Studies On The Synthesis Of5-(Furnan/Thiophene-2-yl)-4-thio-(2’-deoxy) Uridine And Biological Activity

UVA/4-thiothymidine is a novel method of treating cancer, which has low toxicity andhigh selectivity for the potential treatment of cancer, particularly for skin cancer and otherlight sensitive cancers. In UVA/4-thiothymidine therapy, it is urgent to develop aphotosensitizer with a longer wavelength, so as to research and select highly sensitivethymidine analogues as anti-cancer drugs. In order to obtain photosensitizers of visible orinfrared region, near infrared region, we introduced furnan-2-yl, thiophene-2-yl,Nitrofurnan-2-yl, Nitrothien-2-yl into the five position in base uracial for uridine and2’-deoxyuridine, synthesized a series of longer wavelength4-thiothymidine analogues andexplored their biological activities in this paper.Based on uridine,2’-deoxyuridine,2-(Tributylstannyl) thiophene and2-(Tributylstannyl)furnan as the starting material,5-aromatic heterocyclic-(2’-deoxy)uridine can be obtained byStille palladium-catalyzed cross-coupling reaction. Through the method of phosphoruspentasulfide sulfur carbonylation of four poisition, we synthesized a series of wavelengthslonger5-aromatic heterocyclic-4-thiothymidine analogues. The related compounds werecharacterized by1H NMR,13C NMR, IR, UV and MS, we also discussed their NMR, IR andUV spectral characteristics.The interactions between5-methyl-4-thiouridine and human serum albumin (HSA) wasinvestigated by utilization of UV-visible absorption spectroscopy, fluorescence spectroscopy,circular dichroism spectroscopy and molecular modeling. As a result, fluorescencespectroscopy showed that the5-methyl-4-thiouridine effect of HSA was static quenching,thermodynamic data and molecular docking model showed that the main force between5-methyl-4-thiouridine and HSA was hydrophobic interaction, and that5-methyl-4-thiouridine did not effect on the secondary structure of HSA.A preliminary selection for5-(thiophene/furnan-2-yl)-4-thiouridine analogues on mousemelanoma cells anti-tumor activity was investigated by MTT, the results showed that5-(thiophene-2-yl)-4-thiouridine has a good inhibition of cancer cells. Further Study of5-(thiophene-2-yl)-4-thiouridine on human melanoma cells and human colon cancer cells wascarried on, we found UVA/5-(thiophene-2-yl)-4-thiouridine on cancer cell had efficientinhibition of cancer cells. The results show that5-(thiophene-2-yl)-4-thiouridine could beused as a potential anti-cancer drug and would have a good application prospect in cancertherapy.