Study On The Sulfonate Reaction Of4-thiothymidine Analogues Under Microwave Irradiation And Its Activity

Nucleotide compounds, which have various biological activities, have gained more andmore attention for their wide applications in biology and medical care since1950s and1960s.Meanwhile they have played an important role in the therapy of cancer, AIDS (HIV),hepatitis B (HBV) and anti-cancer.So it is significant to make further chemical modificationfor the ucleoside analogues that have clinical and potencial applications.In this article, we mainly explore the synthesis of4-thiothymidine analogues withmicrowave irradiation and their characterization and application in medical care.4-Thiothymidine analogues are firstly synthesized under microwave irradiation, which provedto be an efficient way. The structure is characterized by IR, UV-vis, HRMS,1H NMR and13CNMR spectrometry. Meanwhile, the spectrum features of thymidine analogues and4-thiothymidine analogues are studied and compared to explore the cause for the changes.The results show that4-thiothymidine analogues have an important feature of spectrum,which provid some basic information for further study on anti-cancer drugsIn order to establish the3-D structure of the thio-containing nucleoside and nucleosite,4-thio-5-iodouridine is analysized by X-ray crystallography. The results show that there aretwo different conformations of4-thio-5-iodouridine molecules in the unit cell and it isconfirmed that the sulfur atom in nucleoside is substituted in4-position and belong to theβ-configuration through the X-ray analysis, which lie an important foundation for the study ofnucleoside and nucleic acid structure and biological function.The interactions between4-thio-5-iodouridine and human serum albumin (HSA) areinvestigated by fluorescence spectroscopy. The results show that4-thio-5-iodouridine has astatic fluorescence quenching on human serum albumin (HSA). It is determined that the mainforce between4-thio-5-iodouridine and HSA is typical hydrophobic interaction by annalyingthe thermodynamic data. In addition, the effect of4-thio-5-iodouridine on the secondarystructure of HSA is investigated by circular dichroism. The results show that4-thio-5-iodouridine had no effect on the secondary structure of HAS.By the method of MTT, study the inhibition rate of4-thio-5-iodouridine for MCF-7Theresults show that4-thio-5-iodouridine can kill cancer cells and has potential anticanceractivity.