Synthesis And Anti-tumor Effects Of Nucleus Dimethyl Shikonin Oxime Side Chain Amino Acid Ester Derivatives

Cancer as a major killer for human beings is eroding the health of human beings with frightening speed.According to the survey in 2012"World Cancer Report",the number of Chinese newly diagnosed cancer cases was 3.07 million,accounting for to 21.8%of the global total,the annual death toll of 2.2 million,accounting for 26.9%of the global total,and the speed of growth is amazing^[1]year after year.Cancer has become the first killer of human health.Lithospermum erythrorhizon as China’s traditional Chinese medicine,has been included in the"People’s Republic of China Pharmacopoeia",and its main function is mainly dried roots^[2].Lithospermum erythrorhizon in clinical medicine is mainly used for a variety of bacteria,fungi bactericidal drugs,at the same time to treat various skin diseases^[3].In recent years,shikonin extracted from Lithospermum erythrorhizon t make people’s eyes to refocus on this traditional Chinese medicine because of its anti-tumor effect.Due to decades of active research,Shikonin has been proved that it has a very broad spectrum of anti-tumor activity.But none of shikonin derivatives has been in clinical as anti-tumor drug because of its pan-cytotoxic.The previous study of our group showed that dimethyl oxime Shikonin structure not only has an effective anti-tumor effect but also has low toxic side effects and high selectivity for tumor cells,but its water solubility is very poor.Therefore,the purpose of this article is to keep the structure of dimethyl oxime Naphthoquinone nucleus and change its side chain to improve its water solubility and study its anti-tumor activity at the same time.First,we connect the carbon chain to hydroxyl of the side chain,and then we connect four kinds of amino acids to hydroxyl of the carbon chain.We synthesize 20 nucleus dimethyl Shikonin oxime side chain amino acid ester derivatives,then study their water-soluble activity by calculation method,at last study its anti-tumor activity by MTT method.These results demonstrate that water-soluble activity of amino acid ester derivatives is better than normal derivatives with alkyl side chains.The anti-tumor activity of amino acid ester derivatives is growing with the growth of the carbon chain and derivatives with 8 carbon atoms chain have the best anti-tumor effect.Glycine ester and valinate ester have the best anti-tumor effect in four kinds of amino acid ester.