Key Laboratory of Tropical Medicinal Plant Chemistry of Hainan Province, College of Chemistry and Chemical Engineering, Hainan Normal University, Haikou 571127, China; Key Laboratory of Tropical Medicinal Resource Chemistry of Ministry of Education, Hainan Normal University, Haikou 571158, China; College of Chemistry, Chongqing Normal University, Chongqing 401331, China.
Key Laboratory of Tropical Medicinal Plant Chemistry of Hainan Province, College of Chemistry and Chemical Engineering, Hainan Normal University, Haikou 571127, China; Key Laboratory of Tropical Medicinal Resource Chemistry of Ministry of Education, Hainan Normal University, Haikou 571158, China.
Bioorg Chem. 2021 Apr;109:104701. doi: 10.1016/j.bioorg.2021.104701. Epub 2021 Feb 9.
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 IC values of 2.71 ± 0.18 and 2.68 ± 0.16 μM respectively. At the same time, the LDH release and LD 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.
设计、合成了四组双环共轭烯酮类化合物，通过对多穗柯因核心结构的改造，引入双环、双键和羰基等结构，以期抑制滑膜细胞的活性。对大鼠滑膜细胞进行体外实验，化合物 151 和 168 表现出较好的抑制活性，IC 值分别为 2.71 ± 0.18 和 2.68 ± 0.16 μM。同时，LDH 释放和 LD 试验结果表明，目标化合物具有低细胞毒性和急性毒性。通过口服给药对 CIA 模型进行体内试验，化合物 151 和 168 与阳性对照组甲氨蝶呤表现出相似的效果。
