Mechanism of Anti-Trypanosoma cruzi Action of Gold(I) Compounds: A Theoretical and Experimental Approach
Abstract
:1. Introduction
2. Results and Discussion
2.1. Theoretical Calculations
Natural Bond Orbital (NBO) Analysis
2.2. Cyclic Voltammetry
2.3. Electron Spin Resonance
2.4. Lipophilicity
2.5. Biological Studies: Anti-Trypanosoma Cruzi Activity and Cytotoxicity on Mammalian Cells Models
2.6. Insights into the Mechanism of Action: Production of Free Radical Species and Reactive Oxygen Species on Trypanosoma cruzi
3. Materials and Methods
3.1. Theoretical Calculations
3.2. Electrochemical Studies
3.3. ESR Spectroscopy
3.4. Lipophilicity
3.5. Biological Studies
3.5.1. Viability on T. cruzi (Dm28c) Trypomastigotes
3.5.2. Cytotoxicity on Endothelial Mammalian Cells
3.6. Insight into the Mechanism of Action
3.6.1. Generation of Free Radical Species in T. cruzi
3.6.2. Intraparasitic Reactive Oxygen Species (ROS)
4. Conclusions
Supplementary Materials
Author Contributions
Funding
Data Availability Statement
Conflicts of Interest
References
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Spin | Donor (L) NBO 1 | Acceptor (NL) NBO 2 | E(2) 3 kcal/mol | ||
---|---|---|---|---|---|
α | 32. | LP (1) N 11 | 93. | BD*(1) C 10–N 9 | 73.13 |
α | 34. | LP (2) S 12 | 93. | BD*(1) C 10–N 9 | 33.07 |
α | 43. | LP (4) Cl 14 | 99. | BD*(1) S 12–Au 13 | 75.17 |
β | 30. | LP (1) N 6 | 99. | BD*(1) O 15–O 16 | 1075.57 |
β | 32. | LP (1) N 9 | 93. | BD*(1) C 10–N 11 | 68.87 |
β | 34. | LP (2) S 12 | 93. | BD*(1) C 10–N 11 | 35.94 |
β | 43. | LP (4) Cl 14 | 98. | BD*(1) S 12–Au 13 | 75.13 |
Compound | Couple I | Couple II | Couple III | ||
---|---|---|---|---|---|
Epc 1 | Epa 2 | Epc 1 | Ep 2 | Epc | |
[AuCl(HL1)] | −0.80 | - | −0.96 (−0.92) | −0.89 (−0.80) | −1.38 |
[AuCl(HL2)] | −0.80 | −0.73 | −0.95 (−0.98) | −0.89 (−0.85) | −1.39 |
[AuCl(HL3)] | −0.79 | −0.72 | −0.93 (−0.95) | −0.87 (−0.84) | −1.35 |
[AuCl(HL4)] | −0.75 | −0.74 | −0.92 (−0.92) | −0.86 (−0.81) | −1.38 |
Nifurtimox | - | - | −1.18 | −1.12 | - |
[AuCl(HL1)] | [AuCl(HL2)] | [AuCl(HL3)] | [AuCl(HL4)] | |||||
---|---|---|---|---|---|---|---|---|
Spin Density | a (G) | Spin Density | a (G) | Spin Density | a (G) | Spin Density | a (G) | |
N6 | 0.202404 | 8.55 | 0.199949 | 9.16 | 0.200306 | 9.05 | 0.196242 | 8.20 |
H17 | 0.000468 | 5.20 | 0.000456 | 5.42 | 0.000462 | 5.43 | 0.00043 | 5.10 |
H18 | −0.000346 | 3.28 | −0.000343 | 3.35 | −0.000348 | 3.30 | −0.000338 | 3.40 |
H19 | −0.000119 | 0.83 | −0.000103 | 0.53 | −0.000107 | 0.96 | −0.000087 | 0.90 |
N8 | 0.149215 | 1.09 | 0.15112 | 1.07 | 0.150759 | 1.05 | 0.152195 | 1.07 |
N9 | 0.003226 | 0.88 | 0.002067 | 0.98 | 0.002081 | 0.94 | 0.000466 | 0.90 |
H20 | −0.000051 | 0.67 | −0.000031 | 0.46 | −0.000034 | 0.80 | −0.000061 | 0.90 |
N11 | 0.00880 | - | 0.012168 | - | 0.012004 | - | 0.00945 | - |
H21 | 0.000103 | - | −0.000003 | - | −0.000012 | - | 0.000026 | - |
Compound | T. cruzi IC50/μM | EA.hy926 IC50/μM | SI 1 | RM 3 |
---|---|---|---|---|
[AuCl(HL1)] (1) | 24.5 ± 1.4 | 108.2 ± 6.6 | 4 | −0.22 |
HL1 | 9.8 ± 1.5 2 | >100 2 | >10 | −0.31 |
[AuCl(HL2)] (2) | 10.3 ± 1.0 | 94.0 ± 1.7 | 9 | −0.01 |
HL2 | 17.4 ± 1.9 2 | >100 2 | >6 | −0.04 |
[AuCl(HL3)] (3) | 9.9 ± 1.9 | 46.7 ± 0.7 | 5 | 0.13 |
HL3 | 18.5 ± 1.7 2 | >100 2 | >5 | 0.12 |
[AuCl(HL4)] (4) | 49.1 ± 7.3 | 78.4 ± 2.1 | 2 | 0.17 |
HL4 | 22.7 ± 1.6 2 | >100 2 | >4 | 0.29 |
Nifurtimox | 10.0 ± 0.4 | >200 | >20 | 0.02 |
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Órdenes-Rojas, J.; Risco, P.; Ortega-Campos, J.; Barriga-González, G.; Liempi, A.; Kemmerling, U.; Gambino, D.; Otero, L.; Olea Azar, C.; Rodríguez-Arce, E. Mechanism of Anti-Trypanosoma cruzi Action of Gold(I) Compounds: A Theoretical and Experimental Approach. Inorganics 2024, 12, 133. https://doi.org/10.3390/inorganics12050133
Órdenes-Rojas J, Risco P, Ortega-Campos J, Barriga-González G, Liempi A, Kemmerling U, Gambino D, Otero L, Olea Azar C, Rodríguez-Arce E. Mechanism of Anti-Trypanosoma cruzi Action of Gold(I) Compounds: A Theoretical and Experimental Approach. Inorganics. 2024; 12(5):133. https://doi.org/10.3390/inorganics12050133
Chicago/Turabian StyleÓrdenes-Rojas, Javiera, Paola Risco, José Ortega-Campos, Germán Barriga-González, Ana Liempi, Ulrike Kemmerling, Dinorah Gambino, Lucía Otero, Claudio Olea Azar, and Esteban Rodríguez-Arce. 2024. "Mechanism of Anti-Trypanosoma cruzi Action of Gold(I) Compounds: A Theoretical and Experimental Approach" Inorganics 12, no. 5: 133. https://doi.org/10.3390/inorganics12050133
APA StyleÓrdenes-Rojas, J., Risco, P., Ortega-Campos, J., Barriga-González, G., Liempi, A., Kemmerling, U., Gambino, D., Otero, L., Olea Azar, C., & Rodríguez-Arce, E. (2024). Mechanism of Anti-Trypanosoma cruzi Action of Gold(I) Compounds: A Theoretical and Experimental Approach. Inorganics, 12(5), 133. https://doi.org/10.3390/inorganics12050133