Hyperthermia Intensifies α-Mangostin and Synthetic Xanthones’ Antimalignancy Properties
Abstract
:1. Introduction
2. Results and Discussion
2.1. Chemistry
2.2. Novel Xanthone Derivatives’ Cytotoxicity and Hyperthermia Conditions Establishment
2.3. Hyperthermia Increases the Long-Term Cytotoxicity of Novel Xanthone Derivatives
2.4. Hyperthermia Induces Apoptosis
2.5. Hyperthermia Boosts Xanthones’ Anti-Migratory Effects
2.6. Mitochondrial Mass and Membrane Potential
2.7. RNA Extraction and Real-Time RT PCR
3. Materials and Methods
3.1. Chemistry
3.1.1. Chemicals and Equipment
3.1.2. The Synthesis and Characterization of Intermediate Products (1–5)
6-Chloro-9-oxo-9H-xanthene-2-carbonyl chloride (1)
7-Chloro-9-oxo-9H-xanthene-2-carbonyl chloride (2)
2-(Bromomethyl)-4,6-dichloro-9H-xanthen-9-one (4)
3.1.3. The Synthesis of Final Compounds (C1–C8)
Amide Derivatives (C1–C4)
3-(2-Hydroxypropoxy) Amine Xanthone Derivatives (C5–C6)
2-Methyl Amine Xanthone Derivatives (C7–C8)
3.1.4. Characterization Data for Final Compounds (C1–C8)
6-Chloro-2-(morpholine-4-carbonyl)-9H-xanthen-9-one (C1)
6-Chloro-N-(2-morpholinoethyl)-9-oxo-9H-xanthene-2-carboxamide (C2)
6-Chloro-N-(3-morpholinopropyl)-9-oxo-9H-xanthene-2-carboxamide (C3)
7-Chloro-N-(3-morpholinopropyl)-9-oxo-9H-xanthene-2-carboxamide (C4)
(R/S)-3-(2-Hydroxy-3-morpholinopropoxy)-9H-xanthen-9-one Hydrochloride (C5)
(R/S)-3-(2-Hydroxy-3-((3-morpholinopropyl)amino)propoxy)-9H-xanthen-9-one Dihydrochloride (C6)
4,6-Dichloro-2-(((3-morpholinopropyl)amino)methyl)-9H-xanthen-9-one Dihydrochloride (C7)
7-Chloro-2-(((3-morpholinopropyl)amino)methyl)-9H-xanthen-9-one Dihydrochloride (C8)
3.2. Chemicals for Biological Evaluations
3.3. Cell Culture and Treatment Conditions
3.4. Cell Viability Assay
3.5. Clonogenic Assay
3.6. Scratch Assay
3.7. AO/PI, NAO, and JC-1 Staining
3.8. RNA Extraction and Real-Time™ RT PCR
3.9. Statistics
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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Compound No. | TOV-21G GI50 [μM] | SK-OV-3 GI50 [μM] |
---|---|---|
C1 | 15.58 | >150 |
C2 | 126.43 | >150 |
C3 | 134.20 | >150 |
C4 | 101.63 | 141.80 |
C5 | >150 | >150 |
C6 | 82.87 | 87.93 |
C7 | 16.17 | 28.30 |
C8 | 48.34 | 67.37 |
Compound | Synthetic xanthone derivative structures |
C7 | |
C8 | |
Reference compound structures | |
MAG | |
CIS |
TOV-21G | SK-OV-2 | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
GI50 [μM] | GI25 [μM] | GI10 [μM] | GI50 [μM] | GI25 [μM] | GI10 [μM] | ||||||||
24 h | 48 h | 24 h | 48 h | 24 h | 48 h | 24 h | 48 h | 24 h | 48 h | 24 h | 48 h | ||
37 °C | C7 | 16.17 | 15.77 | 10.94 | 11.01 | 7.81 | 8.16 | 28.30 | 16.35 | 18.03 | 10.63 | 11.87 | 7.19 |
C8 | 48.34 | 32.20 | 23.01 | 19.75 | 7.81 | 12.28 | 67.37 | 53.13 | 45.12 | 33.21 | 31.78 | 21.26 | |
MAG | 10.24 | 10.85 | 5.24 | 6.16 | 2.25 | 3.66 | 67.31 | 38.84 | 50.25 | 32.62 | 40.02 | 28.89 | |
CIS | 46.56 | 54.22 | 31.51 | 28.46 | 22.49 | 13.01 | 27.30 | 9.91 | 12.00 | 5.33 | 2.82 | 2.58 | |
39 °C | C7 | 25.14 | 16.16 | 13.39 | 9.65 | 6.34 | 5.74 | 27.08 | 26.19 | 15.43 | 15.15 | 8.41 | 8.53 |
C8 | 49.04 | 22.77 | 24.22 | 15.41 | 9.32 | 10.98 | 59.18 | 52.59 | 27.45 | 25.13 | 8.45 | 8.65 | |
MAG | 33.72 | 24.27 | 21.56 | 18.94 | 14.27 | 15.75 | 38.53 | 37.22 | 28.38 | 29.97 | 22.29 | 25.62 | |
CIS | 65.11 | 20.21 | 26.28 | 11.91 | 2.98 | 6.93 | 99.86 | 37.13 | 38.10 | 18.46 | 1.05 | 7.25 |
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Rech, J.; Żelaszczyk, D.; Marona, H.; Gunia-Krzyżak, A.; Żmudzki, P.; Bednarek, I.A. Hyperthermia Intensifies α-Mangostin and Synthetic Xanthones’ Antimalignancy Properties. Int. J. Mol. Sci. 2024, 25, 8874. https://doi.org/10.3390/ijms25168874
Rech J, Żelaszczyk D, Marona H, Gunia-Krzyżak A, Żmudzki P, Bednarek IA. Hyperthermia Intensifies α-Mangostin and Synthetic Xanthones’ Antimalignancy Properties. International Journal of Molecular Sciences. 2024; 25(16):8874. https://doi.org/10.3390/ijms25168874
Chicago/Turabian StyleRech, Jakub, Dorota Żelaszczyk, Henryk Marona, Agnieszka Gunia-Krzyżak, Paweł Żmudzki, and Ilona Anna Bednarek. 2024. "Hyperthermia Intensifies α-Mangostin and Synthetic Xanthones’ Antimalignancy Properties" International Journal of Molecular Sciences 25, no. 16: 8874. https://doi.org/10.3390/ijms25168874