Albany 2015:Book of Abstracts
June 9-13 2015
©Adenine Press (2012)
Antiinflamatory Activity of Phenolic Compounds Extracted from Uruguayan Propolis and Grape
Propolis and grape pomace have significant amounts of phenols that can take part in antiinflammatory mechanisms (Zunini et al., 2010).
As the cyclooxygenases 2 and 1 (COX-2 and COX-1) are involved in them, the ability of phenolic extracts to inhibit these enzymes was analyzed in vitroand in silico. Samples of propolis and grape pomace from 2 grape species collected between 2008 and 2013 from different places of Uruguay and in different seasons were used (Wang etal., 2010); Rimon et al, 2010)
Based on phenols previously identified, and taking as reference a crystallographic structure of COX-2 (3LN1) and COX-1 (3KK6) bound to celecoxib, a molecular docking procedure was adjusted to reproduce the celecoxib position in the cristal and then used with the phenolic molecular models. The docking was performed with the MOE 2009.10 (Molecular Operating Environment) (ChemComp Co.) with the Affinity dG function for Scoring and Re-scoring, the MMFF94x force field to refinement and the Alpha Triangle as the placement algorithm.
When phenols were docked to COX-2, the most common binding aminoacids were Tyr341, Tyr101, Val74, Pro71, Arg106, Glu510, Leu109 and Ser105. In the case of COX-1, they were Glu524, Pro86 and Arg120. From best docked phenol-COXs complexes, 10 ns of Molecular Dynamics simulations were performed by triplicate, using Amber99 force field. The interaction energy phenol-environment was averaged and compared with the docking binding energies (Score) for COX-2 and COX-1 respectively and with those of in vitroassays that showed an inhibition range of 5,0 - 43,5 % of COX-2 and 6,1 - 46,0 % of COX-1.
Acknowledgments: PEDECIBA QUIMICA for the economic support, and Urimpex and Castel Pujol for the propolis and grape pomace samples respectively.
J. L Wang, D. Limburg, M.J. Graneto, J. Springer, J.R. Hamper, S. Liao, J.L. Pawlitz,R.G. Kurumbail, T. Maziasz, J.J Talley, J.R. Kiefer, J. Carter. The novel benzopyran class of selective cyclooxygenase-2 inhibitors. Part 2: the second clinical candidate having a shorter and favorable human half-life (2010). Bioorganic and Medicinal Chemistry Letters 20, 7159-7163.
G. Rimon, R.S. Sidhu, D.A. Lauver, J.Y. Lee, N.P Sharma, C. Yuan, R.A. Frieler, R.C. Trievel, B.R. Lucchesi, W.L. Smith. (2010). Coxibs interfere with the action of aspirin by binding tightly to one monomer of cyclooxygenase-1. Proceedings of the National Academy of Sciences, 107, 28-33.
Elena Alvareda 1, 2
1Centro de Bioinformática Estructural