Discovery of novel limonin derivatives as potent anti-inflammatory and analgesic agents

Novel series of limonin derivatives ( Ⅴ-A-1 - Ⅴ-A-8 , Ⅴ-B-1 - Ⅴ-B-8 ) were synthesized by adding various tertiary amines onto the C (7)-position of limonin. The synthesized compounds possessed favorable physicochemical property, and the intrinsic solubility of the novel compounds were significantly improved, compared with limonin. Different pharmacological models were used to evaluate the analgesic and anti-inflammatory activities of the target compounds. Compound Ⅴ-A-8 exhibited the strongest in vivo activity among the novel limonin analogs; its analgesic activity was more potent than aspirin and its anti-inflammatory activity was stronger than naproxen under our testing conditions.