Gold(I) and Silver(I) Complexes Containing Hybrid Sulfonamide/Thiourea Ligands as Potential Leishmanicidal Agents
Abstract
:1. Introduction
2. Materials and Methods
2.1. Materials
2.2. General Methods
2.3. Preparation of the Compounds
2.3.1. Synthesis of HLR Ligands
2.3.2. Synthesis of [Ag(HLR)2]NO3 Complexes
2.3.3. Synthesis of [Au(HLR)2]Cl Complexes
2.4. Crystal Structure Determinations
2.5. Theoretical Calculations
2.5.1. DFT
2.5.2. Molecular Docking
2.6. Biological Studies
2.6.1. Cultivation of the Leishmania infantum and Leishmania braziliensis
2.6.2. Cytotoxicity Assays (Vero Cells Culture)
2.6.3. Infectivity Test
2.7. Enzymatic Studies
2.7.1. Expression and Purification of LbOYE
2.7.2. Suppression of Intrinsic Tryptophan Fluorescence
2.7.3. Enzyme Kinetics
3. Results and Discussion
3.1. Synthesis and Characterization
3.2. Crystal Structures
3.3. Photophysical Studies
3.4. DFT Calculations
3.5. Biological Studies
3.5.1. Cytotoxicity on Vero Cells
3.5.2. Tests against Leishmania infantum and Leishmania braziliensis Parasites
Compound | CC50 (µM) | IC50 (µM) L. braziliensis | IC50 (µM) L. infantum | SI L. infantum | SI L. braziliensis |
---|---|---|---|---|---|
HL1Ch | 293.0 | 128.9 ± 0.051 | 11 ± 0.306 | 26.64 | 2.27 |
HL2Ph | 268.0 | 273.5 ± 0.018 | 48.39 ± 0.189 | 5.54 | 0.98 |
HL3FPh | 291.8 | 204.5 ± 0.018 | 201.2 ± 0.052 | 1.450 | 1.43 |
HL4ClPh | 16.80 | 133.8 ± 0.036 | 108.4 ± 0.104 | 0.16 | 0.13 |
HL5NO2Ph | 26.62 | 19.02 ± 0.012 | 286.9 ± 0.075 | 0.09 | 1.40 |
HL6Al | 187.9 | 313.5 ± 0.063 | 812.8 ± 0.515 | 0.23 | 0.60 |
Ag1 | 7.400 | 50.15 ± 0.020 | 57.42 ± 0.028 | 0.129 | 0.15 |
Ag2 | 92.14 | 183.7 ± 0.027 | 280.5 ± 0.167 | 0.33 | 0.50 |
Ag3 | >500 | 233.9 ± 0.031 | 92.83 ± 0.072 | >5.39 | >2.14 |
Ag4 | >500 | 84.62 ± 0.116 | 72.17 ± 0.036 | >6.93 | >5.91 |
Ag5 | 493.3 | 90.73 ± 0.236 | 78.79 ± 0.091 | 6.26 | 5.44 |
Ag6 | >500 | 305.2 ± 0.032 | 78.59 ± 0.605 | >6.36 | >1.64 |
Au1 | 19.94 | 77.38 ± 0.018 | 105.1 ± 3.139 | 0.19 | 0.26 |
Au2 | 295.6 | 143.2 ± 0.085 | 41.69 ± 0.210 | 7.09 | 2.06 |
Au3 | 28.77 | 194.9 ± 0.063 | 173.9 ± 0.087 | 0.17 | 0.15 |
Au4 | 31.98 | 277.6 ± 0.163 | 38.18 ± 0.158 | 0.84 | 0.12 |
Au5 | 58.59 | 284.0 ± 0.259 | 295.5 ± 0.259 | 0.198 | 0.21 |
Au6 | 77.52 | 5554 ± 1.371 | 62.54 ± 0.151 | 1.24 | 0.01 |
Glucantime | 1634 [74] | 176.3–191.7 | 113.2–130.2 | 14.43–12.55 | 9.26–8.52 |
3.6. Enzymatic Studies
3.7. Molecular Docking Studies
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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HL3FPh | HL5NO2Ph | HL6Al | Au1∙MeOH | Au2∙1.5MeOH | |
Formula | C14H14FN3O2S2 | C14H14N4O4S2 | C11H15N3O2S2 | C29H46AuClN6O5S4 | C30H38AuClN6O6S4 |
MM | 339.40 | 366.41 | 285.38 | 919.37 | 939.32 |
