The Studies Of DNA Cross-linking Agents Bearing Bis (Catechol) Moiety And Synthesis Of The Bis (Diazirine) Derivatives

.DNA as the genetic material plays important role in transmission of genetic imformation. The process of transmission can be inhibited by interfering the structure and property of DNA. Therefore, the research of antitumor durgs targeting DNA duplex structure has been a very important part in durg design.DNA cross-linking agents as a series of antitumor drugs can cross-link DNA duplex with covalent bond. The interstrand cross-links prevent DNA strand separation. Thus, it blocks to DNA replication and DNA transcription. If left intact, the interstrand cross-links can lead to cell death. Inducible DNA cross-linking agents can increase the selectivity to the tumor cell.In this paper, five bis(catechol) derivatives were designed and synthesized. We investigated their ability of cross-linking DNA which induced by oxidants.We studied situation of cross-linking between these compounds and linar DNA. Compound 2 and 3 have good cross-linking results which induced by NaIO4. When the concentration of compound 2 and 3 is 50μM, the cross-linking yeild is 100%. The cross-linking ability of compound 2 is better than compound 3 when the concentration is 20μM. When compound 2,3 and 4 were induced by tyrosinase, the cross-linking results were different. Compound 4 obtains the best cross-linking result. We also tested capability of compound 2,3 and 4 cross-linking oligonuleotide acids. The results were the same as the cross-linking linar DNA.The results of UV experiments show us the property of compounds which induced by NaIO4 and tyrosinase is different. And according to the different structure between these compounds, we can explain that these compounds induced by different oxidants have different results in cross-linking DNA. We calculated the structure of the three compounds on the basis of DFT geometry optimization to understand the binding properties of these compounds with DNA.We calculated the structure of the three compounds on the basis of DFT geometry optimization to understand the binding properties of these compounds with DNA. We designed and synthesized bis(diazirine) derivatives:3,3’-(4,4’-dimethoxybiphenyl-3, 3’-diyl)bis(3-(trifluoromethyl)-3 H-diazirine) and N’,N’,N’,N’-tetramethyl-N’,N’-bis(4-(3-(trifluoromethyl)-3 H-diazirin-3-yl)benzyl)biphenyl-4,4’-diaminium bromide.