Pharmacological appraisal of ligustrazine based cyclohexanone analogs as inhibitors of inflammatory markers

The targeting of pro-inflammatory enzymes becomes a therapeutic intervention when acute inflammation is proliferating in pathological conditions. This research is intended to carry out an evaluation of inhibiting and inducing enzymes with inflammatory associations with 28 cyclohexanone analogs based on the ligustrazine. Tests were undertaken with inhibitor screening assay kits using a range of synthetic compounds to investigate how they could inhibit the activity of cyclooxygenase (COX) enzymes, secretory phospholipase A₂ (sPLA₂), and lipoxygenase (LOX) enzyme. Significant and similar inhibitory activities against sPLA₂ with were noted with synthetic compounds which included 1f and 1g (IC₅₀ = 2.2 μM). The optimal inhibitory activity regarding LOX enzyme was shown with compounds 1d (IC₅₀ = 8.1 μM) and 1e (IC₅₀ = 7.5 μM). Additionally, the compounds 1b, 1d, 1e, 2n, and 2o were shown to be significant inhibitors of COX-1 activity with IC₅₀ values 0.09 to 0.7 μM. The outcomes of assays for COX inhibition demonstrated that the same compounds had a further strong inhibitive influence on the COX-2 enzyme, and certain compounds such as 1d, 1e, and 2n demonstrated enhanced potency compared with positive controls.