Combined Effect of Caspase-Dependent and Caspase-Independent Apoptosis in the Anticancer Activity of Gold Complexes with Phosphine and Benzimidazole Derivatives
Abstract
:1. Introduction
2. Results
2.1. Analytical and Spectroscopic Characterization of 1 and 2
2.2. Crystal Structures of Complexes 1 and 2
2.3. Cytotoxicity Studies and Determination of Cell Death Type
3. Discussion
4. Materials and Methods
4.1. Materials
4.2. Physical Measurements
4.3. Synthesis of the Complexes
4.3.1. (Au(pben)(PPh3)) (1)
4.3.2. (Au(pben)(PEt3)) (2)
4.4. Cell Culture
4.5. Cytotoxic Effects
4.6. Flow Cytometry Analysis of Cell Death Type
4.7. Caspase-3 Assay
4.8. Determination of ROS Production
4.9. Statistical Analysis
4.10. Crystallographic Studies
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Bond | Lengths (Å) | Bond | Angles (°) |
---|---|---|---|
Au(1)-N(1) | 2.058(6) | Au(2)-N(4) | 2.060(6) |
Au(1)-P(1) | 2.230(2) | Au(2)-P(2) | 2.235(2) |
Au(1)···N(3) | 2.792(7) | Au(2)···N(6) | 2.782(7) |
N(1)-Au(1)-P(1) | 176.40(18) | N(4)-Au(2)-P(2) | 174.75(18) |
N(1)-Au(1)-N(3) | 68.5(2) | N(4)-Au(2)-N(6) | 68.8(2) |
P(1)-Au(1)-N(3) | 113.52(17) | P(2)-Au(2)-N(6) | 114.48(16) |
C(13)-P(1)-Au(1) | 110.5(3) | C(43)-P(2)-Au(2) | 113.9(3) |
C(25)-P(1)-Au(1) | 115.1(3) | C(49)-P(2)-Au(2) | 108.0(3) |
C(19)-P(1)-Au(1) | 112.9(3) | C(55)-P(2)-Au(2) | 114.9(3) |
C(3)-N(1)-Au(1) | 129.6(6) | C(31)-N(4)-Au(2) | 126.3(5) |
C(1)-N(1)-Au(1) | 125.5(5) | C(33)-N(4)-Au(2) | 128.7(5) |
C(8)-N(3)-Au(1) | 106.2(5) | C(38)-N(6)-Au(2) | 104.7(5) |
C(9)-N(3)-Au(1) | 134.2(7) | C(39)-N(6)-Au(2) | 135.3(6) |
Bond | Lengths (Å) | Bond | Angles (°) |
---|---|---|---|
Au(1)-N(1) | 2.050(6) | Au(2)-N(4) | 2.058(5) |
Au(1)-P(1) | 2.2288(18) | Au(2)-P(2) | 2.224(2) |
Au(1)···N(3) | 2.975(6) | Au(2)···N(6) | 2.849(6) |
N(1)-Au(1)-P(1) | 172.59(16) | N(4)-Au(2)-P(2) | 174.37(17) |
N(1)-Au(1)-N(3) | 66.34(19) | N(4)-Au(2)-N(6) | 67.38(19) |
P(1)-Au(1)-N(3) | 120.75(12) | P(2)-Au(2)-N(6) | 116.88(13) |
Compound | Incubation Time (h) | IC50 (μM) | R2 | 95% Confidence Interval |
---|---|---|---|---|
1 | 6 | 6.2 | 0.97 | 3.851 to 8.30 |
24 | 2.7 | 0.94 | 1.534 to 4.684 | |
2 | 6 | 3.1 | 0.93 | 1.340 to 5.015 |
24 | 1.6 | 0.91 | 0.8094 to 3.018 |
Compound | 1 | 2 |
---|---|---|
Empirical formula | C30H23AuN3P | C18H23AuN3P |
Formula weight | 653.45 | 509.33 |
Temperature (K) | 293(2) | 100(2) |
Wavelength (Å) | 0.71073 | 0.71073 |
Crystal system | Monoclinic | Monoclinic |
Space group | P21/c | P21/n |
a (Å) | 9.4636(5) | 14.6206(10) |
b (Å) | 18.3327(10) | 13.0799(9) |
c (Å) | 32.0984(17) | 20.0179(14) |
α (°) | 90 | 90 |
β (°) | 98.2780(10) | 102.335(2)° |
γ (°) | 90 | 90 |
Volume (Å3) | 5510.8(5) | 3739.8(4) |
Z | 8 | 8 |
Density (calculated) (g cm−3) | 1.575 | 1.809 |
Absorption coefficient (mm−1) | 5.419 | 7.956 |
F(000) | 2544 | 1968 |
Crystal size (mm3) | 0.35 × 0.15 × 0.09 | 0.311 × 0.281 × 0.252 |
Theta range for data collection (°) | 1.70 to 28.01 | 2.485 to 28.423 |
Index ranges | −12 ≤ h ≤ 12, −17 ≤ k ≤ 24, −39 ≤ l ≤ 42 | −19 ≤ h ≤ 19, −17 ≤ k ≤ 17, −25 ≤ l ≤ 26 |
Reflections collected | 30301 | 89059 |
Independent reflections | 12296 | 9338 |
Data/restraints/parameters | 12296/0/631 | 9338/10/444 |
Goodness-of-fit on F2 | 0.805 | 1.140 |
Largest diff. peak and hole (e Å−3) | 1.345 and −1.339 | 4.100 and −5.096 |
Final R indices (I>2sigma(I)) | R1 = 0.0440, wR2 = 0.0875 | R1 = 0.0463, wR2 = 0.0881 |
R indices (all data) | R1 = 0.1218, wR2 = 0.0979 | R1 = 0.0640, wR2 = 0.0997 |
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Rouco, L.; Sánchez-González, Á.; Alvariño, R.; Alfonso, A.; Vázquez-López, E.M.; García-Martínez, E.; Maneiro, M. Combined Effect of Caspase-Dependent and Caspase-Independent Apoptosis in the Anticancer Activity of Gold Complexes with Phosphine and Benzimidazole Derivatives. Pharmaceuticals 2021, 14, 10. https://doi.org/10.3390/ph14010010
Rouco L, Sánchez-González Á, Alvariño R, Alfonso A, Vázquez-López EM, García-Martínez E, Maneiro M. Combined Effect of Caspase-Dependent and Caspase-Independent Apoptosis in the Anticancer Activity of Gold Complexes with Phosphine and Benzimidazole Derivatives. Pharmaceuticals. 2021; 14(1):10. https://doi.org/10.3390/ph14010010
Chicago/Turabian StyleRouco, Lara, Ángeles Sánchez-González, Rebeca Alvariño, Amparo Alfonso, Ezequiel M. Vázquez-López, Emilia García-Martínez, and Marcelino Maneiro. 2021. "Combined Effect of Caspase-Dependent and Caspase-Independent Apoptosis in the Anticancer Activity of Gold Complexes with Phosphine and Benzimidazole Derivatives" Pharmaceuticals 14, no. 1: 10. https://doi.org/10.3390/ph14010010