Studies On The Synthesis And Bioactivities Of Organoselenium-sugar Derivatives

In the known elements, fluorine atoms of the electronegativity is the largest. The Van der Waals radium is close to the hydrogen atom. The medicinal chemists have become more and more conscious that the biological effect of some organic compounds may produce subtle changes through introducing fluorine or fluorinated substituent into their structures. The application of fluorination in drug design and development are summarized from the viewpoints of electronic effect, metabolic, block and lipophilicity.In the development and progression of cancer, FAK is a key regulator of survival, proliferation, migration and invasion. It plays an important role in signal transduction pathways. Selenium is one of the essential microelements in human body. Since selenium has been found, more and more chemicals are applied to the study drugs. It has been proved to be able to inhibit the proliferation and migration of tumor cells. When the selenium was modified by carbohydrates, the compounds showed improved bioavailability, lowered toxicity and side effects. According to this, a series of oranoselenium-sugar derivatives substituted by fluo or methoxy were synthesized and their bioactivities were evaluated.Speculated that the initial structure-activity relationship was that : (1)The bioactivity of the organo-selenium compounds can be improved by carbohydrate units. (2)Selenium is an essential element to the activities of the compounds. (3) The 2 position of benzisoselenazolones connected with rigid groups such as benzene can decrease the activity. (4) The acetylation of the sugar unit can enhance the activity of organo-selenium sugar compounds.Based on the structure-activity relationship, a series of organoselenium compounds were designed. It was an efficient and simple synthetic strategy that the selenium compound was firstly coupled with sugar. Substituted 2-(Chloroseleno)benzoyl chloride synthesised with the amino compounds by ring closing reaction and characterized by NMR and MS. FAK enzyme inhibitory activitives of the compounds were also studied.The bioactivity of the organo-selenium compounds substituted by methoxyl is higher than substituted by fluorin.