2018/10/27 Saturday 地球上杀人最多的动物 MOSQUITOWEEK MOSQUITO-BORNE DISEASES DEET差蚊胺 屠呦呦一青蒿素一诺贝尔奖 “幽幽鹿鸣，一乌惊人” 《诗经·小雅》一一个美丽的预言 嘞嘞鹿鸣，食野之苹。我有嘉宾，鼓瑟吹笙。 嘞嘞鹿鸣，食野之高。我有嘉宾，德音孔昭。 呦嘞麂鸣，食野之芩。我有嘉宾，鼓瑟鼓琴。 1
2018/10/27 Saturday 1 地球上杀人最多的动物 DEET避蚊胺 62 屠呦呦—青蒿素—诺贝尔奖 ——“呦呦鹿鸣，一鸣惊人” 《诗 经 • 小 雅 》——一个美丽的预言 呦呦鹿鸣，食野之苹。我有嘉宾，鼓瑟吹笙。 呦呦鹿鸣，食野之蒿。我有嘉宾，德音孔昭。 呦呦鹿鸣，食野之芩。我有嘉宾，鼓瑟鼓琴
2018/10/27 Saturday 一株小草改变了世界 A Chinese Herb Changed the World ARTEMISININ Qinghaosu Artemisia annua Artemisinin诺华 支装装黄转装款学”动学我洛o 《附后各急方》C:青篱素：源自中苹药国的发现2011 青擒素给构所完诊作组，一种谢型的倍年巷内雕一青葛章。升学運虎19刀，22粉，142 青蒿素结构 脉学通括 风 @XRa 1977 2
2018/10/27 Saturday 2 63 A Chinese Herb Changed the World The newest class of potential anti-malarials are peroxy-bridge containing compounds. 突破了“抗疟药物必须含氮N原子”的医学观念。 Qinghaosu 一株小草改变了世界 青蒿素结构研究协作组, 一种新型的倍半萜内酯——青蒿素。科学通報, 1977, 22(3), 142. Artemisia annua Artemisinin 诺华 《肘后备急方》 Cell：青蒿素：源自中草药园的发现 2011 O O H3C O CH3 H CH3 O O H H 青蒿素结构 科学通報 1977, 22(3), 142 X-Ray
2018/10/27 Saturday 青蒿素结构与诺贝尔奖 南斯拉夫研究人员提出的青需素结构 破端效 盖于青蒿素在酸性条件下的分解产物和在催化直化下的还原产物的 站构特点，1972年，前南斯拉夫料学家在印度召开的第8属天然产物化学国 际研讨会中，提出了一个带过氧桥单元的青蒿素结构。1973TL 青素构研究作,一新型的储字内—青篇。科学通197,23,14265 伊维菌素：高尔夫球场的发现 9 大村智 hi Omura and Willia 篱素198( 热带感染症的克星 3
2018/10/27 Saturday 3 O O H3C O CH3 H CH3 O O H H 65 青蒿素结构与诺贝尔奖 基于青蒿素在酸性条件下的分解产物和在催化氢化下的还原产物的 结构特点, 1972年, 前南斯拉夫科学家在印度召开的第8届天然产物化学国 际研讨会中, 提出了一个带过氧桥单元的青蒿素结构。1973 TL O O H3C O CH3 H CH3 O O H O H O H3C O CH3 H CH3 O O H 青蒿素结构研究协作组, 一种新型的倍半萜内酯——青蒿素。科学通報, 1977, 22(3), 142. 南斯拉夫研究人员提出的青蒿素结构 66 伊维菌素:高尔夫球场的发现 Satoshi Ōmura and William C. Campbell 伊维菌素 1980 大村 智 热带感染症的克星 O O O O O O O O O OH H OH H O HO H H O Ivermectin
2018/10/27 Saturday 阿维霉素与伊维霉素 1979 1981 湘 Omura and William C.Campbel m10列为防治河言症特效药.毫年700万人用 药物源于日常生活 现象（牲富出血死亡）一本质（双香豆素杭凝作用） 失验室（发现双香豆素的化学结构，并合成其衍生物） 一商业（灭赢药） 从动物药一临床应用（口服抗凝药“主”） 4
2018/10/27 Saturday 4 67 阿维霉素与伊维霉素 WHO列为防治河盲症特效药, 每年7000万人用 O O O O O O O O O OH H OH H O HO H H O O O O O O O O O O OH H OH H O HO H H O Avermectin H2 Willkinson's Catalyst 1979 Ivermectin 1981 Satoshi Ōmura and William C. Campbell 药物源于日常生活 现象（牲畜出血死亡）——本质（双香豆素抗凝作用） 实验室(发现双香豆素的化学结构，并合成其衍生物)——商业(灭鼠药) 从动物药——临床应用(口服抗凝药“霸主”)
2018/10/27 Saturday 华法林：从灭鼠药到口服抗凝剂的传奇 化合物的结构鉴定重要吗？ c2 Dicoumarol双春豆 Melilotus,melilot,sweet clover arl Link i 首着草 a一06 A-hvdrovecamati Warfarin and Vitamin K 单法林 Vitamin K 美因第34任总 香豆素类口服抗凝药，通过抑制生素K在肝胜 子、 作用。1用 口服杭凝药物的历史 dicine in 1943 for ardA.D 1895.1976 (1893-1986 5
2018/10/27 Saturday 5 Melilotus, melilot, sweet clover 苜蓿草 O O OH O O OH Dicoumarol 双香豆素 Karl Link in his laboratory O O OH O O O O OH OH O O coumatin 4-hydroxycoumatin dicoumarol H H O 华法林:从灭鼠药到口服抗凝剂的传奇 化合物的结构鉴定重要吗？ Warfarin and Vitamin K O O CH3 R O O OH O Henrik Dam (1895-1976) Edward A. Doisy (1893-1986) 香豆素类口服抗凝药，通过抑制维生素K在肝脏 细胞内合成凝血因子Ⅱ、Ⅶ、Ⅸ、Ⅹ，从而发 挥抗凝作用。1955年，美国总统艾森豪威尔心 脏病发作，他正是服用华法林进行抗凝治疗， 这使得华法林名声大震，口服抗凝药物的历史 也就此进入了华法林时代。 Dwight David Eisenhower 美国第34任总统 陆小曼、王庚 Edward A. Doisy and Henrik Dam received the Nobel Prize in Physiology or Medicine in 1943 for their discovery of vitamin K 华法林 Vitamin K
