抗生素之父：Selman A.Waksman Antitumor Antibiotics 啡等米是第一个氨基精苷类抗生素，它发频淡安了代医华的选核 烯二炔类高效抗肿瘤抗生素 新型导弹抗癌藥物一Mylotarg Pizer 卡奇意素 Epothilones A and B The Synthesis Race Is On 人及
1 S. A. Waksman isolated it in 1942-3 and received Nobel Prize in 1952. K. A. Folkers determinde its structure in 1948. The First Antibiotic Treatment for Tuberculosis 链霉素是第一个氨基糖苷类抗生素，它发现改变了现代医学的进程。 Streptomycin S. A. Waksman Albert Schatz O O OH O O OH HO HO HO HO OH OHC NH NH2 HN HN H2N NH NHMe 抗生素之父: Selman A. Waksman Antitumor Antibiotics Antitumor Antibiotics 丝裂霉素 C 阿霉素 更生霉素 博来霉素 The calicheamicins are a class of enediyne antibiotics derived from the bacterium Micromonospora echinospora, with calicheamicin γ1 being the most notable. heamicin γ1 and the related enediyne esperamicin are the two most potent antitumor agents known. 烯二炔类高效抗肿瘤抗生素 S Me O I O O OH OMe OMe O OH O N H O O O H Me N MeO O NHCO2Me HO MeSSS Me MeO Me HO Me HO H Calicheamicin γ1 卡奇霉素 1980s 德克萨斯州 公路旁的石头 烯二炔环 新型导弹抗癌藥物—Mylotarg® Micromonospora echinospora 卡奇霉素 辉瑞 埃坡霉素 Epothilones A and B Advantages over Taxol：1) Highly effective against Taxol resistant strains. 2) Structure more manageable and simple. 3) Fewer side effects. 4) The epothilones are more water soluble than Taxol O O HO O R O N S OH Epothilone A R=H Epothilone B R=CH3 Myxobacteria 1993 非紫杉类抗微管蛋白聚合类抗肿瘤药物 The Synthesis Race Is On
Cyclosporine彻底改变了器官移植的面貌 伊维菌素：高尔夫球场的发现 雷帕霉素一新一代免疫抑制药 可德家 “之路” 大量Y 73 her 17种世界公认的柄物 复活节岛的真不老药Rapamune国 Animals Are Highly Skilled Chemists
2 Cyclosporine Cyclosporine 彻底改变了器官移植的面貌 Tolypocladium inflatum多孔木霉 Sir Roy Calne Jean Francois Borel Hartman Stähelin 1969 1983 柏克利酸 Berkelic Acid 在距离美国蒙大拿理工学院校园不远处的荒废的柏克利露天矿坑 (Berkeley Pit)内，是一条流淌着有毒液体的湖泊。湖水高度酸性，酸度达到 pH 2.5, 里面处处是重金属，长满了奇异的菌类。唐•斯蒂尔勒和安德里亚• 斯蒂尔勒(Andrea Stierle)在2006年在那里发现一种微生物可以产生具有救命 潜力的化学物质-柏克利酸(Berkelic Acid)可能是治疗卵巢癌的良药。 . 2006 来自废弃矿坑的发现 伊维菌素:高尔夫球场的发现 WHO列为防治河盲症特效药, 每年7000万人用 Invermectin 1973 Ivermectin 17种世界公认的药物 阿维菌素 伊维菌素 雷帕霉素—新一代免疫抑制药 Rapamycin 雷帕霉素是1975年加拿大Ayerst试验室Vezina等从南太 平洋Easler岛土壤样品中分离的吸水链霉菌(Streptomyces hygroscopicus) 所产生的一种含氮大环内酯类免疫抑制药。1989年Morris等首次将其用 于抗器官移植排斥反应，发现对外周血单核细胞的有效抗增殖作用比环 孢素(C17A)强50-500倍，肾毒性比环孢素低。1999年应用于临床。 “神秘之岛” Streptomyces hygroscopicus Dr. Suren N. Sehgal 复活节岛的真不老药 Rapamune® O O OH O N O O O H OMe O HO H MeO MeO HO Rapamycin 雷帕霉素 比环孢素强50～500倍 1999年应用于临床 Animals Are Highly Skilled Chemists Animals Are Highly Skilled Chemists O O O HO OH OH AcO AcO Fireflies Vinegaroon OH O OH O Acetic acid Octanoic acid Lucibufagin
Animals Are Highly Skilled Chemists Magainin滑爪蟾素 抗蓝肽(antimicrobial peptide) 9。下 Buprestin A Cantharidin 宽整素 Animals New Source of Drugs From Epibatidine To ABT-594 Will animal toxins hold the key for pain relief? Epibatidine 地辣蛙察强线痛 "Cr ABT-594 Cilazapril Hypertension,congestive heart failure 心出 225H ABT-594 was discovered to be 50 times more potent than morphine in 1998, 225H离子通道阻海剂被用作止痛药 yet on animal tests,no paralysis or depression of muscle action was observed. Strauss E.Seience,1998,279,32-33. Batrachotoxin Batrachotoxin箭毒蛙春素 Batrachotoxin (Phyllobates aurotaenia 箭海娃毒素 毒縹蛙 D.aly 毒灵 Batrachotoxin as a tool to study voltage-sensitive sodium channels of excitable membranes which is a selective activators of odium channels. 250-fold more toxic than stryehnine 3
3 Cantharidin 斑蝥素 O O O O O O O HO HO HN NH NH Buprestin A Animals Are Highly Skilled Chemists Animals Are Highly Skilled Chemists O O O O Magainin 滑爪蟾素 NH NH O O NH H2N O NH O NH O NH2 O N O NH H N NH O NH O H2N NH O O H2N H N O HN O H N H2N O NH O H N O HN H N NH O OH H N O O HN S HN O NH2 HN O OH O O H2N O O NH 抗菌肽(antimicrobial peptide) N N H Cl H Epibatidine 地棘蛙素-强镇痛 Strauss E. Science, 1998, 279, 32-33. . Cilazapril Hypertension, congestive heart failure 225H离子通道阻滞剂-被用作止痛药 Animals Animals ：New Source New Source of Drugs of Drugs N N O OH O N O O Me H N H 225 H Epipedobates tricolor N O Cl N N H N H Cl H ABT-594 ABT-594 was discovered to be 50 times more potent than morphine in 1998, yet on animal tests, no paralysis or depression of muscle action was observed. From Epibatidine To ABT-594 Will animal toxins hold the key for pain relief? 地棘蛙素 Dr John Daly Batrachotoxin (Phyllobates aurotaenia) Batrachotoxin Batrachotoxin as a tool to study voltage-sensitive sodium channels of excitable membranes which is a selective activators of sodium channels. 蟾蜍 蟾毒灵 箭毒蛙毒素 O O N HO O O NH HO H O O HO OH Batrachotoxin 箭毒蛙毒素 毒镖蛙 Dr. John W. Daly 250-fold more toxic than strychnine (1933-2008) O O N HO O O NH HO H