Crystal System | Triclinic | Triclinic | Triclinic | Monoclinic | Monoclinic |
Space Group | Pī | Pī | Pī | I2/m | I2/m |
a (Å) | 4.9348(3) | 4.9140(6) Å | 6.0952(2) | 12.636 | 12.412 |
b (Å) | 11.1075(8) | 11.2091(16) Å | 10.8751(5) | 21.517 | 20.741 |
c (Å) | 15.5724(12) | 16.178(2) Å | 11.5941(5) | 14.750 | 15.137 |
α (°) | 72.166(3) | 104.558(8)° | 99.638(2) | 90 | 90 |
β (°) | 81.679(3) | 97.154(7)° | 97.472(2) | 91.21 | 98.06 |
γ (°) | 84.997(3) | 93.675(7)° | 101.761(2) | 90 | 90 |
V (Å3) | 803.17(10) | 851.57(19) | 730.96(5) | 4009.5 | 3858.4 |
Z | 2 | 2 | 2 | 4 | 4 |
ρcalcd (g∙cm−3) | 1.403 | 1.429 | 1.297 | 1.523 | 1.617 |
μ (mm−1) | 0.351 | 0.339 | 0.362 | 3.985 | 4.145 |
Reflections Collected | 16,113 | 21,741 | 18,366 | 12,014 | 14,729 |
Independent reflections/Rint | 3333 [R(int) = 0.0610] | 3481 [R(int) = 0.1675] | 3000 [R(int) = 0.0532] | 5488 [R(int) = 0.1004] | 5324 [R(int) = 0.0880] |
Data/ restrict./ param. | 3333/0/200 | 3481/0/219 | 3000/0/164 | 5488/0/216 | 5324/15/289 |
Absorption Correction | Multi-scan | None | Multi-scan | Integration | Integration |
Max/min. Transmission | 0.7454 and 0.5304 | — | 0.7454 and 0.5412 | 0.7324 and 0.3793 | 0.7324 and 0.3793 |
R1 [I > 2σ(I)] | 0.0459 | 0.0598 | 0.0441 | 0.0416 | 0.0434 |
wR2 [I > 2σ(I)] | 0.1134 | 0.1257 | 0.1180 | 0.0723 | 0.0952 |
GOF | 1.042 | 1.002 | 1.108 | 0.686 | 0.878 |
CCDC Number | 2,341,449 | 2,341,450 | 2,341,451 | 2,341,452 | 2,341,453 |
HL3FPh | HL5NO2Ph | HL6Al | |
Bond lengths (Å) | |||
S(1)−O(1) | 1.4257(18) | 1.427(3) | 1.414(2) |
S(1)−O(2) | 1.4250(17) | 1.427(3) | 1.423(2) |
S(1)−N(1) | 1.650(2) | 1.661(3) | 1.654(2) |
S(1)−C(2) | 1.754(2) | 1.746(4) | 1.751(3) |
S(2)−C(1) | 1.667(2) | 1.653(4) | 1.692(2) |
N(1)−N(2) | 1.396(2) | 1.386(4) | 1.393(3) |
N(2) −C(1) | 1.359(3) | 1.362(5) | 1.353(3) |
N(3)−C(1) | 1.340(3) | 1.349(5) | 1.320(3) |
N(3)−C(9) | 1.421(3) | 1.410(4) | 1.454(3) |
Bond angles (°) | |||
O(1)−S(1)−O(2) | 120.19(12) | 119.80(17) | 121.77(16) |
O(1)−S(1)−N(1) | 104.29(11) | 104.58(17) | 106.58(13) |
O(2)−S(1)−N(1) | 105.94(11) | 105.54(16) | 102.74(14) |
O(1)−S(1)−C(2) | 108.49(11) | 108.68(17) | 108.19(15) |
O(2)−S(1)−C(2) | 108.17(12) | 108.14(18) | 109.18(13) |
N(1)−S(1)−C(2) | 109.35(11) | 109.77(17) | 107.48(11) |
N(2)−N(1)−S(1) | 116.70(16) | 117.4(3) | 116.64(17) |
C(1)−N(2)−N(1) | 121.05(19) | 122.0(3) | 119.84(17) |
C(1)−N(3)−C(9) | 127.74(19) | 128.6(3) | 125.3(2) |
Au1 | Au2 | |
---|---|---|
Bond lengths (Å) | ||
Au(1)−S(11) | 2.2961(12) | 2.2955(13) |
Au(1)−S(21) | 2.2962(12) | 2.2955(13) |
S(21)−C(21) | 1.723(5) | 1.703(5) |
S(11)−C(11) | 1.723(5) | 1.739(19) |
Bond angles (°) | ||
S(11)−Au(1)−S(21) | 176.73(13) | 175.16(9) |
