |
Juglone | 13.8 ± 1.5 | 50.6 ± 0.5 | 69.2 ± 0.4 | 80.8 ± 0.7 | 94.8 ± 0.1 |
Rhein | 2.6 ± 0.6 | 22.9 ± 2.7 | 37.4 ± 3.2 | 77.3 ± 2.2 | 80.6 ± 1.0 |
Curcumin | −10.0 ± 3.9 | 101.8 ± 0.6 | 102.5 ± 0.8 | 101.5 ± 0.4 | 101.8 ± 0.7 |
Capsaicin | 94.8 ± 0.8 | 100.5 ± 0.8 | NT * | NT * | NT * |
Citrulline | −4.3 ± 3.5 | −14.1 ± 1.4 | 27.8 ± 3.0 | 24.3 ± 1.7 | 7.2 ± 0.5 |
6-Methoxy-1,2,3,4-tetrahydro-9H-pyrido [3,4-b]indole-1-carboxylic acid | −19.9 ± 2.7 | −1.3 ± 2.1 | −5.2 ± 0.7 | 2.8 ± 1.3 | 19.6 ± 3.9 |
Compound | IC50 (µM) | 95% CI of IC50 (µM) | r2 |
---|---|---|---|
Palmatine chloride | 5.139 | 0.1076 to 245.4 | 0.918 |
Piperine | <1 | NC * | NC * |
2′-Hydroxychalcone | 60.395 | NC * | NC * |
3-Hydroxyflavone | >100 | NC * | NC * |
Myricetin | >100 | NC * | NC * |
Myricitrin | >100 | NC * | NC * |
Dihydrorobinetin | <10 | NC * | NC * |
Primuletin | >100 | NC * | NC * |
4′,5-Dihydroxyflavone | <1 | NC * | NC * |
Biochanin A | 12.474 | 0.2371 to 167.3 | 0.939 |
Juglone | 3.473 | 0.5838 to 20.66 | 0.984 |
Rhein | 12.710 | 5.225 to 30.92 | 0.996 |
Curcumin | <5 | NC * | NC * |
Capsaicin | <1 | NC * | NC * |
Citrulline | >100 | NC * | NC * |
6-Methoxy-1,2,3,4-tetrahydro-9H-pyrido [3,4-b]indole-1-carboxylic acid | >100 | NC * | NC * |
1,10-Phenanthroline | 114.810 | NC * | NC * |
Compound | LE | ΔG (kcal/mol) | Residue Contacts | Zn Contact |
---|---|---|---|---|
Dihydrorobinetin | 0.4313 | −9.489 | Asn471, Gly472, Gly473, Ile474, Tyr475, Ile476, Glu477, His502, Glu503, His506, Gln509, Gly510, Trp518, Tyr524, Glu533, Glu534, Tyr577, Tyr583 | yes |
Myricitrin | 0.2788 | −9.2 | Asp470, Asn471, Gly472, Gly473, Tyr485, Arg487, Ser492, Ile493, Tyr494, Leu499, His502, Glu503, Glu538, Tyr577, Gly578, Ser579, Trp580, Phe582, Tyr583 | no |
Curcumin | 0.3358 | −9.185 | Asn471, Ile474, Tyr475, Ile476, Glu477, Asn478, His506, Gln509, Trp518, Glu533, Glu534, Tyr577 | no |
4′,5-dihiydroxyflavone | 0.4782 | −9.099 | Asn471, Ile474, Tyr475, Ile476, Glu477, His506, Gln509, Gly510, Trp518, Tyr524, Glu533, Glu534 | yes |
Biochanin A | 0.4316 | −9.064 | Asp470, Asn471, Gly473, Ile474, Tyr475, Ile476, Glu477, His506, Gln509, Gly510, Trp518, Tyr524, Glu533, Glu534, Tyr577, Tyr583 | yes |
5-hydroxyflavone (primuletin) | 0.5011 | −9.02 | Asn471, Gly473, Ile474, Tyr475, Ile476, Glu477, Glu503, His506, Gln509, Gly510, Trp518, Tyr524, Glu533 | yes |
Myricetin | 0.3847 | −8.847 | Asn471, Gly473, Ile474, Tyr475, Ile476, Glu477, Glu503, His506, Gln509, Trp518, Tyr524, Glu533, Glu534, Tyr577, Tyr583 | yes |
