Rutin is a flavonoid widely distributed in the plant kingdom and has presented several pharmacological effects, such as anti-inflammatory, antihypertensive, antioxidant, antifungal, antiallergic and anti-tumor1,2. However, despite the already observed results, the efficacy of this compound can be significantly limited by its low solubility and stability in lipophilic medium3. The development of lipophilic derivatives of rutin by esterification of some hydroxyl groups with fatty acid chains may be an efficient strategy to change their physicochemical properties and bioactivity4. This work aims to produce rutin esters by reactions catalyzed by immobilized lipase from C. antarctica (Novozym 435) with the purpose of producing bioactive derivatives. The reactions were conducted in the ratio of 1 (Rutin): 5 (C4-C18 fatty acids) in 2-methylbutan-2-ol in the presence of 3 Å molecular sieve. All reactants were previously dried at desiccator for 7 days. The solvent was previously dried for 5 days with 3 Å molecular sieves (100 g/L). To initiate the esterification reaction, 15% (p/p) de immobilized lipase from C. antarctica (Novozym 435) was added to the reaction mixture. The reactions were conducted on the shaker at temperature of 55 °C, rotation of 200 rpm and time of 24 to 96 hours. Control experiments were did without enzyme.3,5. The extent of the reaction was monitored by TLC normal phase (F254 -Sorbent®) and HPLC (Shimadzu LC-20AT/ Kinetex 2,6µ biphenyl 100 x 4,6 mm column) analysis. The reaction was terminated by removing the enzyme and molecular sieves by filtration. Samples were analyzed using a HPLC system (Thermo Fisher Scientific, Germany) equipped with a UV detector (254 and 355 nm) coupled to a mass spectrometer with electron spray ionization source (LCQ, Thermo Fisher Scientific, USA). MS parameters were tuned as follows: electrospray negative ionization mode, capillary temperature of 275 °C and source voltage at 5.50 kV. From these analyzes it was possible to verify the esterification of the rutin with different chains of fatty acids, being observed the following m/z 665, 679, 735, 791, 819, 847, 875, 873 and 871 which demonstrate the esterification of the rutin with propionic, butyric, caprylic, lauric, myristic, palmitic, stearic, oleic and linoleic acids, respectively. In this way, the production of these compounds can be considered a strategy to obtain bioactive derivatives that present a greater activity, stability and bioavailability than the original molecule. As perspectives for this work we have the structural elucidation of these compounds to verify the position of the esterification and evaluation of the antitumor potentials of the substrates and reactional products.

References
1 GULLON et al. Trends in Food Science & Technology. v. 67, p. 220-235, 2017
2GANESHPURK and SALUJA. Saudi Pharmaceutical Journal, v.25, n.2, 2016.
3MELLOU et al. Journal of biotechnology., v. 116, p. 295-304, 2005.
4SALEM et al. Process Biochemistry, v.45, n.3, p. 382–389, 2010.
5VISKUPICOVA et al. Food Chemistry, v. 123, p. 45-50, 2010.