Clindamycin Derivatives: Unveiling New Prospects as Potential Antitumor Agents
Abstract
:1. Introduction
2. Results
2.1. Intersection of Two Clindamycin Derivative Targets
2.2. Screening of the Antibacterial Targets of the Clindamycin Derivatives through the PubChem Database
2.3. Molecular Docking Simulation and Validation
2.4. Stability of the Docked Complexes Studied via MD Simulation
2.5. Binding Force Analysis
2.6. Protein Subcellular Localization
2.7. Biological Evaluation of Compounds
3. Materials and Methods
3.1. Intersection of Two Clindamycin Derivative Targets
3.2. Screening of the Antibacterial Targets of the Clindamycin Derivatives through the PubChem Database
3.3. Molecular Docking Simulation and Validation
3.4. Stability of the Docked Complexes Studied via MD Simulation
3.5. Binding Force Analysis
3.6. Protein Subcellular Localization
3.7. Biological Evaluation of Compounds
4. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Target | Common Name | PDB ID | Uniprot ID | ChEMBL ID | Target Class |
---|---|---|---|---|---|
Serotonin 1a (5-HT1a) receptor | HTR1A | 7E2X | P08908 | CHEMBL214 | Family A G protein-coupled receptor |
C-C chemokine receptor type 1 | CCR1 | 7VL8 | P32246 | CHEMBL2413 | |
Nociceptin receptor | OPRL1 | 4EA3 | P41146 | CHEMBL2014 | |
Serotonin 2a (5-HT2a) receptor | HTR2A | 6WHA, 7VOD, 6A93, 6WGT | P28223 | CHEMBL224 | |
Alpha-1a adrenergic receptor | ADRA1A | 8THK | P35348 | CHEMBL229 | |
Histamine H1 receptor | HRH1 | 3RZE | P35367 | CHEMBL231 | |
C-C chemokine receptor type 3 | CCR3 | 4ZYA, 5XIX | P51677 | CHEMBL3473 | |
Serotonin 1d (5-HT1d) receptor | HTR1D | 7E32 | P28221 | CHEMBL1983 | |
Serotonin 1b (5-HT1b) receptor | HTR1B | 4IAQ | P28222 | CHEMBL1898 | |
Adrenergic receptor beta | ADRB2 | 2RH1 | P07550 | CHEMBL210 | |
Serotonin 4 (5-HT4) receptor | HTR4 | 7XT8 | Q13639 | CHEMBL1875 | |
Alpha-2a adrenergic receptor | ADRA2A | 7W7E | P08913 | CHEMBL1867 |
PDB ID | Lib Dock Score | |
---|---|---|
3 | 3e | |
7VL8 | 127.398 | 126.845 |
4EA3 | 152.611 | 149.226 |
7VOD | 143.659 | 159.64 |
6WHA | 143.333 | 157.689 |
8THK | 157.21 | 160.324 |
5XIX | 107.145 | 127.742 |
7E32 | 118.02 | 115.01 |
6A93 | 106.887 | 159.495 |
4IAQ | 155.758 | 159.28 |
2RH1 | 164.678 | 184.081 |
Compound | Gibbs Free Energy Values | Dissociation Constant |
---|---|---|
3 | −23.8668 | 1108.10 |
3e | −6.2632 | 28.57 |
Drug | Protein | Location (k = 23) | PDB ID |
---|---|---|---|
Compound 3 | Adrenergic receptor beta | 52.2%: plasma membrane | 2RH1 |
26.1%: endoplasmic reticulum | |||
8.7%: vacuolar | |||
4.3%: mitochondrial | |||
4.3%: nuclear | |||
4.3%: Golgi |
Drug | 0 μg/mL | 2.5 μg/mL | 5 μg/mL | 10 μg/mL |
---|---|---|---|---|
Compound 3e | 100 ± 0.05 | 101.57 ± 2.48 | 105.41 ± 1.53 ** | 70.95 ± 2.60 ** |
Compound 3 | 100 ± 0.05 | 69.98 ± 3.51 ** | 64.26 ± 1.18 ** | 41.75 ± 3.27 ** |
5-FU | 100 ± 0.05 | 47.72 ± 3.59 ** | 50.28 ± 3.87 ** | 58.78 ± 6.97 ** |
blank control | 100 ± 0.05 | 100 ± 0.05 | 100 ± 0.05 | 100 ± 0.05 |
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Jia, Y.; Zhang, Y.; Zhu, H. Clindamycin Derivatives: Unveiling New Prospects as Potential Antitumor Agents. Pharmaceuticals 2024, 17, 276. https://doi.org/10.3390/ph17030276
Jia Y, Zhang Y, Zhu H. Clindamycin Derivatives: Unveiling New Prospects as Potential Antitumor Agents. Pharmaceuticals. 2024; 17(3):276. https://doi.org/10.3390/ph17030276
Chicago/Turabian StyleJia, Yiduo, Yinmeng Zhang, and Hong Zhu. 2024. "Clindamycin Derivatives: Unveiling New Prospects as Potential Antitumor Agents" Pharmaceuticals 17, no. 3: 276. https://doi.org/10.3390/ph17030276