Synthesis, Anticancer Activity and Molecular Docking Studies of Novel N-Mannich Bases of 1,3,4-Oxadiazole Based on 4,6-Dimethylpyridine Scaffold
Abstract
:1. Introduction
2. Results and Discussion
2.1. Chemistry
2.2. Biological Tests
2.2.1. MTT Cell Viability Assay
2.2.2. Clonogenic Assay
2.2.3. Population Doubling Time
2.2.4. Cell Death Detection by Comet Assay
2.2.5. Fluorescent Staining of Actin Filaments
2.3. Molecular Docking Studies
3. Materials and Methods
3.1. Chemistry
3.1.1. Instruments and Chemicals
3.1.2. Preparation and Experimental Properties of Compounds 3–12
3.2. Biological Section
3.2.1. Cell Lines
3.2.2. MTT Cell Viability Assay
3.2.3. Clonogenic Assay
3.2.4. Population Doubling Time
3.2.5. Cell Death Evaluation by Neutral Comet Assay
3.2.6. Fluorescent Staining of Actin Filaments
3.3. Molecular Modeling—Computational Methodology
4. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Acknowledgments
Conflicts of Interest
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Cell Line | IC50 [µM] of Compound 5 | IC50 [µM] of Compound 6 | IC50 [µM] of Cisplatin |
---|---|---|---|
A375 | 80.79 ± 4.85 | 202.47 ± 10.12 | 15.98 ± 3.31 * |
C32 | 170.28 ± 10.22 | 304.39 ± 15.21 | 9.79 ± 1.51 * |
SNB-19 | 126.02 ± 7.56 | 295.81 ± 14.71 | 43.47 [48] |
MCF-7/WT | 119.29 ± 7.16 | 261.40 ± 13.07 | 5.75 ± 0.02 [49] |
MCF-7/DOX | 137.31 ± 8.24 | 295.81 ± 14.92 | 47.82 ± 2.45 * |
HaCaT | 115.12 ± 6.91 | 270.32 ± 13.25 | 56.00 ± 7.27 [50] |
Compound | cMET | EGRF | HER2 | hTrkA |
---|---|---|---|---|
3 | −11.8 | −12.0 | −12.2 | −13.2 |
4 | −12.1 | −11.8 | −12.9 | −13.4 |
5 | −12.1 | −12.2 | −12.5 | −13.6 |
6 | −11.4 | −11.4 | −12.1 | −13.2 |
7 | −11.9 | −12.9 | −13.6 | −14.0 |
8 | −11.6 | −10.8 | −11.8 | −13.7 |
9 | −9.7 | −11.0 | −10.3 | −11.7 |
10 | −11.1 | −11.4 | −12.2 | −13.6 |
11 | −12.6 | −12.0 | −12.3 | −14.5 |
12 | −10.6 | −11.1 | −11.2 | −13.5 |
Erlotinib | −9.2 | −10.9 | −10.5 | −10.4 |
Neratinib | −12.3 | −13.1 | −13.2 | −14.2 |
Tepotinib | −13.7 | −13.9 | −13.5 | −14.2 |
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Strzelecka, M.; Glomb, T.; Drąg-Zalesińska, M.; Kulbacka, J.; Szewczyk, A.; Saczko, J.; Kasperkiewicz-Wasilewska, P.; Rembiałkowska, N.; Wojtkowiak, K.; Jezierska, A.; et al. Synthesis, Anticancer Activity and Molecular Docking Studies of Novel N-Mannich Bases of 1,3,4-Oxadiazole Based on 4,6-Dimethylpyridine Scaffold. Int. J. Mol. Sci. 2022, 23, 11173. https://doi.org/10.3390/ijms231911173
Strzelecka M, Glomb T, Drąg-Zalesińska M, Kulbacka J, Szewczyk A, Saczko J, Kasperkiewicz-Wasilewska P, Rembiałkowska N, Wojtkowiak K, Jezierska A, et al. Synthesis, Anticancer Activity and Molecular Docking Studies of Novel N-Mannich Bases of 1,3,4-Oxadiazole Based on 4,6-Dimethylpyridine Scaffold. International Journal of Molecular Sciences. 2022; 23(19):11173. https://doi.org/10.3390/ijms231911173
Chicago/Turabian StyleStrzelecka, Małgorzata, Teresa Glomb, Małgorzata Drąg-Zalesińska, Julita Kulbacka, Anna Szewczyk, Jolanta Saczko, Paulina Kasperkiewicz-Wasilewska, Nina Rembiałkowska, Kamil Wojtkowiak, Aneta Jezierska, and et al. 2022. "Synthesis, Anticancer Activity and Molecular Docking Studies of Novel N-Mannich Bases of 1,3,4-Oxadiazole Based on 4,6-Dimethylpyridine Scaffold" International Journal of Molecular Sciences 23, no. 19: 11173. https://doi.org/10.3390/ijms231911173
APA StyleStrzelecka, M., Glomb, T., Drąg-Zalesińska, M., Kulbacka, J., Szewczyk, A., Saczko, J., Kasperkiewicz-Wasilewska, P., Rembiałkowska, N., Wojtkowiak, K., Jezierska, A., & Świątek, P. (2022). Synthesis, Anticancer Activity and Molecular Docking Studies of Novel N-Mannich Bases of 1,3,4-Oxadiazole Based on 4,6-Dimethylpyridine Scaffold. International Journal of Molecular Sciences, 23(19), 11173. https://doi.org/10.3390/ijms231911173