Anticancer and Antibacterial Activity Studies of Gold(I)-Alkynyl Chromones
Abstract
:1. Introduction
2. Results and Discussion
2.1. Synthesis of Complexes 4–6
2.2. X-ray Diffraction Study of Compounds
Compound | 5 | 6A | 6B |
---|---|---|---|
Interatomic Distances (Å) | |||
Au-C | 1.996(4) | 1.989(5) | 1.988(4) |
Au-P | 2.2787(10) | 2.2739(12) | 2.2720(11) |
C≡C | 1.205(6) | 1.214(6) | 1.199(6) |
Angles (°) | |||
P-Au-C | 178.13(14) | 174.00(12) | 172.46(12) |
Au-C≡C | 176.5(4) | 164.3(4) | 165.9(4) |
2.3. Biological Results
2.3.1. Antiproliferative Effect toward Human Cancer Cells
Cell Line | IC50 (µmol/L) | |||
---|---|---|---|---|
4 | 5 | 6 | Auranofin | |
HepG2 | 10.0 ± 1.3 | >120 | 19.5 ± 1.9 | 50.0 ± 2.7 |
MCF-7 | 5.5 ± 0.7 | 11.0 ± 0.8 | 13.0 ± 2.3 | 13.1 ± 0.9 |
MDA-MB-231 | 9.7 ± 2.5 | 49.7 ± 1,7 | 10.0 ± 3.4 | 3.0 ± 0.6 |
CCRF-CEM | 3.5 ± 1.1 | 3.8 ± 0.9 | 4.2 ± 0.9 | 6.0 ± 1.2 |
2.3.2. Cellular Uptake with High-Resolution Continuum-Source Atomic Absorption Spectroscopy
2.3.3. TrxR Inhibition Assay
2.3.4. DNA Comet Assay
2.3.5. Cell Cycle Analysis
Cell Line | Cell Cycle Analysis Of DNA Histograms (Sub-G1 Fraction) | |||
---|---|---|---|---|
Control (Untreated Cell) | Compound | |||
4 | 5 | 6 | ||
HepG2 | 1.95 ± 0.23 | 15.31 ± 1.64 * | - | 12.46 ± 1 * |
MDA-MB-231 | 2.39 ± 0.64 | 13.32 ± 1.39 * | - | 5.0 ± 2.51 |
CCRF-CEM | 2.81 ± 0.51 | 13.33 ± 1.37 * | 6.18 ± 1.1 | 9.64 * ± 1.12 |
MCF-7 | 2.87 ± 0.9 | 18.58 ± 2.27 * | 9.42 ± 1 * | 10.48 ± 0.6 * |
2.3.6. Caspase Activation Assay
2.3.7. Evaluation of Antibacterial and Hemolytic Activity
Microorganism | MIC (μg/mL) | |||
---|---|---|---|---|
4 | 5 | 6 | Au(PPh3)Cl | |
S. aureus subsp. aureus ATCC® 29213™ (MSSA) | 4 | 4 | 32 | 2 |
S. aureus subsp. aureus ATCC® 43300 (MRSA) | 2 | 2 | 2 | 1 |
E. coli ATCC® 25922 | >256 | >256 | >256 | 16 |
E. coli ATCC®BAA-198 | >256 | >256 | >256 | 32 |
Clinical isolates: S. aureus | ||||
(MSSA) 26/11 | 4 | 4 | 32 | 2 |
(MSSA) 30/11 | 4 | 4 | 32 | 2 |
(MRSA) 7/10 | 4 | 4 | 16 | 2 |
(MRSA) 41/12 | 4 | 4 | 32 | 2 |
3. Experimental Section
3.1. General Information
3.2. Chemistry
3.2.1. Synthesis of 4
3.2.2. Synthesis of 5
3.2.3. Synthesis of 6
3.3. X-ray Crystallography
3.4. Biology
3.4.1. Cell Lines
3.4.2. Cell Culture
3.4.3. Evaluation of Cytotoxic Activity (MTT Assay)
3.4.4. Thioredoxin Reductase Inhibition Assay
3.4.5. DNA Comet Assay
3.4.6. Cell Cycle Analysis
3.4.7. Caspases Activation Assay
Caspase-8 and Caspase-9 Activities
Caspase-3 Activity
3.4.8. Statistical Analysis
3.4.9. Cellular Uptake and AAS Measurements
Antibacterial Activity
Hemolysis
4. Conclusions
Supplementary Materials
Acknowledgments
Author Contributions
Conflicts of Interest
References and Notes
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Hikisz, P.; Szczupak, Ł.; Koceva-Chyła, A.; Guśpiel, A.; Oehninger, L.; Ott, I.; Therrien, B.; Solecka, J.; Kowalski, K. Anticancer and Antibacterial Activity Studies of Gold(I)-Alkynyl Chromones. Molecules 2015, 20, 19699-19718. https://doi.org/10.3390/molecules201119647
Hikisz P, Szczupak Ł, Koceva-Chyła A, Guśpiel A, Oehninger L, Ott I, Therrien B, Solecka J, Kowalski K. Anticancer and Antibacterial Activity Studies of Gold(I)-Alkynyl Chromones. Molecules. 2015; 20(11):19699-19718. https://doi.org/10.3390/molecules201119647
Chicago/Turabian StyleHikisz, Paweł, Łukasz Szczupak, Aneta Koceva-Chyła, Adam Guśpiel, Luciano Oehninger, Ingo Ott, Bruno Therrien, Jolanta Solecka, and Konrad Kowalski. 2015. "Anticancer and Antibacterial Activity Studies of Gold(I)-Alkynyl Chromones" Molecules 20, no. 11: 19699-19718. https://doi.org/10.3390/molecules201119647