Structural Modification And Anti-IPF Activity Of Matrine Derivatives

Idiopathic pulmonary fibrosis is an irreversible,interstitial pneumonia that is confined to the lungs and progressive fibrosis.Its pathogenesis and mechanism are unknown and are limited to adults.In recent years,with the development of society,the incidence of idiopathic pulmonary fibrosis is increasing year by year,which poses a great threat to our health.Therefore,we explore the mechanism of idiopathic pulmonary fibrosis and study the efficiency.The drug has become our top priority.Sophora flavescens contains a variety of alkaloids,such as matrine,sophoridine,sophoridine,guanamine,oxygen,and saponin.These alkaloids have a wide range of pharmacological activities,such as anti-liver fibrosis,anti-inflammatory,anti-viral,immune regulation and the like.At the same time,some small aromatic molecules of natural fatty acids naturally exist in Chinese herbal medicines,and their structure contains an acryl ring-substituted benzene ring.Such small molecules also have anti-inflammatory,anti-fibrotic and other activities,such as cinnamaldehyde and cinnamic acid in cinnamon,ferulic acid contained in Chuanxiong,and the like.Therefore,this project decided to structurally modify matrine,sophoridine and sophoridine,and introduce active fragments of cinnamic acid and its analogues into their side chains,hoping to improve the pharmacological activities of both,and obtain more activity.Good and less toxic new matrine derivatives have laid a foundation for the future structural modification of matrine derivatives and the study of anti-idiopathic pulmonary fibrosis.Our group uses matrine,sophoridine and sophoridine as starting materials to replace Cinnamon by a series of reactions such as oxidative ring opening reaction,alkylation reaction,reduction reaction,condensation reaction,hydrolysis reaction and salt formation reaction.The acyl structure was introduced into the three types of matrine,sophoridine and sophoridine.A novel matrine derivative was synthesized by the idea of splicing,and it is hoped that its pharmacological activity can be improved to obtain anti-idiopathic pulmonary fibrosis.A target compound with good activity.A total of 34 matrine derivatives were synthesized in this paper,which were 5a-51 with matrine as the starting material,10a-10k with saponin as the starting material and saponin as the starting material.15a-15k.The structures of all the synthesized compounds were confirmed by 1H-NMR,13C-NMR and HRMS characterization.In this paper,the anti-proliferative effect of synthetic target compounds on fibrotic cells(NIH3T3)was investigated by MTT assay.The pharmacological activity showed that the matrine matrine,sophoridine and sophoridine derivatives all inhibited the growth of NIH3T3 in vitro,and compound 5g showed the best activity.It provides a research direction for the structural modification of matrine derivatives,and it also contributes to the exploration of anti-idiopathic pulmonary fibers.