ANALYSIS OF THE MECHANISM ACTION OF JASMONATES USING COMPUTATIONAL CHEMISTRY APPROACHES

DOI: https://doi.org/10.29296/25877313-2018-04-05
Issue: 
4
Year: 
2018

G.F. Kurakin Student, Faculty of General Medicine, Tver State Medical University E-mail: phyzyk@mail.ru N.P. Lopina Ph.D. (Chem.), Department of Chemistry, Tver State Medical University G.E. Bordina Ph.D. (Biol.), Department of Chemistry, Tver State Medical University

literature, that this action is associated with similarity between jasmonates and prostaglandin J2 (PGJ2) derivatives, thus they can share common receptor – peroxysome proliferator activated receptor gamma (PPARγ). In this research a possible mechanism of antiinflammatory action of jasmonates was analysed using target prediction, docking and pharmacophore superimposition methods. Significant pharmacophoric similarity between jasmonates and prostaglandins has not been observed. Docking of jasmonates to homologymodelled prostanoid EP3 receptor displayed, that they probably do not act on this receptor. Jasmonates also have no pharmacophorically significant superimposition with PGJ2 and its derivatives in complex with PPARγ. It was concluded that chemical similarity between jasmonates and prostaglandins is not important for their action. In contrast with this result, significant pharmacophoric similarity to non-steroidal anti-inflammatory drugs (NSAIDs) was observed. It was found out that jasmonates can bind to PPARγ like NSAIDs, but not like prostaglandins. In addition to it, jasmonates can bind to PPARγ like indoleacetic acid derivatives, a novel class of endogenous ligands. Another finding is that jasmonates can superimpose to NSAID pharmacophore also in complex with cyclooxygenase (COX), so the posiibility of jasmonates to inhibit COX hypothesized.

Keywords: 
jasmonates
chemoinformatics
computational chemistry
mechanism of action
prostaglandins
NSAID
PPARγ

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