Regulatory Role Of Flexible Side Chain On The Interaction Between Xanthones And DNA

Malignant tumors are serious diseases endangering human health. With the development ofmolecular oncology, the pathogenesis and progression of human tumors become clear. Thedevelopment concept of anti-tumor drug has been changed from traditional anti-tumor drugsto targeted anti-tumor drugs. DNA and its related enzymes are important targets of anti-tumordrugs. Therefore, the design and development of anti-tumor drug which targeting DNA and itsrelated enzyme are considered as promising ways. In this work, we have chosen Xanthone asthe lead compound, which have good biological and pharmacological activities. And then aseries of xanthone derivatives with amino side chain was synthesized. The interactions ofXanthones with DNA were investigated by spectroscopic methods, electrophoretic migrationassay and polymerase chain reaction test. And the relationship between their effects on cellproliferation and their side chain structure factor was been discussed. The results show that,the flexible amino side chain may tune the binding mode and affinity of Xanthones with DNA.And the amino side chain with different polar may effect the compounds polar, leading toinhibition of tumor cell proliferation showing some differences. The dimethylamino,pyrrolidinyl substituted xanthones exhibit stronger bonding affinity with DNA and moreeffective cytotoxic activity. Furthermore, the inhibitory activity of DNATopoisomerase (Topo)and Taq polymerase also were detected by gel electrophoresis. The results showed that,compounds have no inhibitory effect on DNATopo and Taq polymerase.In addition, several thiochromanones derivatives (CMCT, CMMT and No.51), which havegood anti-tumor activity and saved by our research group, were detected by gelelectrophoresis for the inhibitory activity and mechanism of DNA Topoisomerase. The resultsshowed that CMCT and CMMT were the Top I poisons, and the inhibition of CMCT on Top Iwas stronger than that of CMMT.51had almost no inhibitory effect on Top I. CMCT was theTop II poisons.