Improved Antileishmanial Activity of Dppz through Complexation with Antimony(III) and Bismuth(III): Investigation of the Role of the Metal
Abstract
:1. Introduction
2. Results and Discussion
Compound | 1H-NMR data (ppm) | References | ||||
---|---|---|---|---|---|---|
Hc | Ha | Hd | He | Hb | ||
Dppz | 9.55 | 9.23 | 8.41 | 8.07 | 7.95 | Navarro et al. (2006) [26] |
Sb(dppz)Cl3 | 9.68 | 9.31 | 8.39 | 8.18 | 8.11 | This work |
Bi(dppz)Cl3 | 9.54 | 9.39 | 8.32 | 8.07 | 8.05 |
Sb(dppz)Cl3 | |
---|---|
Empirical formula | C19H10Cl3 N4O1.25Sb |
Formula weight | 542.41 |
Temperature (K) | 293(2) |
Crystal system | Monoclinic |
Space group | P2(1)/c |
a (Å) | 10.3244(2) |
b (Å) | 13.2760(3) |
c (Å) | 14.5753(3) |
α (o) | 90 |
β (o) | 92.0930(19) |
γ (o) | 90 |
V (Å3) | 1994.44(7) |
Z | 4 |
F (000) | 1056 |
Dcalc (mg/m3) | 1.805 |
Crystal dimensions mm3 | 0.2 × 0.2 × 0.3 |
θ Range (o) | 4.29-62.65 |
Reflections collected | 9035 |
Independent reflection | 3138 |
Rint | 0.0355 |
Maximum/minimum transmission | 1.000 / 0.30303 |
Data/restraints/parameters | 3138 / 0 / 247 |
Goodness-of-fit on F2 | 1.060 |
Final R indices | R1 = 0.0352, wR2 = 0.0826 |
[I > 2σ(I)] | 2478 |
R indices (all data) | R1 = 0.0522, wR2 = 0.0886 |
Largest difference in peak/hole (e·A−3) | 0.761 and −0.560 |
Sb-N(2) | 2.245(4) | N(2)-Sb-N(1) | 71.44(14) |
Sb-N(1) | 2.345(4) | N(1)-Sb-Cl(3) | 159.07(10) |
Sb-Cl(3) | 2.4992(15) | N(2)-Sb-Cl(3) | 87.73(11) |
Sb-Cl(1) | 2.5126(13) | N(2)-Sb-Cl(1) | 82.14(10) |
Sb-Cl(2) | 2.6348(14) | N(1)-Sb-Cl(1) | 84.23(10) |
N(1)-C(16) | 1.334(6) | Cl(3)-Sb-Cl(1) | 95.22(5) |
N(1)-C(12) | 1.351(6) | N(2)-Sb-Cl(2) | 80.25(10) |
N(2)-C(22) | 1.336(6) | N(1)-Sb-Cl(2) | 82.97(10) |
N(2)-C(26) | 1.368(6) | Cl(3)-Sb-Cl(2) | 91.68(5) |
Cl(1)-Sb-Cl(2) | 160.80(5) |
Strain | IC50 (μM) ± SEM (CI 95%) | |||||
---|---|---|---|---|---|---|
Dppz | dppzBiCl3 | dppzSbCl3 | TA * | SbCl3 | BiCl3 | |
L. infantum chagasi (WT) | 0.81 ± 0.04 | 0.59 ± 0.01 | 0.62 ± 0.01 | 100 ± 3 | 341 ± 2 | 563 ± 2 |
(0.71–0.9) | (0.56–0.63) | (0.59–0.65) | ||||
L. infantum chagasi (SbR) | 1.86 ± 0.08 | 0.61 ± 0.02 | 0.57 ± 0.01 | >2,700 | 462 ± 3 | >500 |
(1.69–2.03) | (0.56–0.66) | (0.55–0.60) | ||||
L. amazonensis (WT) | >2 | 1.07 ± 0.03 | 0.95 ± 0.02 | 83 ± 1 | 362 ± 2 | 621 ± 2 |
(1.01–1.14) | (0.89–1.01) | |||||
L. amazonensis (SbR) | 2.00 ± 0.05 | 1.12 ± 0.01 | 0.92 ± 0.02 | >2,700 | 1503 ± 2 | >500 |
(1.89–2.10) | (1.08–1.16) | (0.86-0.97) |
Dppz | [Bi(dppz)Cl3] | [Sb(dppz)Cl3] | |
---|---|---|---|
CC50 (μM) * | 12.5 | 4.8 | 7.0 |
SI # | 15.4 | 8.1 | 11.3 |
3. Experimental
3.1. General
3.2. Synthesis of the Complexes [Sb(dppz)Cl3] and [Bi(dppz)Cl3]
3.2.1. Synthesis of [Sb(dppz)Cl3] (1)
3.2.2. Synthesis of [Bi(dppz)Cl3] (2)
3.2.3. Stability of the Complexes
3.3. X-ray Crystallography
3.4. Antileishmanial and Cytotoxic Activities
3.4.1. Parasite Culture
3.4.2. Antileishmanial Activity Assay
3.4.3. Cytotoxicity Assay against Peritoneal Macrophages
3.5. Statistical Analysis
3.6. n-Octanol/Water Partition Coefficient
4. Conclusions
Acknowledgments
References
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Lizarazo-Jaimes, E.H.; Monte-Neto, R.L.; Reis, P.G.; Fernandes, N.G.; Speziali, N.L.; Melo, M.N.; Frézard, F.; Demicheli, C. Improved Antileishmanial Activity of Dppz through Complexation with Antimony(III) and Bismuth(III): Investigation of the Role of the Metal. Molecules 2012, 17, 12622-12635. https://doi.org/10.3390/molecules171112622
Lizarazo-Jaimes EH, Monte-Neto RL, Reis PG, Fernandes NG, Speziali NL, Melo MN, Frézard F, Demicheli C. Improved Antileishmanial Activity of Dppz through Complexation with Antimony(III) and Bismuth(III): Investigation of the Role of the Metal. Molecules. 2012; 17(11):12622-12635. https://doi.org/10.3390/molecules171112622
Chicago/Turabian StyleLizarazo-Jaimes, Edgar H., Rubens L. Monte-Neto, Priscila G. Reis, Nelson G. Fernandes, Nivaldo L. Speziali, Maria N. Melo, Frédéric Frézard, and Cynthia Demicheli. 2012. "Improved Antileishmanial Activity of Dppz through Complexation with Antimony(III) and Bismuth(III): Investigation of the Role of the Metal" Molecules 17, no. 11: 12622-12635. https://doi.org/10.3390/molecules171112622