Study On The Design, Synthesis And Antitumor Activity Of New Microtubule Inhibitors

Cancer has become the second leading cause of death to human beings and severely threatened health and life of humankind. The current using chemotherapeutic drugs have some drawbacks such as low efficiency, high toxicity and absorption problems. So experts all over the world are sparing no efforts developing new preventing and treating agents.Recently, microtubule-targeted drugs are one kind of the most effective anti-cancer agents. However, the most clinically used tubulin inhibitors at present come from nature products directly or indirectly just as Taxanes and Vincas. Furthermore, the side effects and drug resistance of these products prevent their broad using.Noscapine is a naturally occurring phthalideisoquinoline alkaloid derived from opium. It has been used as an antitussive agent, recently researches found that noscapine and its derivatives can interfere tubulin conformation and microtubule dynamics with few side effects and no addiction liability. So noscapine and its derivatives have the potential to be an effective agent for the treatment of human cancers. A series of substituted indole derivatives show potent anti-cancer activity and broad researches have been carried out.Based on the structures and activities of these two kinds of anti-microtubule agents mentioned above, a series of novel N-substituted Noscapines,5-(1-substituent-lh-indol-3-yl)-6-methyl-5,6,7,8-tetrahydro-[1,3]dioxolo[4,5-g]isoquinolines and N-(1-substituent-lH-indol-3-yl)-4-methoxy-5,6,7,8-tetrahydro-[1,3]dioxolo[4,5-g]isoquinolin-6-yl)methanones have been designed. All chemicals synthesized were confirmed by 1H-NMR and MS.The pharmacological test is under going.