2′-hydroxychalcone | 0.5184 | −8.813 | Ile474, Tyr475, Ile476, Glu477, His506, Gln509, Gly510, Trp518, Tyr524, Glu533 | no |
Rhein | 0.4139 | −8.692 | Ile474, Tyr475, Ile476, Glu477, Asn478, His506, Trp518, Glu534, Tyr577 | no |
3-hydroxyflavone | 0.468 | −8.424 | Asn471, Gly473, Ile474, Tyr475, Ile476, Glu477, Glu503, His506, Gln509, Gly510, Trp518, Glu533, Glu534, Tyr577 | no |
Piperine | 0.4079 | −8.404 | Asn471, Gly472, Gly473, Ile474, Tyr475, Ile476, Tyr494, Leu499, His502, Glu503, His506, Trp518, Glu534, Glu538, Arg552, Tyr577, Trp580, Tyr583 | yes |
Palmatine | 0.3223 | −8.329 | Asp470, Asn471, Gly473, Ile 474, Tyr475, Ile476, Glu477, Asn478, His506, Met517, Trp518, Gln520, Glu534, Tyr577, Tyr583 | yes |
Capsaicin | 0.3514 | −8.012 | Asn471, Gly472, Gly473, Ile474, Tyr475, Tyr494, Leu499, His502, Glu503, His506, Trp518, Glu534, Glu538, Tyr577, Trp580, Tyr583, Asn584 | yes |
6-Methoxy-1,2,3,4-tetrahydro-9H-pyrido [3,4-b]indole-1-carboxylic acid | 0.4364 | −7.855 | Asn471, Ile474, Tyr475, Ile476, Glu477, His506, Gln509, Gly510, Trp518, Tyr524, Glu533, Glu534, Tyr577, Tyr583 | no |
Juglone | 0.5688 | −7.402 | Ile474, Tyr475, Ile476, Glu477, His506, Gln509, Gly510, Trp518, Glu533, Glu534, Tyr577 | no |
1,10-Phenanthroline | 0.5203 | −7.284 | Asn471, Gly472, Gly473, Tyr494, Leu499, His502, Glu503, Glu538, Trp580, Tyr583 | no |
Citrulline | 0.4984 | −5.981 | Ile474, Tyr475, Ile476, Glu477, His506, Gln509, Gly510, Val514, Trp518, Tyr524, Glu533, Glu534, Tyr577 | no |
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Nitulescu, G.; Mihai, D.P.; Zanfirescu, A.; Stan, M.S.; Gradinaru, D.; Nitulescu, G.M. Discovery of New Microbial Collagenase Inhibitors. Life 2022, 12, 2114. https://doi.org/10.3390/life12122114
Nitulescu G, Mihai DP, Zanfirescu A, Stan MS, Gradinaru D, Nitulescu GM. Discovery of New Microbial Collagenase Inhibitors. Life. 2022; 12(12):2114. https://doi.org/10.3390/life12122114
Chicago/Turabian StyleNitulescu, Georgiana, Dragos Paul Mihai, Anca Zanfirescu, Miruna Silvia Stan, Daniela Gradinaru, and George Mihai Nitulescu. 2022. "Discovery of New Microbial Collagenase Inhibitors" Life 12, no. 12: 2114. https://doi.org/10.3390/life12122114
APA StyleNitulescu, G., Mihai, D. P., Zanfirescu, A., Stan, M. S., Gradinaru, D., & Nitulescu, G. M. (2022). Discovery of New Microbial Collagenase Inhibitors. Life, 12(12), 2114. https://doi.org/10.3390/life12122114