| Muxiang is a traditional Chinese medicinal herb that has functions such as strengthening the stomach,reducing accumulation,regulating qi,reducing depression,relieving pain,and preventing miscarriage.At present,a large number of studies have shown that there are abundant Sesquiterpene lactone ring compounds in the medicinal materials of Aucklandia odora,among which the important natural product molecule is dehydroaklandrin,which has anti ulcer,anti-cancer and antibacterial effects.However,the molecular dehydrocostus lactone of Natural product has some shortcomings such as low bioavailability and weak activity,which is not suitable for direct use as a drug.Therefore,it is necessary to modify its structure and look for new Lead compound.In this paper,the synthesis and bioactivity of multifunctional splice derivatives of Natural product molecular dehydrocostus lactone were studied according to the strategy of superior skeleton recombination.Firstly,according to the strategy of recombination of dominant skeletons,the synthesis and bioactivity of multifunctional splice derivatives of Natural product molecular dehydrocostus lactone were studied.Firstly,the Active ingredient of Aucklandia odora was extracted,separated and purified to obtain the molecular dehydrocostus lactone of Natural product.Then,the dehydrocostus lactone and the core skeleton butyrolactone ring of dehydrocostus lactone were synthesized by using dehydrocostus lactone as the raw material,and the anti-tumor activity of its derivatives in vitro was preliminarily studied.The main research work of this article is as follows:(1)Preparation of 3 and 5 functional group splicing derivatives of dehydrocostus lactone.In this paper,firstly,the extraction,separation and purification of Aucklandia odora were carried out to obtain the Natural product dehydrocostus lactone.Then,14 dehydrocostus lactone oxidized indole pyrrole bisspirocyclic splice derivatives 3 were synthesized by 1,3-dipolar Cycloaddition reaction from dehydrocostus lactone,indigo and proline.Considering that the core skeleton of Natural product dehydrocostus lactone is 3-methylenecyclolactone,and 3-methylenecyclolactone is also the core skeleton of the drug food functional factor pyrethrum lactone,we take 3-methylenecyclolactone,Ninhydrin and proline as raw materials,through 1,3-dipolar Cycloaddition,Synthesis of 31 cyclic lactone spliced ninedione pyrrole type double helix ring splicing derivatives library 5(containing 1 medicinal and food functional factor of small white chrysanthemum lactone spliced ninedione pyrrole type double helix ring splicing derivative 5da;containing 2 tulipin A spliced ninedione pyrrole type double helix ring splicing derivatives 5ga and 5gb;containing 1 woody lactone spliced ninedione pyrrole type double helix ring splicing derivative 5fa),and we can also directly use dehydrogenated woody lactone 2 as a substrate,Synthesis of two dehydrocostus lactone spliced ninedione pyrrole double helix ring spliced derivatives 5.Preliminary anti-tumor activity tests were conducted using MTT method on 47 new types of multifunctional splicing derivatives 3 and 5 synthesized.The results showed that 8 derivatives 3aa,3ab,3ad,3ba,3bb,3bd,5da,and 5ea had good inhibitory activity on K562 cells,and their activity was improved compared to the parent dehydrocostus lactone,especially the biological activity of derivatives 3ab and 5da exceeded that of the positive control drug cisplatin.Therefore,the multifunctional splicing derivatives of dehydrocostus lactone designed and synthesized by us are likely to develop into new Lead compound with anti-tumor effects through further research,which is worthy of further research.This thesis is mainly devoted to the preparation and anti-tumor activity evaluation of multifunctional splicing derivatives of dehydrocostus lactone.The research results are of great significance to the discovery of Lead compound with anti-tumor activity of multifunctional splicing derivatives of Dehydrocostus lactone. |
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