Molecular Recognation And Molecular Assembly Of Polyamine Modified β-cyclodextrin With Active Compound Of Tripterygium Wilfordii

As the most important component of the traditional Chinese medicine(TCM)system,traditional Chinese herbal medicine(TCHM)is an important kind of complementary and alternative medicine that derive from ancient China and has evolved over thousands of years.Tripterygizum wilfordii Hook F.(TWHF),a vine like medicinal herb,commonly known as "Thunder God Vine" or "Lei Gong Teng" is a case in point.Traditionally,crude extracts of TWHF have been widely used as a prescription for the treatment of autoimmune and inflammatory diseases.Celastrol(CSL)and triptolide(TPL)are bioactive components extracted from Tripterygium TW,a traditional Chinese herbal medicine that has been extensively tested over the years by regulating multiple molecular targets.Extensive experimentation throughout the years have shown that CSL and TPL exhibit curative properties in the treatment of cancer,obesity,inflammatory,auto-immune and neurodegenerative diseases through the modulation of a variety of molecular targets.Although CSL and TPL are a promising candidate against inflammatory and rheumatic diseases and cancers,systemic toxicity,poor aqueous solubility and low bioavailability hindered its clinical application.In general,in β-cyclodextrins(β-CDs),there are seven D-glucose units linked byα-1,4-glycoside bonds.β-CDs are substances with low toxicity and low immunogenicity,and has been widely applied in the field of biomedicine,especially in pharmaceutical sciences and technology.β-CDs has a torus-shaped structure,thereby possessing the hydrophobic inner face and hydrophilic external face,which allows for varieties of organic and biological guests in hydrophobic cavities.Thus,it may provide host-guest inclusion complexes and supramolecular species in aqueous solution.Herein,we expected to show additional preparations as well as characterization of H2O-soluble inclusion complexes,which were constituted by CSL and polyamine modified CDs with different tethered chain lengths.Our interest is in exploring the binding behavior of polyamine modified β-CDs with CSL,the solubilization effect of CDs on CSL,and the antioxidant properties of the inclusion complexes.Furthermore,it is likely that exploring the above would identify an approach of obtaining a CSL formulation with a high water solubility.At the same time,a supramolecular assembly of polyamine β-CDs polyrotaxane antitumor drugs was constructed,and the structure and properties of the supramolecular assembly-loaded polyrotaxane were studied.The detailed work is as follows:1.Inclusion complexes of three different lengths of polyamine modifiedβ-cyclodextrins(β-CDs)(hosts 1-3)with baicalein(CSL)were prepared by a solution stirring method,and characterized by UV,MS,NMR,SEM,XRD,IR.The results demonstrated that 1:1 inclusion complexes of hosts 1-3 with CSL are present.The binding ability of hosts 1-3 towards CSL increased according to the sequence H1<H2<H3,which was in good agreement with the decreasing chain lengths of these hosts.The hosts 1-3 were able to solubilize CSL to high levels,up to about 50.88 times.In addition,the stability of CSL and their inclusion complexes were determined.The results showed that the hosts 1-3/CSL inclusion complexes were more effective stability than free CSL.This high water solubility and satisfactory stability of the hosts 1-3/CSL complexes will be potentially useful its application as healthcare products and herbal medicine.2.Herein,we present an effective preparation of β-CD-PR by using PPG terminated by alkynyl groups(dialk-PPG,the number average molecular weight of the PPG segment is ca.2000)as the axle,and folic acid(FA)as the end-capping reagent,synthesized a series of polyrotaxanes PR1-3:FA-EN-β-CD-PR,FA-DETA-β-CD-PR,FA-TETA-β-CD-PR,the PR1-3 were characterized by 1H NMR and 2D ROESY.These results indicated that the PR1-3 was obtained.3.A series of novel celastrol-polyrotaxanes(CSL-PRs)with folic acid capped,in which celastrol(CSL)was covalently bound to a cyclodextrin(CD)of the polyrotaxane(PR),were synthesized and were characterized by NMR,XRD,TG and DSC.Our interest is in exploring the solubilization effect of PRs on CSL,and the release properties of the PR1-CSL,PR2-CSL and PR3-CSL.Furthermore,it is likely that exploring the above would identify an approach of obtaining a novel CSL formulation with a high water solubility and good release properties.4.A series of novel triptolide-polyrotaxanes(TPL-PRs)with folic acid capped,in which triptolide(TPL)was covalently bound to a cyclodextrin(CD)of the polyrotaxane(PR),were synthesized and were characterized by NMR,XRD,TG and DSC.Our interest is in exploring the solubilization effect of PRs on CSL,and the release properties of the PR1-TPL,PR2-TPL and PR3-TPL.Furthermore,it is likely that exploring the above would identify an approach of obtaining a novel TPL formulation with a high water solubility and good release properties.