Structure-Based Virtual Screening and In Vitro Evaluation of New Trypanosoma cruzi Cruzain Inhibitors
Abstract
1. Introduction
2. Results and Discussion
2.1. Virtual Screening
2.2. In Vitro Evaluation
2.3. Enzyme Inhibition
3. Materials and Methods
3.1. Structure-Based Virtual Screening
3.2. In Vitro Evaluation
3.3. Enzyme Inhibition
4. Conclusions
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
Abbreviations
Nfx | Nifurtimox |
Bzn | Benznidazole |
Cz | Cruzain |
CD | Chagas disease |
IC50 | Inhibitory concentration |
LC50 | Lytic concentration |
References
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Compound | Structure | Binding Energy (kcal/mol) | Activity Reported |
---|---|---|---|
Z1 ZINC129684040 | −8.6 | None | |
Z2 ZINC9873043 | −8.3 | Inhibitor of cannabinoid receptor type 2 | |
Z3 ZINC9870651 | −8.2 | None | |
Z4 ZINC9835465 | −8.2 | Amine oxidase inhibitor | |
Z5 ZINC9715287 | −8.1 | Amine oxidase inhibitor | |
Z6 ZINC9861447 | −8.1 | Amine oxidase inhibitor | |
Z7 ZINC9873693 | −8.1 | Inhibitor of aldo keto reductases | |
Z8 ZINC14741665 | −8.0 | Inhibitor of cathepsin S | |
Z9 ZINC60293658 | −8.0 | None | |
Z10 ZINC9867137 | −8.0 | Amine oxidase inhibitor | |
186 | −6.6 | Cz inhibitor |
Compound | Epimastigotes | Bloodstream Trypomastigotes | |
---|---|---|---|
LC50 (µM) T. cruzi INC-5 | LC50 (µM) | ||
T. cruzi NINOA | T. cruzi INC-5 | ||
Z2 | 239.40 ± 9.3 | >250 | >250 |
Z3 | >250 | >250 | >250 |
Z5 | 36.26 ± 9.9 | 166.21 ± 14.5 | 185.1 ± 8.5 |
Z6 | >250 | >250 | >250 |
S1 | >250 | >250 | >250 |
Nfx | 38.36 ± 5.2 | 99.41± 11.1 | 117.16 ± 16.36 |
Bnz | 9.64 ± 4.2 | 183.1 ± 16.2 | 225.40 ± 26.5 |
Compound | IC50 (µM) |
---|---|
Z2 | 1410.05 |
Z3 | 84.37 |
Z5 | 56.23 |
Z6 | 50.35 |
SI | >200 |
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Herrera-Mayorga, V.; Lara-Ramírez, E.E.; Chacón-Vargas, K.F.; Aguirre-Alvarado, C.; Rodríguez-Páez, L.; Alcántara-Farfán, V.; Cordero-Martínez, J.; Nogueda-Torres, B.; Reyes-Espinosa, F.; Bocanegra-García, V.; et al. Structure-Based Virtual Screening and In Vitro Evaluation of New Trypanosoma cruzi Cruzain Inhibitors. Int. J. Mol. Sci. 2019, 20, 1742. https://doi.org/10.3390/ijms20071742
Herrera-Mayorga V, Lara-Ramírez EE, Chacón-Vargas KF, Aguirre-Alvarado C, Rodríguez-Páez L, Alcántara-Farfán V, Cordero-Martínez J, Nogueda-Torres B, Reyes-Espinosa F, Bocanegra-García V, et al. Structure-Based Virtual Screening and In Vitro Evaluation of New Trypanosoma cruzi Cruzain Inhibitors. International Journal of Molecular Sciences. 2019; 20(7):1742. https://doi.org/10.3390/ijms20071742
Chicago/Turabian StyleHerrera-Mayorga, Verónica, Edgar E. Lara-Ramírez, Karla F. Chacón-Vargas, Charmina Aguirre-Alvarado, Lorena Rodríguez-Páez, Verónica Alcántara-Farfán, Joaquín Cordero-Martínez, Benjamín Nogueda-Torres, Francisco Reyes-Espinosa, Virgilio Bocanegra-García, and et al. 2019. "Structure-Based Virtual Screening and In Vitro Evaluation of New Trypanosoma cruzi Cruzain Inhibitors" International Journal of Molecular Sciences 20, no. 7: 1742. https://doi.org/10.3390/ijms20071742
APA StyleHerrera-Mayorga, V., Lara-Ramírez, E. E., Chacón-Vargas, K. F., Aguirre-Alvarado, C., Rodríguez-Páez, L., Alcántara-Farfán, V., Cordero-Martínez, J., Nogueda-Torres, B., Reyes-Espinosa, F., Bocanegra-García, V., & Rivera, G. (2019). Structure-Based Virtual Screening and In Vitro Evaluation of New Trypanosoma cruzi Cruzain Inhibitors. International Journal of Molecular Sciences, 20(7), 1742. https://doi.org/10.3390/ijms20071742