5-Aryl-1-Arylideneamino-1H-Imidazole-2(3H)-Thiones: Synthesis and In Vitro Anticancer Evaluation
Abstract
1. Introduction
2. Result and Discussion
2.1. Chemistry
2.2. In Vitro Antitumor Evaluation
2.2.1. In Vitro Cytotoxic Activity against Three Cancer Cell Lines
2.2.2. Cell Cycle Analysis
2.2.3. Annexin V-FITC/PI Apoptosis Induction Analysis
2.2.4. VEGFR-2 Kinase Inhibitory Activity
2.2.5. B-Raf Ihibitory Activity
2.2.6. Molecular Docking Study
3. Material and Methods
3.1. General
3.2. General Procedure for the Synthesis of 2-Arylhydrazinecarbothioamide (3a–d)
3.2.1. (E)-2-Benzylidenehydrazinecarbothioamide (3a)
3.2.2. (E)-2-(2-Hydroxybenzylidene)hydrazinecarbothioamide (3b)
3.2.3. (E)-2-(4-Methoxybenzylidene)hydrazinecarbothioamide (3c)
3.2.4. (E)-2-((E)-3-Phenylallylidene)hydrazinecarbothioamide (3d)
3.3. General Procedure for the Synthesis of Imidazole Derivatives 4a–e and 5
3.3.1. (E)-1-(Benzylideneamino)-5-(4-chlorophenyl)-1H-imidazole-2(3H)-thione (4a)
3.3.2. (E)-5-(4-Chlorophenyl)-1-(2-hydroxybenzylideneamino)-1H-imidazole-2(3H)-thione (4b)
3.3.3. (E)-1-(5-Bromo-2-hydroxybenzylideneamino)-5-(4-chlorophenyl)-1H-imidazole-2(3H)-thione (4c)
3.3.4. (E)-5-(4-Chlorophenyl)-1-(4-methoxybenzylideneamino)-1H-imidazole-2(3H)-thione (4d)
3.3.5. 5-(4-Chlorophenyl)-1-((E)-((E)-3-phenylallylidene)amino)-1H-imidazole-2(3H)-thione (4e)
3.3.6. (E)-1-(2-Hydroxybenzylideneamino)-5-(4-methoxyphenyl)-1H-imidazole-2(3H)-thione (5)
3.4. General Procedure for the Synthesis (E)-2-((3-Acetyl-5-(4-chlorophenyl)-2-thioxo-2,3-dihydro-1H-imidazol-1-ylimino)methyl)phenyl Acetate (6)
3.5. Biological Studies
3.5.1. Antitumor Activity against Three Cancer Cell Lines
3.5.2. Cell Cycle Analysis of Compounds 4d and 5
3.5.3. Annexin V FITC/PI Apoptosis Detection Staining Assay
3.5.4. In Vitro VEGFR-2 Kinase Assay
3.5.5. In Vitro B-Raf Kinase Assay
3.6. Molecular Docking Study
4. Conclusions
Supplementary Materials
Author Contributions
Funding
Data Availability Statement
Acknowledgments
Conflicts of Interest
Sample Availability
References
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Comp No. | IC50 (μM) | |||
---|---|---|---|---|
MCF-7 | HepG2 | HCT-116 | MCF-10A | |
4a | >50 | 61.81 ± 4.1 | 20.56 ± 1.4 | NT |
4b | 24.94 ± 1.6 | >50 | 23.53 ± 1.6 | NT |
4c | 43.95 ± 2.9 | 11.36 ± 0.8 | 9.962 ± 0.7 | NT |
4d | 7.967 ± 0.5 | 4.086 ± 0.3 | 28.95 ± 1.9 | 44.06 ± 0.23 |
4e | 13.15 ± 0.9 | 17.01 ± 1.1 | 3.988 ± 0.3 | NT |
5 | 1.071 ± 0.1 | 1.301 ± 0.1 | 3.99 ± 0.3 | 27.81 ± 0.31 |
DOC | 11.09 ± 0.7 | 8.128 ± 0.5 | 13.96 ± 0.9 | 33.17 ± 0.19 |
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Abu Almaaty, A.H.; Toson, E.E.M.; El-Sayed, E.-S.H.; Tantawy, M.A.M.; Fayad, E.; Abu Ali, O.A.; Zaki, I. 5-Aryl-1-Arylideneamino-1H-Imidazole-2(3H)-Thiones: Synthesis and In Vitro Anticancer Evaluation. Molecules 2021, 26, 1706. https://doi.org/10.3390/molecules26061706
Abu Almaaty AH, Toson EEM, El-Sayed E-SH, Tantawy MAM, Fayad E, Abu Ali OA, Zaki I. 5-Aryl-1-Arylideneamino-1H-Imidazole-2(3H)-Thiones: Synthesis and In Vitro Anticancer Evaluation. Molecules. 2021; 26(6):1706. https://doi.org/10.3390/molecules26061706
Chicago/Turabian StyleAbu Almaaty, Ali H., Eslam E. M. Toson, El-Sherbiny H. El-Sayed, Mohamed A. M. Tantawy, Eman Fayad, Ola A. Abu Ali, and Islam Zaki. 2021. "5-Aryl-1-Arylideneamino-1H-Imidazole-2(3H)-Thiones: Synthesis and In Vitro Anticancer Evaluation" Molecules 26, no. 6: 1706. https://doi.org/10.3390/molecules26061706
APA StyleAbu Almaaty, A. H., Toson, E. E. M., El-Sayed, E.-S. H., Tantawy, M. A. M., Fayad, E., Abu Ali, O. A., & Zaki, I. (2021). 5-Aryl-1-Arylideneamino-1H-Imidazole-2(3H)-Thiones: Synthesis and In Vitro Anticancer Evaluation. Molecules, 26(6), 1706. https://doi.org/10.3390/molecules26061706