Synthesis And Anticancer Study Of Bola Quercetin-lipid Conjugates As Drug Self-delivery System

Bolaamphiphilic molecules are compounds which contain two hydrophilic head groups connected via a hydrophobic chain.Thanks to their unique structure and characteristics,the bolaamphiphiles are able to form various hierarchically stable self-assemblies at the interfaces and in solutions hence to be applied as functional materials,such as drug delivery carriers.Drug self-delivery means that the drug itself can form nanosize self-assemblies as delivery system to transport the drug to the target tissues.Compared to the traditional?carrier-assistant?drug delivery system,the drug self-delivery system has been granted with higher drug loading,less adverse effect thanks to be free of additional carrier.Quercetin is a kind of flavonoids widely available from natural sources.It possesses of various pharmacological activities,such as anti-tumor,anti-virus,antihypertension and anti-inflammation etc,therefore to attract more attention in medicinal and pharmceutical research.In the work of this thesis,taking the unique structure of bola compound and the bioactivity of quercetin,a series of bola quercetin-lipid conjugates have been designed,synthesized and characterized by ¹H-NMR,¹³C-NMR and MS etc.Then the antiproliferation activity of these synthetic compounds were evaluated on various cancer cells,which demonstrated the importance of the bola structure and the hydrophobic chain length on the antitumor activity of the bola compounds.Moreover,these compounds could downregulate the expression of HSF1 and Bcl-2,indicating their ability to fight against drug resistance and induce apoptosis.Then we studied the self-assembly of these bola lipid-quercetin conjugates and assessed their ability to form the drug self-delivery system.In summary,we developed a series of novel bola quercetin-lipid conjugates,which not only exhibited potent antiproliferative activity against cancer cells and induced apoptosis,but also possessed promising self-assembly ability to construct drug self-delivery system.Our studies therefore highlighted the great potential of these compounds for future application in treating cancer and other life-threatening diseases.