Design, Synthesis, and Docking Study of Acyl Thiourea Derivatives as Possible Histone Deacetylase Inhibitors with a Novel Zinc Binding Group
Abstract
:1. Introduction
2. Materials and Methods
2.1. Chemical Synthesis (Scheme 1)
2.1.1. General Synthesis of Adipic and Pimelic Anhydrides (4b and 5b)
2.1.2. General Synthesis of Monosodium Adipic Monoanilide and Monosodium Pimelic Monoanilide (4d and 5d)
2.1.3. General Synthesis of Adipic Monoanilide Acid Chloride and Pimelic Monoanilide Acid Chloride (4e and 5e)
2.1.4. General Synthesis of Adipic Monoanilide Isothiocyanate and Pimelic Monoanilide Isothiocyanate (4f and 5f)
2.1.5. General Synthesis of N-Adipoyl Monoanilide Thiourea and N-Pimeloyl Monoanilide Thiourea (4 and 5)
2.2. In Vitro Cytotoxicity Study
2.2.1. Maintenance of Cell Cultures
2.2.2. Cytotoxicity Assay
2.3. Molecular Docking
3. Results and Discussion
3.1. Chemical Synthesis
3.2. Cytotoxicity Study
3.3. Docking Study
4. Conclusions
Supplementary Materials
Author Contributions
Funding
Conflicts of Interest
References
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Isoform/PDB Code | Ligand | Pose Rank | Energy of Binding (Kcal/mol) | Ki | H-Bonds | Distance from Zn+2 (Å) | |||
---|---|---|---|---|---|---|---|---|---|
no. | Involved Ligand Atoms | Involved Residue | Length (Å) | ||||||
HDAC2/4LXZ, chain A | SAHA | 1st | −7.1 | 6.2 × 10−6 | 1 | 1H | Tyr297 | 2.029 | 2O:5.117 |
5O:2.198 | |||||||||
4 | 1st | −7.3 | 4.42 × 10−6 | 4 | 1H | His135 | 2.3 | 2N:2.028 | |
3H | Asp170(OD1) | 2.326 | S:3.890 | ||||||
3H | Asp170(OD2) | 2.165 | 6O:4.278 | ||||||
4H | Asp258 | 2.705 | |||||||
5 | 1st | −7.1 | 6.2 × 10−6 | 1 | 1H | Asp170 | 2.483 | 2N:2.012 | |
S:3.889 | |||||||||
6O:4.247 | |||||||||
HDAC7/3ZNR, chain A | SAHA | 6th | −6.9 | 8.69 × 10−6 | 2 | 5O | His137 | 2.311 | 2O:5.314 |
5O | His136 | 2.180 | 5O:2.224 | ||||||
4 | 3rd | −7.2 | 5.37 × 10−6 | 4 | 1H | Asp174(OD2) | 2.343 | 2N:1.445 | |
1H | Asp174(OD1) | 2.204 | S:3.781 | ||||||
1H | Asp268 | 2.308 | 6O:4.819 | ||||||
6O | His176 | 2.152 | |||||||
5 | 2nd | −7.2 | 5.37 × 10−6 | 3 | 6O | Gly309 | 1.986 | 2N:2.555 | |
1H | His176 | 2.353 | S:3.693 | ||||||
6O:4.267 | |||||||||
S | His136 | 3.176 |
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Al-Amily, D.H.; Hassan Mohammed, M. Design, Synthesis, and Docking Study of Acyl Thiourea Derivatives as Possible Histone Deacetylase Inhibitors with a Novel Zinc Binding Group. Sci. Pharm. 2019, 87, 28. https://doi.org/10.3390/scipharm87040028
Al-Amily DH, Hassan Mohammed M. Design, Synthesis, and Docking Study of Acyl Thiourea Derivatives as Possible Histone Deacetylase Inhibitors with a Novel Zinc Binding Group. Scientia Pharmaceutica. 2019; 87(4):28. https://doi.org/10.3390/scipharm87040028
Chicago/Turabian StyleAl-Amily, Duraid H., and Mohammed Hassan Mohammed. 2019. "Design, Synthesis, and Docking Study of Acyl Thiourea Derivatives as Possible Histone Deacetylase Inhibitors with a Novel Zinc Binding Group" Scientia Pharmaceutica 87, no. 4: 28. https://doi.org/10.3390/scipharm87040028
APA StyleAl-Amily, D. H., & Hassan Mohammed, M. (2019). Design, Synthesis, and Docking Study of Acyl Thiourea Derivatives as Possible Histone Deacetylase Inhibitors with a Novel Zinc Binding Group. Scientia Pharmaceutica, 87(4), 28. https://doi.org/10.3390/scipharm87040028