Design,Synthesis And Biological Evaluation Of Podophyllotoxin Derivatives

Podophyllotoxin as an antitumor aryltetralin natural lignin exist in podophyllum of Berberidaceae.Podophyllotoxin exhibiting pronounced antineoplastic and antiviral properties is concerned by more and more researchers.Their derivatives etoposide and teniposide has been used as anticancer drugs in clinical.However,its current therapeutic use is hindered by side effects associated with myelosuppression,neutropenia,nausea,drug-resistance,and poor water solubility.Our group has been devoted to the structural modification of podophyllotoxin for many years,and has synthesized a lot of podophyotoxin derivatives to expect get efficiency and low toxicity of anticancer drugs.Four series of podophyllotoxin derivatives were designed and synthesized based our group research.A series of heterocyclic amine methyl derivative were designed and synthesised according Lipinski's rule of five.B series of 4 'phenolic hydroxy derivative,were designed and synthesized to expect to be able to improve drug absorption and antitumor activity.C series of furan methyl amine derivatives were designed and synthesised.D series were designed and synthesized to amide derivatives of podophyllotoxin.Four series are based on 4 ?-amino podophyllotoxin as raw material.A series was obtained by formed Shifft and reduction.B series was synthesized through the formation of halides with phenolic hydroxyl ether linkage.C series was obtained by Mannich intermediate regime.D series was mainly prepared by condensation of the amino and carboxyl groups.This article is based on our group previous work.Four series were synthesized.All these target compounds were not reported by previous literature.All the structures were confirmed by 1H-NMR,13C-NMR and HR-ESI-MS.The antitumor activity against human cancer HeLa,K562 and K562/A02 has been tested by MTT assay.The result indicates that part of series A have a higher activity than others.The result of series B is normal,and most of series C give a good activity.Compounds of series D show a certain regular significance of anti-tumor activity.This article discusses the preliminary structure-activity relationship,lay the foundation for future research.