Synthesis And Studies Cytotoxic Activities Of Ferrocene Carboxylic Acid, Mellow, Ester

Ferrocene and its derivatives have strong anti-cancer activity. At present, they have been used widely in the field of pharmaceutical synthesis and clinical applications. This paper studies the carbon chain on the activity of ferrocene and analyzes its structure-activity relationship. Based on this, Three parts are contained in this article as follows:1. In order to study the structure and properties, we first need to synthesize series of ferrocene carboxylic acid (la～6a), alcohol-phenol (1b～8b), ester (1c～8c). (1)In the process of synthesis, the Suzuki reaction in view of the traditional drawbacks and deficiencies, improved the Suzuki reaction, a higher yield synthesis of the two kinds of ferrocene alcohols 6b and 7b. It is the method of the intermediate products of ferrocene boric acid because of easily obtained, simple and low toxicity. So, it is very convenient way of Suzuki reaction to the introduction of other ferrocenyl new material. (2) They was synthesized to the eight products of ferrocenyl esters of 13-cis-Retinoic Acid (lc～8c) by Mitsunobu reaction. Mitsunobu reaction not only inherite the advantage of the DCC/DMAP method which is mild reaction conditions can maintain the advantages of configuration, but also overcome the reaction defects of long times, multi-product, difficult to separate the product.2. By comparing the three main test methods of vitro cytotoxicity, MTT method is used because of its fast and simple, no special test equipment, no radioactive, sensitive, and economic characteristics. We test cytotoxic activities of twenty kinds of the synthesis of ferrocene carboxylic acid (la～6a), alcohol (1b～5b), ester (1c～8c) and 13-cis-Retinoic Acid on lung cancer cells (A549), hepatoma cells (BEL7404) and tongue cancer cells (Tca) using MTT method. According to the data of drug activity by MTT method, we calculat the IC50 value.The results show that:ferrocene carboxylic acids, alcohols, esters have anti-cancer activity and a certain regularity.3. Their structure-activity relationships are analysized and discussed according to the measured data of cytotoxic activity of ferrocene carboxylic acids, alcohols, esters. (1) There is entirely different biological activity that the similar compounds because of its substituents and substituted positions. (2) The cancer cells have certain anti-cancer activity for ferrocene carboxylic acid, alcohol, ester and 13-cis-Retinoic Acid. The factors affecting on the anti-tumor activity includ the length of carbon chain, aromatic, carbonyl, electronic effects of hydrophobic and hydrophilic groups space effect. (3) Different types of compounds reflect the different anti-cancer activity:ferrocene carboxylic acid is superior to ferrocene alcohol that is better than ferrocene ester and 13-cis-Retinoic Acid.