Análise dos compostos majoritários do óleo essencial das folhas de aroeira (Schinus terebinthifolius Raddi) para o tratamento da tendinite: identificação fitoquímica e um estudo in silico

Abstract

Tendonitis is an inflammatory process that occurs in a tendon, the inflammatory process is a protective response of the body, various chemical substances increase the production of prostanglandins synthesized by the enzymes Cyclooxygenases 1 and 2, anti-inflammatory drugs act by inhibiting these enzymes. In the search for new drugs to treat the most diverse types of illnesses, the use of medicinal plants has a tradition in popular medicine throughout the world, and we used Schinus terebinthifolius Raddi, as it is widely used for this purpose. In this work, we extracted the essential oil (EO) from the leaves of a sample of this plant by hydrodistillation using a Clevenger-type apparatus modified by Gottlieb, and then identified its components using the Gas Chromatography and Mass Spectrometry (GC-MS) technique, where 95 different compounds were identified, from which the 10 majority compounds were chosen for ADMET and Molecular Anchoring (MA) studies. In the ADMET evaluation, all showed good results for further studies. In the molecular docking, the best fit between the protein (receptor) and the ligand was analyzed. The proteins chosen were COX-1 (Protein Data Bank No. 3N8X, crystallographic ligand nimesulide) and COX-2 (Protein Data Bank No. 5KIR, crystallographic ligand rofecoxib), which have a direct action in the formation of the inflammatory process. For this analysis, the programs Chimera1.16 were used to prepare the molecules and Autodock Vina1.2. 3 for AM, the compounds analyzed were myrcene, cadinene, humulene, copaene, limonene, caryophyllene oxide, perilen, canophrene, murolene and 1,1,3a-Trimethyl-7-methylenedecahydro-1Hcyclopropa[a]naphthalene, and the anti-inflammatory diclofenac for comparison. After redocking the crystallographic ligands, the docking was carried out and we obtained binding energy values in Autodock Vina (AGbind kcal/mol) of -8.781 for murolene with Cox1 and camphorene with -9.356 as the highest values for Cox2. It was observed that caryophyllene oxide showed the most different values between the Cox isoforms, being more inhibitory to Cox2. The LigPLot program was used to analyze the interactions between the ligands and the protein's active site. Most of the hydrophobic interactions were observed, with only one hydrogen bond-type interaction in the Cox1-nimesulide, Cox1-diclofenac, Cox1-rofecoxib complex, and the Cox2-nimesulide, Cox2- diclofenac, Cox2-rofecoxib complex, thus explaining its lower free energy value and greater interaction. It can be concluded from the partial analysis of this EO that the compounds mentioned present a possible positive response for anti-inflammatory action, especially caryophyllene oxide because it is more inhibitory to Cox2 than to 1 and thus possibly has less unwanted effects.