Study On The Structure-activity Relationship Of The Photosensitive Anti-tumor Activity Of A Series Of Polyamine Phthalocyanines

Photodynamic therapy(PDT)is an innovative medical method through the photochemical reaction for the treatment of tumor.Phthalocyanine(Pc)has received extensive attention due to a fairly good light and temperature stability and the strong absorption wavelength.Expecially,multi-amine phthalocyanine becomes the hotspot of the ideal photosensitizer research for its natural tumor targeting and cell selectivity.The study of structure-activity relationships between chemical structure designing and its antitumor activity in vitro may contribute more to revealing its influence on the activity.Thus,this research can provide theoretical background for the design of multi-amine phthalocyanines.In this paper,the influence of multi-amine phthalocyanine structures on the safety of drugs,the intake rate of tumor cells,the production of reactive oxygen species(ROS),the morphologic changes and the nucleus chromosomes changes of tumor cells have identified through the UV spectrophotometry,fluorescence spectrometry,2’,7’-Dichlorofluorescin diacetate(DCFH-DA)fluorescence probe method,Hoechst 33342 nuclear chromatin changes method and the thiazolyl blue tetrazolium bromide(MTT)method.The main results are as follows:(1)When the side chain structure of multi-amine phthalocyanine is nonionic,hydrochloride and quaternary ammonium salt structure,the hydrochloride structure of benzylamine phthalocyanine has the strongest photosensitive antitumor activity.The reason is that the chlorine atom can inhibit the generation of fluorescence,thus the generation ability of ROS has notably increased.Conversely,the quaternary ammonium salt structure can effectively block the photoinduced electron transfer reaction,so that the drug activities are remarkably increased.Thus,the photosensitive antitumor activity of the quaternary ammonium salt structure of aniline phthalocyanine is best.(2)By researching the light-sensitive antitumor activity of multi-amine phthalocyanine with the side chain structure containing heavy atom,it is found that the iodine atom can effectively enhance the generation ability of ROS due to the existence of heavy atom effect.Thus,the side chain structure containing iodine atom of multi-amine phthalocyanine has the strongest photosensitive antitumor activity.(3)By researching the photosensitive antitumor activity of multi-amine phthalocyanine with the increasing number of side chain carbon atoms around the nitrogen atoms,results show that with the increase of the number of side chain carbon atoms around the nitrogen atoms,the spatial structure of multi-amine phthalocyanine increases gradually.Meanwhile,the larger structure can effectively improve the molecular aggregation of phthalocyanines and thus the intake ability of tumor cells enhances.Therefore,there exists the highest photosensitive antitumor activity.(4)By researching the photosensitive antitumor activity of multi-amine phthalocyanine with the increase of the number of side chain nitrogen atoms,findings show that the increase of the number of side chain nitrogen atoms can effectively improve the water solubility of multi-amine phthalocyanine.And it can restrict the molecular aggregation of multi-amine phthalocyanine,thus,the photosensitive antitumor activity can obviously increased.Above results show that the structural changes of multi-amine phthalocyanines and them photosensitive antitumor activity have the inseparable relations.And the photosensitive antitumor activity is positively correlated with the generation ability of ROS and the intake ability of tumor cells.The regular of the structure-activity relationships can provide an effective guide to design and synthesis the new multi-amine phthalocyanines that have better photosensitive antitumor activity,but also for further laying the foundation to screen the multi-amine phthalocyanine owning an important clinical application value.