Charles Best and Edward Clark Noble 88 Best friends and Teammates Best friends and Teammates Noble later played a small but critical role in the most important Canadian contribution to cancer chemotherapy research:the discovery of vinca alkaloids by his brother Robert Laing Noble.Although one might expect that a physician involved in 2 of Canada's most important medical discoveries during the 20th century must be famous,such was not Clark Noble's fate
How Do Vinblastine and Vincristine Work? Alpha tubulin Vinca alkaloids Beta tubulin Taxanes prevent prevent microtubule microtubule assembly. disassembly. One of the most important Canadian contributions to cancer research during the 20th century.The National Cancer Institute of Canada named its most prestigious award for excellence in cancer research the Robert L.Noble Prize in honour of this discovery
长春花属生物碱衍生的五个著名抗癌药物 红色区城 无系统性研究 OMe 甲就恭取代 (长表新) Me 16 HO H 缩碳入元环 (长春瑞) Me MeO2C AcO" OH 酰胺取代甲酯、 二氟取代， 无乙酰基 (+)-Vinblastine 无羟基 (长森地判 (长衣花碱) (长泰氧分 上世纪60年代，从夹竹桃科植物长春花中分离出来的长春花碱(vinblastine)和 长春新碱(vincristine),很快便成了礼来(Eli Lilly)公司开发上市的两个著名抗癌 药物—长春花碱主要用于治疗膀胱癌和乳腺癌，长春新碱主要用于治疗急性白 血病和淋巴癌
从Khellin凯林到硝苯地平 Khellin凯林1879年 Nifedipine硝苯地平 钙通道阻滞剂一高血 压、心绞痛、冠心病 拜耳公司F.Bossert 阿密芹Ammi visnaga 合成了2000个衍生物 1961合成胺碘酮amiodarone 钾通道阻滞剂用于心律失常 在埃及khella果实中含凯林(Khellin),用于治疗冠状动脉性疾病，如 狭心症、冠状血栓症等。欧洲民间用本植物医治尿泌系统疾患和通经
“疾病之王”糖尿病 Sir Harold Percival Himsworth 减少吃 油、糖、盐类 (1936年1型和2型糖尿病的区别 Elizabeth Hughes 吃适量 奶品类 肉、鱼、蛋及豆类 瓜菜类 吃多些 水果类 1型糖尿病：自身免疫系统 2型糖尿病：代谢疾病 吃最多 五谷类
山羊豆碱 Galegine H2N、NH2 NH French diabetologist Galega officinalis Jean Sterne
John M.Daly博士-蟾蜍毒素之父 OH HO HO batrachotoxin batrachotoxin A 'Frog Man‘ John William Daly (1933-2008) Golden poison frog,The most toxic of poison dart frog species is Phyllobates terribilis Daly (r)poses with former postdoctorul fellow Kenneth Seamon in 1983,shortly after they discovered that forskolin was a powerful research tool
Batrachotoxin箭毒蛙毒素 HO HO John William Daly Phyllobates terribilis Isolated,purified,and characterized (1933-2008) in 1963;structure was determined in 1968 金色箭毒蛙(Golden Poison Frog)是箭毒蛙 中毒性最强的一种，它的身体没有一个瓶盖大， 但其毒性却足以杀死20000只老鼠或10个成年人。 Bernhard Witkop (1917-2010)
Batrachotoxin箭毒蛙毒素 HO HO HO HO Batrachotoxin A Batrachotoxin 箭毒蛙毒素(BTX)是1963年美国NIH科学家John W.Daly (1933-2008)和Bernhard Witkop(1917-2010)从哥伦比亚北部雨林毒蛙 分离出的，1968年通过X-衍射确定了batrachotoxinin A的结构，通过 比较二者的核磁谱和质谱数据，1969年确定了箭毒蛙毒素的结构
Where Did Our Drugs Come From? New morphine comes from frogs Epibatidine The skin of the phantasmal 地棘蛙素 poison frog contains epibatidine 'Frog Man Amphibian skin has provided a wide range of biologically active alkaloids.During the past 30 years,>400 alkaloids of>20 structural classes have been detected by Daly.Total 800 Amphibian alkaloids reported. Epibatidine was discovered by John W.Daly in 1974.The structure of epibatidine was elucidated in 1992.About 28 structural classes of alkaloids are known in poison frogs