New analogs of LASSBio‐1829Cl with anti‐inflammatory properties

Abstract

IntroductionInflammation is a benefice response of the immune system in response to an infectious agent or tissue damage. During the inflammatory process, there are vascular and cellular involvement. Most common drugs indicated are the non‐steroidal anti‐inflammatory drugs (NSAID). However, due to the diversity of their side effects the continue search for new substances is still a goal for researchers. In this respect LASSBio‐1829Cl was firstly described with significant anti‐inflammatory property. In view of this activity the new analogues, LASSBio‐2060 and LASSBio‐2061, were synthetized. So, the aim of the present work was to evaluate the anti‐inflammatory effects of LASSBio‐2060 and LASSBio‐2061 using traditional methods of inflammation.MethodsMale Swiss Webster mice (28–32g, n=6) were used in models of formalin‐induced licking or carrageenan‐induced cell migration into the subcutaneous air pouch (SAP) models. Mice were orally treated with LASSBio‐2060 or LASSBio‐2061 (10, 30 or 100 μmol/kg). After 1 hour mice received intraplantar injection of formalin (2.5%, 50 μL) and the time that mice spent licking the formalin‐injected paw was recorded with a chronometer. In SAP model, after oral administration of substances, mice received carrageenan (1%, 1 mL) or saline injection into SAP and 24 hours later mice are euthanized and exudate collected for further measurements. Results are presented as media ± sd. Statistical analysis were performed by ANOVA followed by Bonferroni test (*p<0.05). The protocol for use of animals was approved by CEUA/UFRJ and received the number DFBCICB015‐04/16.ResultsAlthough none of the substance inhibited the 1st phase of formalin‐induced licking both had an effect in 2nd phase as shown: vehicle‐treated group: 161.4±67.1sec; LASSBio‐2060, 30μmol/Kg: 173.2±9.6sec; 100μmol/kg: 92.3±37.2*sec. LASSBio‐2061 10μmol/kg: 128.2±50.8sec; 30μmol/kg: 34.0±10.6*sec; 100μmol/kg: 80.3±43.6*sec. LASSBio‐2060 inhibited leukocyte migration in a dose‐dependent manner. vehicle‐treated group: 96.2±31.6 ×103 cells/μL; 10μmol/kg: 62.3±14.2* ×103 cells/μL; 30μmol/kg: 43.7±17.0* ×103 cells/μL; 100μmol/kg: 31.5±12.0* ×103 cells/μL.. LASSBio‐2061 also inhibited leukocyte migration into the SAP at higher doses: vehicle‐treated group: 79.3±28.9 ×103 cells/μL; 10μmol/kg: 72.5±35×103 cells/μL; 30μmol/kg: 30.2±12.7*×103 cells/μL; 100μmol/kg: 48.4±7.6*×103 cells/μL. Both compounds reduce production of the cytokine IL‐1β. LASSBio‐2060, vehicle‐treated group: 2.356.3±783.4 pg/mL; 30μmol/kg: 1.246.3±411.9* pg/mL; 100μmol/kg: 1.359.5±534.0* pg/mL. LASSBio‐2061, significantly reduced only at its lower dose, vehicle‐treated group: 1.813.66 ± 553.7 pg/mL; 10μmol/kg: 1.024.7± 237.5 pg/mL.ConclusionThe results suggest that both substances reduced cell migration induced by carrageenan and reduced the production of cytokine IL‐1β indicating them as promising anti‐inflammatory.Support or Funding InformationFinancial support: CAPES, CNPq, FAPERJ Institute Vital Brazil (donation of mice) Technical Support: Alan MinhoThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.