Design Synthesis And Bioactivity Studies Of3-hydroxy1-4(1H)-pyridinone/-4(1H)-pyranone Derivatives

3-hydroxyl-4(lH)-pyridinone and3-hydroxyl-4(1H)-pyranone deri-vatives have shown various pharmacological effects such as antibacterial, antifugal, antimalarial, anti-inflammatory,treatment of Parkinson’s disease and antineoplastic. They produce these biology active maybe via different mechanisms. It is interesting that mimosine can inhibit eIF3a. EIF3a plays an important role in cell proliferation, growth and differ-rentiation. what is more, its expression is specifically high in lung cancer tissues and it is association with the sensitivity of lung cancer cells to the treatment of cisplatin. All of the above suggest that eIF3a probable be a potential target of lung cancer. Mimosine can also target prolyl4-hydroxylase inducing antifibrotic effects. Meanwhile, idiopathic pulmonary fibrosis and lung cancer have certain correlation.Treatment and prevention of lung cancer and fibrosis remain one of the most important problems. Herein, based on the structure of mimosine,3-hydroxyl-4(1H)-pyridinone and3-hydroxyl-4(1H)-pyranone deriva-tives were designed and synthesized. The structures of the49targe comp-ounds had been confirmed and the inhibitory activity been preliminary evaluated on A549and NIH3T3cells by MTT assay with Pt as positive control,1o has the best inhibitory activity to A549and NIH3T3cells. Shows the change of the structure of the influence of their active differences. Different structures Show different active.Anti-lung cancer and anti-fibrosis activity SAR analysis for reveal ed that:(1) series land3compounds have both strong activity. The activity of anti-fibrosis is better than anti-lung cancer of the other three serieses. So, their effect can be separated.(2)N substituents of3-hydroxyl-4(1H)-pyridinone derivatives variate from chain to cyclic chain. SAR analysis for revealed that cyclic chain, espe-cially aromatic is much better.(3) All of the serieses have their own regularity when their benzene ring are substituted by different groups at different place.This issue systematic synthesizes3-hydroxyl-4(1H)-pyridinone and3-hydroxyl-4(1H)-pyranone compounds. Their anti-lung cancer and anti-fibrosis activity have been evaluated and then the structure-activity relat-ionship has been described respectively. These achievements provide im-portant and basic information for the further studying and designing novel structures of better anti-cancer and/or anti-fibrosis activity.