Identification of new superwarfarin-type rodenticides by structural similarity. The docking of ligands on the vitamin K epoxide reductase enzyme’s active site

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The rodenticide brodifacoum is highly toxic to mammals and birds, and extremely toxic to fish. It is a highly cumulative poison due to its high lipophilicity and extremely slow elimination. For this reason, it may be interesting to find similar compounds in order to enlarge the spectrum of vitamin K epoxide reductase enzyme inhibitors used today in pest control. We used the Similar Compounds search type of the Chemical Structure Search of the PubChem Compound Database to locate records that are similar to the chemical structure of brodifacoum, using pre-specified similarity thresholds. Using the threshold ≥ than 95% for the similar structures criteria, we found 14 compounds (from over 30 million entries) that meet this criteria. Two of these compounds have a better binding affinity to vitamin K epoxide reductase enzyme than brodifacoum, but the binding energy of the other 12 substances is also high, having identical or lower lipophilicity; consequently, they will eliminate faster, possibly lacking a part of the adverse effects.

[1] American Bird Conservancy. Retrieved: 9 April 2015.

[2] Retrieved: 19 April 2015.

[3] U.S. National Library of Medicine, TOXNET®: Toxicology Data Network. Retrieved: 9 April 2015.

[4] Morris, G. M., Huey, R., Lindstrom, W., Sanner, M. F., Belew, R. K., Goodsell, D. S., Olson, A. J. (2009), Autodock4 and AutoDockTools4: automated docking with selective receptor flexibility. Journal of Computational Chemistry 16, 2785–2791.

[5] Trott, O., Olson, A. J. (2010), AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization and multithreading. Journal of Computational Chemistry 31, 455–461.

[6] O’Boyle Noel, M., Banck, M., James Craig, A., Morley, C., Vandermeersch, T., Hutchison Geoffrey, R. (2011), Open Babel: An open chemical toolbox. J. Cheminf. 3, 33–47.

[7] National Center for Biotechnology Information. PubChem Compound Database; CID=54680676, (accessed: Dec. 27, 2013 and Apr. 12, 2015).

[8] Sanner, M. F. (1999), Python: A programming language for software integration and development. J. Mol. Graphics Mod. 17, 57–61.

[9] Sanner, M. F., Spehner, J.-C., Olson, A. J. (1996), Reduced surface: an efficient way to compute molecular surfaces, Biopolymers 38(3), 305–320.

[10] Bajaj, C., Park, S., Thane, A. (2002), A parallel multi-PC volume rendering system. ICES and CS Technical Report, University of Texas.

[11] Bajaj, C., Pascucci, V., Schikore, D. (1996), Fast isocontouring for improved interactivity. In: Proceedings of ACM Siggraph/IEEE Symposium on Volume Visualization, ACM Press, San Francisco, CA, 39–46.

[12] Sanner, M. F., Stoffler, D., and Olson, A. J. (2002), ViPEr a visual programming environment for Python. In: 10th International Python Conference, Virginia.

[13] Li, W., Schulman, S., Dutton, R. J., Boyd, D., Beckwith, J., Rapoport, T. A. (2010), Structure of a bacterial homologue of vitamin K epoxide reductase. Nature 463, 507–512.

[14] Bursulaya, B. D., Totrov, M., Abagyan, R., Brooks, C. L. (2003), Comparative study of several algorithms for flexible ligand docking., J. Comput. Aided Mol. Des. 17(11), 755–763.

[15] Wolf, L. K. (2009), New software and websites for the chemical enterprise. Chemical & Engineering News 87, 31.

Acta Universitatis Sapientiae, Agriculture and Environment

The Journal of "Sapientia" Hungarian University of Transylvania

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