Design, synthesis and anti-rheumatoid arthritis evaluation of double-ring conjugated enones

[Display omitted] •Four series of double-ring conjugated enones were designed and synthesized for inhibit synovial cell activity.•All compounds were in vitro evaluated for their rats synovial cells inhibitory activity.•Compound 151 and 168 showed a good inhibitory activities, with IC50 values of 2.71 ± 0.18 and 2.68 ± 0.16 μM.•Compounds 151 and 168 were exhibited similar efficacy to positive control group methotrexate in vivo.•The LDH release and LD50 test results showed that the target compounds was low cytotoxicity and low acute toxicity. Four series of double-ring conjugated enones were designed, synthesized and studied for the inhibition of synovial cell activity through the modification of Dysodensiol K core structure, double-ring, double-bond and double-carbonyl groups. For in vitro synovial cell assay of rats, compound 151 and 168 exhibited good inhibitory activities, with IC50 values of 2.71 ± 0.18 and 2.68 ± 0.16 μM respectively. At the same time, the LDH release and LD50 test results revealed that the target compounds were low cytotoxicity and acute toxicity. For in vivo CIA model test through the oral administration, compounds 151 and 168 were exhibited similar effect to positive control group methotrexate.