Naphthoquinone-Quinolone Hybrids with Antitumor Effects on Breast Cancer Cell Lines—From the Synthesis to 3D-Cell Culture Effects
Abstract
:1. Introduction
2. Results and Discussion
2.1. Chemical Synthesis
2.2. Structure Characterization
2.3. Antitumor Effects
2.3.1. Cytotoxicity
2.3.2. Selectivity Indices (SI)
2.3.3. Apoptosis Induction
2.3.4. Clonogenic Assay
2.3.5. Duration and Reversibility of the Effects
2.3.6. 3D-Cell Culture Viability
2.3.7. In Silico Drug-Likeness and ADME
3. Materials and Methods
3.1. Synthesis
3.2. Biological Assays
3.2.1. Cell Lines
3.2.2. MTT Assay
3.2.3. Clonogenic Assay
3.2.4. Apoptosis Assay
3.2.5. 3D-Cell Culture
3.2.6. Acid Phosphatase Assay
3.2.7. In Silico Drug-Likeness and ADME
3.2.8. Statistical Analyses, IC50, and Selectivity Index Calculation
4. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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IC50 ± SEM (µM) | SI | ||||
---|---|---|---|---|---|
Compound | MCF-7 | MDA-MB-231 | MCF10A | IC50 MCF10A/IC50 MCF-7 | IC50 MCF10A/ IC50 MDA-MB-231 |
1,4-Naphthoquinone | 29.52 ± 1.0 | 19.29 ± 1.1 | 8.78 ± 1.1 | 0.30 ± 0.13 | 0.46 ± 0.14 |
11a | 18.65 ± 1.1 | 9.16 ± 1.0 | 10.60 ± 1.2 | 0.57 ± 0.12 | 1.15 ± 0.15 |
11b | 19.45 ± 1.1 | 15.05 ± 1.0 | 10.71 ± 1.3 | 0.55 ± 0.13 | 0.71 ± 0.14 |
11c | 32.84 ± 1.1 | 16.40 ± 1.1 | 10.25 ± 1.1 | 0.31 ± 0.11 | 0.62 ± 0.12 |
11d | 25.14 ± 1.2 | 20.12 ± 1.1 | 21.49 ± 1.2 | 0.85 ± 0.07 | 1.07 ± 0.08 |
11e | ND * | ND * | ND * | ND * | ND * |
11f | 65.70 ± 1.1 | 24.10 ± 1.1 | 6.92 ± 1.1 | 0.11 ± 0.16 | 0.29 ± 0.16 |
Doxorubicin | 14.22 ± 1.1 | 2.76 ± 1.2 | 1.49 ± 1.3 | 0.10 ± 0.09 | 0.54 ± 0.10 |
Compound | MW a | nHA b | nAHA c | nRotB d | nHBA e | nHBD f | MR g | TPSA h | MlogP i | ESOL j |
---|---|---|---|---|---|---|---|---|---|---|
11a | 401.41 | 30 | 16 | 5 | 5 | 0 | 113.44 | 82.44 | 1.75 | MS |
11b | 449.45 | 34 | 22 | 5 | 5 | 0 | 128.71 | 82.44 | 2.63 | MS |
11c | 443.49 | 33 | 16 | 8 | 5 | 0 | 127.86 | 82.44 | 2.37 | MS |
11d | 373.36 | 28 | 16 | 3 | 5 | 1 | 104.32 | 93.44 | 1.33 | MS |
11e | 435.43 | 33 | 22 | 4 | 5 | 1 | 124.0 | 93.44 | 2.16 | MS |
11f | 415.44 | 31 | 16 | 6 | 5 | 1 | 118.74 | 93.44 | 1.96 | MS |
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da Gama Oliveira, V.; Muxfeldt, M.; Muniz da Paz, M.; Silva Coutinho, M.; Eduardo dos Santos, R.; Diniz da Silva Ferretti, G.; Ferraz da Costa, D.C.; Fonseca Regufe, P.; Lelis Gama, I.; da Costa Santos Boechat, F.; et al. Naphthoquinone-Quinolone Hybrids with Antitumor Effects on Breast Cancer Cell Lines—From the Synthesis to 3D-Cell Culture Effects. Int. J. Mol. Sci. 2024, 25, 6490. https://doi.org/10.3390/ijms25126490
da Gama Oliveira V, Muxfeldt M, Muniz da Paz M, Silva Coutinho M, Eduardo dos Santos R, Diniz da Silva Ferretti G, Ferraz da Costa DC, Fonseca Regufe P, Lelis Gama I, da Costa Santos Boechat F, et al. Naphthoquinone-Quinolone Hybrids with Antitumor Effects on Breast Cancer Cell Lines—From the Synthesis to 3D-Cell Culture Effects. International Journal of Molecular Sciences. 2024; 25(12):6490. https://doi.org/10.3390/ijms25126490
Chicago/Turabian Styleda Gama Oliveira, Vanessa, Marcelly Muxfeldt, Mariana Muniz da Paz, Mayra Silva Coutinho, Raissa Eduardo dos Santos, Giulia Diniz da Silva Ferretti, Danielly C. Ferraz da Costa, Pedro Fonseca Regufe, Ivson Lelis Gama, Fernanda da Costa Santos Boechat, and et al. 2024. "Naphthoquinone-Quinolone Hybrids with Antitumor Effects on Breast Cancer Cell Lines—From the Synthesis to 3D-Cell Culture Effects" International Journal of Molecular Sciences 25, no. 12: 6490. https://doi.org/10.3390/ijms25126490