C(21)−S(21)−Au(1) | 107.66(16) | 106.62(17) |
C(11)−S(11)−Au(1) | 107.66(16) | 107.3(7) |
AgI Complexes | Energy Gap (eV) | AuI Complexes | Energy Gap (eV) |
---|---|---|---|
Ag1 | 5.317 | Au1 | 5.077 |
Ag2 | 5.180 | Au2 | 4.802 |
Ag3 | 4.815 | Au3 | 5.028 |
Ag4 | 4.738 | Au4 | 4.810 |
Ag5 | 4.138 | Au5 | 3.956 |
Ag6 | 5.348 | Au6 | 5.102 |
Protein/Compound | Kd * (µmol L−1) | n ** | Kb ** × 104 (L mol−1) | Kd ** (µmol L−1) | Ksv *** × 104 |
---|---|---|---|---|---|
LbOYE/HL5NO2Ph | 35 ± 2 | 1.5 ± 0.1 | 5.2 ± 0.3 | 19 ± 1 | 6.5 ± 0.4 |
LbOYE/Au1 | 110 ± 30 | 1.8 ± 0.1 | 2.5 ± 0.2 | 39 ± 3 | 2.4 ± 0.2 |
LbOYE/Ag3 | 9.6 ± 0.7 | 2.0 ± 0.1 | 8.9 ± 0.2 | 11.2 ± 0.3 | 23 ± 2 |
Score | |||||
---|---|---|---|---|---|
Ligands | Ag Complexes | Au Complexes | |||
HL1Ch | 63.7 | [Ag(HL1Ch)2]NO3 | 95 | [Au(HL1Ch)2]Cl | 90 |
HL2Ph | 66.7 | [Ag(HL2Ph)2]NO3 | 88 | [Au(HL2Ph)2]Cl | 107 |
HL3FPh | 61.4 | [Ag(HL3FPh)2]NO3 | 102.7 | [Au(HL3FPh)2]Cl | 94 |
HL4ClPh | 63.3 | [Ag(HL4ClPh)2]NO3 | 95 | [Au(HL4ClPh)2]Cl | 98 |
HL5NO2Ph | 74.2 | [Ag(HL5NO2Ph)2]NO3 | 90 | [Au(HL5NO2Ph)2]Cl | 80 |
HL6Al | 61.1 | [Ag(HL6Al)2]NO3 | 79 | [Au(HL6Al)2]Cl | 79 |
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Borges, A.P.; Obata, M.M.S.; Libardi, S.H.; Trevisan, R.O.; Deflon, V.M.; Abram, U.; Ferreira, F.B.; Costa, L.A.S.; Patrocínio, A.O.T.; da Silva, M.V.; et al. Gold(I) and Silver(I) Complexes Containing Hybrid Sulfonamide/Thiourea Ligands as Potential Leishmanicidal Agents. Pharmaceutics 2024, 16, 452. https://doi.org/10.3390/pharmaceutics16040452
Borges AP, Obata MMS, Libardi SH, Trevisan RO, Deflon VM, Abram U, Ferreira FB, Costa LAS, Patrocínio AOT, da Silva MV, et al. Gold(I) and Silver(I) Complexes Containing Hybrid Sulfonamide/Thiourea Ligands as Potential Leishmanicidal Agents. Pharmaceutics. 2024; 16(4):452. https://doi.org/10.3390/pharmaceutics16040452
Chicago/Turabian StyleBorges, Alice P., Malu M. S. Obata, Silvia H. Libardi, Rafael O. Trevisan, Victor M. Deflon, Ulrich Abram, Francis B. Ferreira, Luiz Antônio S. Costa, Antonio O. T. Patrocínio, Marcos V. da Silva, and et al. 2024. "Gold(I) and Silver(I) Complexes Containing Hybrid Sulfonamide/Thiourea Ligands as Potential Leishmanicidal Agents" Pharmaceutics 16, no. 4: 452. https://doi.org/10.3390/pharmaceutics16040452
APA StyleBorges, A. P., Obata, M. M. S., Libardi, S. H., Trevisan, R. O., Deflon, V. M., Abram, U., Ferreira, F. B., Costa, L. A. S., Patrocínio, A. O. T., da Silva, M. V., Borges, J. C., & Maia, P. I. S. (2024). Gold(I) and Silver(I) Complexes Containing Hybrid Sulfonamide/Thiourea Ligands as Potential Leishmanicidal Agents. Pharmaceutics, 16(4), 452. https://doi.org/10.3390/pharmaceutics16040452