A Natural Anticancer Camptothecin Derivative Synthesis And Activity Of Two Natural Antineoplastic Agents Colchicine Derivatives And Activity

Cancers are one kind of repetitious and familiar diseases which threaten man health.According to the statistical data from WHO in 2003,there were about 10,000,000 patients in the world,6,200,000 patients died of cancers.The patient' number died of cancers is going up every year in our country,so the prevention and therapy are very difficult.Chemical drugs occupied important position in the treatment of cancer,especially for the anti-tumor drug derived from the plant which possessed 40%market rate of overall anticancer medicines.Camptothecin(CPT) exhibited higher anti-tumor activity against many cancers,just mainly by acting on the Topâ… of DNA,so it is an inhibitor of Topâ… .Colchicine interferes with microtubule growth,therefore,affects mitosis and other microtubule dependent functions. Camptothecin and colchicine were used as the lead compounds to do some modifications on their structures,and expected to find new anti-tumor agents with more efficacy and less toxicity.It is very important that new drug with intellectual fights are developed.The results in vitro showed that these CPT uracil-1-acetic acid este derivatives possessed higher cytotoxicity in the MTT assay.This may be related to the intramolecular self-activation of CPT ester.The bases of uracil N~1 mono-alkylating reaction were obtained by the analyzing and calculation in KOH aqueous solution. The cytotoxicity showed that the anti-tumor activity of uracil-1-acetamides should be lost when uracil N~1 was alkylated.It was found that thiocolchicine derivatives have higher anti-tumor activity in vitro in the MTT assay.The results showed that piperazinyl analogues possessed higher activity than amine analogues'.For piperazinyl analogues,longer of carbon chain between carbonyl group and nitrogen atom,lower the activity.However,these derivatives had weak anti-tumor activity in vivo.Total 45 target compounds were prepared during two years,40 of them are new compound.All target compounds were confirmed with ~1H NMR,some of them were corroborated with IR,MS,or HR-MS.All target derivatives were evaluated with MTT assay,some of them were tested by animal tumor model in vivo.