Papers of the Week

Compound (4-(3,5-di-tert-butyl-4-hydroxybenzylamine)benzenesulfonamide) (LQFM275) was designed and synthesized from darbufelone and sulfanilamide as a new multi-target for the treatment of inflammatory diseases. LQFM275 showed a great range of safe cytotoxicity profile (100-400 μM) evaluated by MTT assay, preventing damage induced by lipopolysaccharide (LPS) in EA.hy926 cell line. In mice, the acute oral treatment with LQFM275 (57, 114, and 228 mg/kg) reduced the number of writhing by 26, 37, and 49 %, respectively. LQFM275 (114 mg/kg) also presented an antinociceptive effect, reducing by 57 % the nociceptive response in the second phase of the formalin test and by 47 % the Carrageenan(Carra)-induced hyperalgesia. That effect was dependent on its anti-inflammatory activity. LQFM275 (114 mg/kg) also reduced 42 % and 31 % of the Carra and LPS-induced edema, respectively. The pleurisy test attenuated the leukocyte migration induced by Carra and LPS by reducing the number of polymorphonuclear cells (by 39 and 36 %, respectively). The production of reactive oxygen species in the pleural exudate was reduced, which is shown by a decrease in myeloperoxidase (MPO) activity (Carra = 35 % and LPS = 40 %) and in levels of pro-inflammatory cytokines TNF-α and IL-1β (Carra = 48 % and LPS = 47 e 36 %). On the other hand, it increased the levels of anti-inflammatory cytokines, IL-4, and IL-10 (Carra = 50 % and LPS = 21 and 53 %). Moreover, LQFM275 demonstrated to be a dual COX-2 and 5-LOX inhibitor (IC = 81 and 167 μM, respectively). Therefore, the promising anti-inflammatory and antinociceptive effects of LQFM275 provide an opportunity for a new multi-target drug development.