Design and synthesis of novel aza-ursolic acid derivatives: in vitro cytotoxicity and nitric oxide release inhibitory activity

Aim: Inducible nitric oxide synthase (iNOS) is a validated target for anti-inflammatory treatment. Based on the authors' previous work, novel aza-ursolic acid derivatives were designed and synthesized and their inhibitory activities against lipopolysaccharide (LPS)-induced nitric oxide (NO) release from RAW264.7 cells was evaluated. Materials & results: Sixteen novel derivatives were screened for their in vitro inhibitory activity against NO release using Griess assays and the cytotoxicity was evaluated using MTT assays. The presence of furoxan joined to the A-ring of ursolic acid and N-methylpiperazine groups in the lead compound was identified for anti-inflammatory activity, and compound 21b showed 94.96% inhibition of NO release at 100 mu M with an IC50 value of 8.58 mu M. Conclusion: Compound 21b has potential anti-inflammatory activity with low cytotoxicity that warrants further preclinical study and evaluation.