New-Generation Heterocyclic Bis-Pentamethinium Salts as Potential Cytostatic Drugs with Dual IL-6R and Mitochondria-Targeting Activity
Abstract
:1. Introduction
2. Materials and Methods
2.1. Synthesis of Bis-Pentamethinium Salts
2.2. Analytical Studies
2.3. Photostability Assay
2.4. In Silico Docking of Bis-Pentamethinium Salts 5 and 6 to the IL-6R Model
2.5. Microscale Thermophoresis (MST)
2.6. Cell Lines and Cell Culture
2.7. Cytotoxicity Assays
2.8. Intracellular Studies of Bis-Pentamethinium Salts
2.9. Colocalization Analysis
2.10. Mitochondrial Respiration
2.11. Inhibitory Effect of Bis-PMSs 5 a 6 on STAT3 Activation in a HEK Reporter Cell Line
3. Results and Discussion
3.1. Synthesis of Bis-Pentamethinium Salts
3.2. Photophysical Characteristics
3.3. In Silico Docking of Bis-Pentamethinium Salts 5 and 6 to the IL-6R Model
3.4. Interaction of Bis-Pentamethinium Salts 5 and 6 with IL-6R
3.5. Cytotoxicity Assays
3.6. Influence of Bis-Pentamethinium Salts 5 and 6 on Mitochondrial Morphology and Function
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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Cell Lines | Bis-PMS 5 | Bis-PMS 6 | ||
---|---|---|---|---|
Mean (µM) | SD | Mean (µM) | SD | |
HFP4 | 0.987 | 0.575 | 1.499 | 0.452 |
BJ-hTERT | 1.660 | 0.038 | 1.218 | 0.442 |
BLM | 0.300 | 0.117 | 1.419 | 0.486 |
A2058 | 0.287 | 0.109 | 0.636 | 0.359 |
H1299 | 2.755 | 0.063 | 0.169 | 0.031 |
BT-20 | 0.701 | 0.228 | 0.779 | 0.160 |
U2-OS | 0.496 | 0.145 | 0.242 | 0.092 |
U251 | 0.719 | 0.219 | 0.505 | 0.020 |
Gl261 | 0.971 | 0.079 | 0.268 | 0.050 |
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Talianová, V.; Kejík, Z.; Kaplánek, R.; Veselá, K.; Abramenko, N.; Lacina, L.; Strnadová, K.; Dvořánková, B.; Martásek, P.; Masařík, M.; et al. New-Generation Heterocyclic Bis-Pentamethinium Salts as Potential Cytostatic Drugs with Dual IL-6R and Mitochondria-Targeting Activity. Pharmaceutics 2022, 14, 1712. https://doi.org/10.3390/pharmaceutics14081712
Talianová V, Kejík Z, Kaplánek R, Veselá K, Abramenko N, Lacina L, Strnadová K, Dvořánková B, Martásek P, Masařík M, et al. New-Generation Heterocyclic Bis-Pentamethinium Salts as Potential Cytostatic Drugs with Dual IL-6R and Mitochondria-Targeting Activity. Pharmaceutics. 2022; 14(8):1712. https://doi.org/10.3390/pharmaceutics14081712
Chicago/Turabian StyleTalianová, Veronika, Zdeněk Kejík, Robert Kaplánek, Kateřina Veselá, Nikita Abramenko, Lukáš Lacina, Karolína Strnadová, Barbora Dvořánková, Pavel Martásek, Michal Masařík, and et al. 2022. "New-Generation Heterocyclic Bis-Pentamethinium Salts as Potential Cytostatic Drugs with Dual IL-6R and Mitochondria-Targeting Activity" Pharmaceutics 14, no. 8: 1712. https://doi.org/10.3390/pharmaceutics14081712