Design,Synthesis And Anti-Inflammatory,Anti-Tumor Activation Of β-Carboline Alkaloids Derivatives From Picrasma Quassioides

There is a certain connection between inflammation and cancer,and both can occur simultaneously or sequentially.On the basis of inflammation,cancer may occur.Research has found thatβ-carboline alkaloids extracted from Picrasma quassioides have various biological activities,such as anti-inflammatory and anti-tumor,which inspires more researchers to further explore this alkaloid.Based on network pharmacology and computer-aided drug design,our research group plans to use carboline alkaloids as the mother nucleus.Based on the principle of active skeleton assembly,Michael type receptors are introduced into the mother nucleus to obtain natural products with higher activity.In this experiment,two series of compounds are synthesized and their anti-inflammatory and anti-tumor activities are measured.The results of Griess experiment showed that compounds 1a,3a,4a,9a,10a and 14a had certain inhibitory activity on NO release from mouse macrophages;Compound 2a has the best inhibitory effect on NO,with a higher inhibitory rate than the positive control group.The MTT experimental results showed that compounds 4a and 6a-10a had the most significant inhibitory effect on MCF7,with inhibition rates of96.77%,95.32%,95.96%,93.75%,96.49%,and 94.36%,respectively;Compound 8b has the highest inhibition rate on Hep G2,reaching 88.84%;At drug concentration of100μM,compounds 2b and 5b showed significant inhibitory effects on TC1,with91.15%and 95.17%,respectively.Compounds 4a,10a,5b,and 8b may have a broad spectrum of anti-tumor activity.The IC₅₀ value of compound 9a for MCF7 is 15.34μM,showing good inhibitory activity.It is speculated that the N-2 position contains a conjugated anisole structure,while the N-9 position is linked to a conjugated aromatic structure,which can enhance the broad-spectrum anti-tumor effect of the compound.In summary,this topic has designed and synthesized 27 drugs based on network pharmacology and molecular docking technologyβ-carboline compounds provide a foundation for the synthesis sites and subsequent development and research of drug modification of these compounds.By exploring theβ-carboline alkaloid derivatives,with their anti-inflammatory and anti-tumor biological activities,provide the theoretical and experimental basis for the development of new anti-inflammatory and anti-tumor drugs of this type.