Synthesis, Characterization, and Preliminary In Vitro Cytotoxic Evaluation of a Series of 2-Substituted Benzo [d] [1,3] Azoles
Abstract
:1. Introduction
2. Results and Discussion
2.1. Synthesis and Characterization
2.2. Preliminary In Vitro Antiproliferative Screening
2.3. Molecular Docking Studies
3. Materials and Methods
3.1. Reagents and Apparatus
3.2. Synthesis of 2-Substituted Benzo[d] [1,3] Azole Heterocycle Derivatives (BTA-1, BZM-2, BOX-3, BTA-4, BZM-5, and BOX-6)
3.3. Biological Evaluation
3.4. Methodology and Computational Details
4. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Sample Availability
References
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| ||||
---|---|---|---|---|
Entry | 2-Mercaptobenzo [d] Azole | Br-R | Product | Yield (%) a |
1 | | | | 70 |
2 | | | | 83 |
3 | | | | 80 |
4 | | | | 75 |
5 | | | | 70 |
6 | | | | 77 |
| ||||||||||
---|---|---|---|---|---|---|---|---|---|---|
Comp. | H4 | H5 | H6 | H7 | H8 | H10 | H11 | H13 | H15a | H15b |
BTA-1 | 7.89 | 7.44–7.25a | 7.44–7.25a | 7.73 | 4.58 | 7.40–7.38 | 7.35–7.36 | 6.68 | 5.72 | 5.23 |
BZM-2 | 7.43–7.40 | 7.12–7.08 | 7.12–7.08 | 7.43–7.40 | 4.38 | 7.12–7.08 | 7.12–7.08 | 6.51 | 5.57 | 5.10 |
BOX-3 | 7.62 | 7.30–7.20 | 7.30–7.20 | 7.44–7.43 | 4.54 | 7.41–7.40 | 7.37–7.36 | 6.68 | 5.73 | 5.24 |
BTA-4 | 7.68 | 7.36–7.31 | 7.24–7.19 | 7.67 | 3.92 | − | − | 6.01–5.88 | 5.30 | 5.13 |
BZM-5 | 7.47–7.37 | 7.12–7.04 | 7.12–7.04 | 7.47–7.37 | 3.87 | − | − | 5.97–5.83 | 5.18 | 5.01 |
BOX-6 | 7.60 | 7.29–7.21 | 7.29–7.21 | 7.43 | 3.95 | − | − | 6.08–6.00 | 5.39 | 5.21 |
Compound | U-251 | PC-3 | K-562 | HTC-15 | MCF-7 | SKLU-1 | FGH |
---|---|---|---|---|---|---|---|
| 15.7 | 12.7 | 14.6 | 14.0 | 21.4 | 38.4 | NA |
| 27.5 | 47.0 | 37.2 | 31.2 | 46.8 | 41 | 7.7 |
| NA | NA | NA | 1.1 | 16.7 | 10.4 | NA |
| NA | 2.5 | NA | 5.8 | 4.0 | 12.4 | NA |
| NA | NA | NA | NA | 10.3 | 12.1 | 12.0 |
| NA | NA | NA | NA | 2.5 | 3.2 | NA |
| 80.6 | 36.3 | 54.3 | 58.8 | 71.3 | 43.3 | 100 |
Compound | Receptor | Binding Energy (kcal/mol) AD4 | Binding Energy (kcal/mol) Vina | Binding Energy (kcal/mol) Smina | Mean RMSD (A°) |
---|---|---|---|---|---|
AEE788 | EGFR | −6.7 | −8.3 | −6.7 | 0.845 |
TAM | Erα | −8.1 | −6.2 | −7.9 | 0.568 |
Ulipristal acetate | Pr | −9.4 | −8.5 | −10.6 | 0.352 |
RAP | mTOR | −15.0 | −9.1 | −6.9 | 0.158 |
Ligand | EGFR | Erα | Pr | mTOR | LogP ± 0.47 |
---|---|---|---|---|---|
BTA-1 | 3 | 4 | 5 | 4 | 6.04 |
BZM-2 | 4 | 2 | 4 | 3 | 4.60 |
BOX-3 | 5 | 3 | 3 | 5 | 4.67 |
BTA-4 | 6 | 5 | 6 | 6 | 4.25 |
BZM-5 | 7 | 5 | 7 | 7 | 2.82 |
BOX-6 | 8 | 6 | 7 | 7 | 2.86 |
TAM | 1 | 1 * | 2 | 2 | 6.07 |
Reference ligand (crystal structure) | 2 | 1 | 1 | 1 |
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Linares-Anaya, O.; Avila-Sorrosa, A.; Díaz-Cedillo, F.; Gil-Ruiz, L.Á.; Correa-Basurto, J.; Salazar-Mendoza, D.; Orjuela, A.L.; Alí-Torres, J.; Ramírez-Apan, M.T.; Morales-Morales, D. Synthesis, Characterization, and Preliminary In Vitro Cytotoxic Evaluation of a Series of 2-Substituted Benzo [d] [1,3] Azoles. Molecules 2021, 26, 2780. https://doi.org/10.3390/molecules26092780
Linares-Anaya O, Avila-Sorrosa A, Díaz-Cedillo F, Gil-Ruiz LÁ, Correa-Basurto J, Salazar-Mendoza D, Orjuela AL, Alí-Torres J, Ramírez-Apan MT, Morales-Morales D. Synthesis, Characterization, and Preliminary In Vitro Cytotoxic Evaluation of a Series of 2-Substituted Benzo [d] [1,3] Azoles. Molecules. 2021; 26(9):2780. https://doi.org/10.3390/molecules26092780
Chicago/Turabian StyleLinares-Anaya, Ozvaldo, Alcives Avila-Sorrosa, Francisco Díaz-Cedillo, Luis Ángel Gil-Ruiz, José Correa-Basurto, Domingo Salazar-Mendoza, Adrian L. Orjuela, Jorge Alí-Torres, María Teresa Ramírez-Apan, and David Morales-Morales. 2021. "Synthesis, Characterization, and Preliminary In Vitro Cytotoxic Evaluation of a Series of 2-Substituted Benzo [d] [1,3] Azoles" Molecules 26, no. 9: 2780. https://doi.org/10.3390/molecules26092780