A series of indole-derived γ-hydroxy propiolate esters as potent anti-inflammatory agents: Design, synthesis, in-vitro and in-vivo biological studies

A variety of novel indole-derived γ-hydroxy propiolate esters were designed, synthesized, and evaluated for their anti-inflammatory activity in-vitro and in-vivo. According to the nitric oxide (NO) inhibitory analysis, all compounds showed potent NO inhibitory ability in a dose-dependent manner, with no apparent cytotoxicity. The model compound, L-37, also exhibited significant potency in PGE₂ inhibition. In addition, compounds L-37 and L-39 can downregulate the expression of COX-2 Enzyme at 5 μM via ELISA experiment. Compound L-37 (1 μM) also inhibited the PGF₁ production as well as the expression of COX-1, but displayed weak inhibition activity towards the Leukotrienes (LT) and Thromboxane-B2 (TXB-2) production. However, the expression of 5-LOX was significantly inhibited by compound L-39 at 5 μM. Xylene-induced ear edema model was explored for in-vivo anti-inflammatory evaluation, compound L-37 showed similar inhibitory activity compared with celecoxib, approximately 80% at 50 mg/kg dosage. Every outcome showed that the newly synthesized compounds can effectively inhibit inflammation.

Anti-inflammatory; Celecoxib; Leukotriene; Nitric oxide; γ-hydroxy propiolate esters.