In Silico Identification and In Vitro Evaluation of New ABCG2 Transporter Inhibitors as Potential Anticancer Agents
Abstract
:1. Introduction
2. Results
2.1. In-Silico Analysis
2.2. Biological Investigation
2.3. HepG2 Spheroid Production and Mitoxantrone Treatment
2.4. Effect of the Inhibitor (8) on MTX Uptake in HepG2 Spheroids
3. Discussion
4. Materials and Methods
4.1. Computational Details
4.2. Chemistry
4.3. 2D Cell Cultures and Transfection
4.4. 2D Cell Viability Assay
4.5. Hoechst 33,342 Accumulation Assay
4.6. Mitoxantrone and Inhibitor Treatment on 2D Cell Cultures
4.7. Drug Affinity Responsive Target Stability (DARTS) and Target Identification
4.8. Selectivity Assay
4.9. Spheroids Generation
4.10. Mitoxantrone and Inhibitor Treatment
4.11. 3D Cell Viability Assay
4.12. HEK293 Transfection and Mass Cell Analysis for Gene Expression Confirmation
4.13. Statistical Analysis
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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EC50 ± SD (µM) | |||
---|---|---|---|
Compound | Hep G2 | MCF7 | MCF 10A |
8 | >100 | >100 | >100 |
13a | >100 | >100 | >100 |
30 | 28.21 ± 3.17 | 33.25 ± 2.63 | 36.12 ± 5.46 |
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Di Micco, S.; Di Sarno, V.; Rossi, M.; Vestuto, V.; Konno, T.; Novi, S.; Tecce, M.F.; Napolitano, V.; Ciaglia, T.; Vitale, A.; et al. In Silico Identification and In Vitro Evaluation of New ABCG2 Transporter Inhibitors as Potential Anticancer Agents. Int. J. Mol. Sci. 2023, 24, 725. https://doi.org/10.3390/ijms24010725
Di Micco S, Di Sarno V, Rossi M, Vestuto V, Konno T, Novi S, Tecce MF, Napolitano V, Ciaglia T, Vitale A, et al. In Silico Identification and In Vitro Evaluation of New ABCG2 Transporter Inhibitors as Potential Anticancer Agents. International Journal of Molecular Sciences. 2023; 24(1):725. https://doi.org/10.3390/ijms24010725
Chicago/Turabian StyleDi Micco, Simone, Veronica Di Sarno, Martina Rossi, Vincenzo Vestuto, Takumi Konno, Sara Novi, Mario Felice Tecce, Valeria Napolitano, Tania Ciaglia, Andrea Vitale, and et al. 2023. "In Silico Identification and In Vitro Evaluation of New ABCG2 Transporter Inhibitors as Potential Anticancer Agents" International Journal of Molecular Sciences 24, no. 1: 725. https://doi.org/10.3390/ijms24010725