2018/10/27 Saturday Bradykinin Potentiating Factor,BPF r8 Sergio H.Fe 1934-2016 Teprotide替普罗肽 ,随后将其取名为“缓表肚 但是这种 期，儿分钟 发现地运精暖的作用 Ligand-based Drug Design Rational Drug Design 施责宝捡了个宝 Bristol-Myers Squibh John Robert Vane and Miguel Ondetti Cushman在《生物化学杂志》上看到Byersz和Nolfenden2发表的一篇关 子新型数肤酶A抑制剂苄基琉珀酸的文章，这篇文章使Cushman看到 ACE抑制剂研发的曙光.子是他清来Ode一块讨论。试用从活性结构 相对明确的獭基肤酶及其抑制剂中寻找交口。 6
2018/10/27 Saturday 6 1933年，刚毕业的Maurício Oscar da Rocha e Silva，曾目睹了一位被巴西蝮蛇 咬伤的患者不治而死的全过程。1948年他从蛇毒中成功提取了一个具有多肽结构的 特殊物质，并证实该多肽可导致血管扩张，随后将其取名为“缓激肽”，但是这种 物质在血液里的半衰期很短，几分钟就完全失效了，因此没有太大的实用价值。 1965年，Sérgio Henrique Ferreira (Maurício Oscar da Rocha e Silva的博士生) 发现蛇毒本身还具有增强缓激肽的作用. Bradykinin Potentiating Factor, BPF Maurício O. Rocha e Silva (1910-1983) Sérgio H. Ferreira (1934 –2016) Bradykinin 缓激肽 Teprotide 替普罗肽 Ligand-based Drug Design Cushman在《生物化学杂志》上看到Byers和Wolfenden发表的一篇关 于新型羧肽酶Ａ抑制剂苄基琥珀酸的文章，这篇文章使Cushman看到 ACE抑制剂研发的曙光，于是他请来Ondetti一块讨论，试图从活性结构 相对明确的羧基肽酶及其抑制剂中寻找突破口。 Rational Drug Design John Robert Vane Dave Cushman and Miguel Ondetti 施贵宝 捡了个宝 Bristol-Myers Squibb
2018/10/27 Saturday Lead compounds from the natural world Captopril-1999 Albert Lasker Clinical Medical Research Award Venoms and toxins 的 David Cushman and miguel ond HS. 心 OH Captopril (anti-hy pertensive) 卡托普利，DA1982 Serendipity Finding "Chance favors the prepared mind" Alexander Fleming discovered penicillin in 198 but The first real breakthrough in the field of anti-infectives was the discovery of the B-lactam antibiotics such as penicillin G.Fleming received Nobel Prize in 1945. H.W.Florey goterud Penicillin in put it into cinic use. 7
2018/10/27 Saturday 7 Lead compounds from the natural world Captopril (anti-hypertensive) Venoms and toxins David Cushman and Miguel Ondetti Captopril ---1999 Albert Lasker Clinical Medical Research Award 卡托普利, FDA 1982 74 C C O NH N S H H H COOH H H O The first real breakthrough in the field of anti-infectives was the discovery of the -lactam antibiotics such as penicillin G. Fleming received Nobel Prize in 1945. H. W. Florey got crud Penicillin in 1940 and put it into clinic use. Alexander Fleming discovered penicillin in 1928 but 1943 in clinic. Serendipity Finding “Chance favors the prepared mind
2018/10/27 Saturday Dorothy Hodgkin determined the chemical structure of penicillin 魔舞更什公紧 Synthesizing Penicillin 0-2002 在解折青塞素的结(194) 1915-99ha nade1961 into After nine years of hard work at the Massachusetts Institute of g pen 8
