Preparation And Characterization Of A Coumarinyl Photoremovable Propecting Group Based Camptothecin Prodrug

Large molar absorption coefficient,fast photodegradation and good stability are the advantages of coumarin-based photoremovable protecting groups(PPGs),on the other country,it has the disadvantages of poor solubility and biocompatibility,low bioavailability and so on.In this paper,we synthesized and characterized a series of new indenocoumarin PPGs after many reactions,which including methylation,acetylation,Bayer oxidation,hydrolysis,Pechmann reaction,allylic oxidation,and reduction reaction etc.However,during the synthesis process,it was unexpectedly discovered that the rearrangement products caused by the unreported fluorene ring skeleton migration occurred in the Pechmann reaction.After experimental verification,we proposed a possible rearrangement mechanism.The photoresponsibility and applicability of the novel indenocoumarin PPGs were discussed by synthesizing template compounds with five different aromatic acids.As the results showed,the protected aromatic acid can release nearly 80% aromatic acid within 30 minutes after being irradiated with a UV light source of 365 nm and 50 mw,which proved the new indenocoumarin PPGs have excellent photoresponse and applicability.In this paper,the antitumor drug camptothecin was selected as the research object,and a photoresponsive anti-tumor prodrug IC-CPT was prepared by the new indenocoumarin PPGs.It was found that the photoresponsibility of the IC-CPT was good in the UV light source of405 nm and 15 mw.Under the light source,60% of the original camptothecin can be released in 6 minutes.Then,using breast cancer 468 cells to perform IC-CPT in vitro cell experiments,the results showed that: cell survival rate of 1 μmol / L of IC-CPT was 92% when light was off,and the cell survival rate was 46% after irradiation;The cell survival rate in the dark group was significantly higher than that of irradiated group,which indicated that the IC-CPT has higher cytotoxicity than its counterpart after light irradiation.It proved that the IC-CPT is a potential photoresponsive anti-tumor prodrug.