The Preparation Of Naphthoquinone Derivatives And Study On Their Antitumor Activities

Naphthoquiones are small molecular compounds existing in the nature, which have multiple bioactivities. Based on the great interest on naphthoquiones, people synthesized a lot of derivatives and carried on research on their antitumor activities, the mechanism and structure-activity relationships. Our research focused on the naphthazarin ( 5,8- dihydroxy -1,4- naphthoquinone ) compound -- shikonin.The electrophilicity of naphthoquinone ring can be responsible for the activity since cellular nuclophiles can react with naphthoquinones. Besides, the previous study in our laboratory indicated that the naphoquinoecore is indispensable. Among all the compound we tested before, the protective 1,4,5,8- tetromethoxynaphqthoquinoe (TMNQ) were totally inactive. Among the deprotective compounds, the 6- substituted were more potent that the 2- substituted. Especially the 2-(1- butylsulfanyl-ethyl) -5,8- dimethoxy -1,4- naphthoquinne showed potent activity against cell P388.On the base of reported structure-activity relationship (SAR) and our previous work, 2- or 6- substituted 5,8- dimethoxyl -1,4- naphthoquinone derivatives contained sulfur are designed as the candidates of antitumor agents. 30 target compounds were synthesized and characterized by 1HNMR, all of which are novel. The antitumor activities of all these compounds on cell BEL7402、HT-29 and SPC-A-1 were tested, and all of them have antitumor activities. Especially the 6- substituted 5,8- dimethoxyl -1,4- naphthoquinone derivatives have excellent activities. In addition to the low toxicity of this kind of compound, it deserves studying further.