2018/10/27 Saturday 8 75 Dorothy Hodgkin determined the chemical structure of penicillin 牛津大学科学史博物馆中摆 放着霍奇金发现青霉素分子 结构的示意模型，黑色线圈 表示电子云，从线圈的密度 能推断出是什么原子 Molecular model of penicillin by Dorothy Hodgkin, c. 1945 76 Synthesizing Penicillin . John Clark Sheehan (1915 –1992) After nine years of hard work at the Massachusetts Institute of Technology (M.I.T.), he became the first to discover a practical method for synthesizing penicillin V in 1957. Ampicillin, a commonly used semi-synthetic penicillin that is taken orally rather than by injection, was discovered in 1958 and came into commercial use in 1961. Edward Abraham, Wilson Baker (1900-2002), Erns Chain, Robert Robinson 在解析青霉素的结（1944）
2018/10/27 Saturday Dorothy C.Hodgkin And Vitamin B12 a. “ First disclosed at a symposium in 1961 then in a publication in 1962 A Molecule You Can't Live Without It-Cholesterol and some sex hormones. 9
2018/10/27 Saturday 9 77 Dorothy C. Hodgkin And Vitamin B12 First disclosed at a symposium in 1961; then in a publication in 1962 A Molecule You Can't Live Without It-Cholesterol Cholesterol plays an essential role in the cell's functioning; it stabilizes cell membrane structures and is the biochemical "parent" of cortisone and some sex hormones
2018/10/27 Saturday Cholesterol and Cardiovascular Disease Regulation of cholesterol synthesis used on the attention to HMG-CoA s the rate- ng enzyme in the 含 Cholesterol Biosynthetic Pathway Elucidated step in bio “o holester 人人人 人人 g69 一 o6dFooraenedtcobdrhwcoea9 0
2018/10/27 Saturday 10 Cholesterol and Cardiovascular Disease 1815 isolated 1950's Biosynthetic pathway elucidated HO H H H H Feodor F. K. Lynen 1964 NP Konrad E. Bloch 1964 NP Michel E. Chevreul This finding focused on the attention to HMG-CoA reductase as the rate-controlling enzyme in the Cholesterol biosynthetic pawthway. Their studies led to the development of statin drugs Regulation of cholesterol synthesis 发现胆固醇合成的 原料—乙酰辅酶A Konrad Emil Bloch (1912-2000) Cholesterol Biosynthetic Pathway Elucidated Feodor Felix Konrad Lynen (1911-1979) Bloch and Feodor Lynen received the Nobel Prize in Physiology or Medicine in 1964 for discoveries concerning the mechanism and regulation of the cholesterol and fatty acid metabolism. Cholesterol Biosynthetic pathway elucidated in 1950. acetyl CoA + acetoacetyl CoA HMG CoA HMG CoA synthase HMG CoA reductase mevalonate mevalonate PP farnesyl PP squalene lanosterol cholesterol HO SCoA O OH O HO OH O OH HO PP O OH PP farnesylated proteins HO H H HO H H H H steroid hormones vitamin D bile acids What inhibiting the rate-limiting step in biosyn. pathway of cholesterol