The Study Of Design, Synthesis And Anti-tumor Activities Of Aspirin Derivatives

Recently, cancer has become one of most dangerous diseases that threaten public and human health. Moreover, for the reason that the incidence of cancer had been increasingly higher, cancer will become the most deadly disease in the future. More and more surveys has shown glycosaminoglycan (GAGs) is closely associated with cancer, and GAGs’properties will influence tumor tissues’growth and development. Because there are many different functional groups link to GAGs, so GAGs will present various biological properties when they are linked with different proteins. Currently, chemotherapy was one of the common therapy that being used in cure cancer. However, chemotherapy is not only harmful for tumor but also for normal tissues. This defect has limited the use of chemotherapy. And other drugs that have been used in cancer are always too expensive to afford. Therefore, exploring for a high efficiency, low toxicity and cost anti-tumor drug is an important goal for scientists.Aspirin is one of the most useful drugs in human history which has been used for over 100 years. There had been huge numbers of researches about Aspirin until now and we have developed various clinical uses. Furthermore, more and more new biological acitivities of aspirin had been uncovered by scientists’ deeper researches. Aspirin has shown surprising well anti-tumor activities which made it become a hot spots for develop new anti-tumor drugs. The anti-tumor mechanisms for aspirin is complex but there are some mainstreams. For instance:suppress cyclooxygenase and transcription factors, activate protease and so on. And some newly synthesized aspirin derivatives had shown incredible well anti-tumor activities.In order to achieve high efficiency, low toxicity and cost anti-tumor drugs, we chose aspirin as a core compound and modify its structures. We focus on the well activities of aspirin and GAGs to design our target compound. Therefore we hold the ethanoyl group of aspirin and add cation groups. We utilize carboxy group on aspirin via condensation and substitution reactions to add positive functional groups such as amino.guanidine and tetramethyl thiourea groups. All target compounds are verified by nuclear magnetic resonance and mass spectrometry.We have tested some of target compounds’inhibitory activities against A549 and H1299 cancer cell lines in vitro. And these target compounds show much better inhibitory activities than aspirin. Besides we have found a structure-activity relationship from our results. The linkage between aspirin core and functional is important which higher and the derivatives’inhibitory activities will better. This discovery will benefit further research on these kinds of aspirin derivatives.