Biochemistry and chemotherapy
Biochemistry and chemotherapy
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DOI：
10.1038/151270a0
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发表时间：
1943-01-01
期刊：
影响因子：
64.8
通讯作者：
McIlwain, H
中科院分区：
文献类型：
--
作者：
McIlwain, H
化疗，从它作为一个独立的学科开始，就与当代生物化学脱节。这种分离在很大程度上是由化学治疗师维持的。第一次明确认识到酶是药物的作用部位是通过对一个过程的生理学研究，这个过程最初似乎是一种副反应，即组织中乙酰胆碱的破坏。然而，某些药物作用于酶的知识并不是开发新药的充分基础，因为生物体的大多数酶反应的性质和重要性是未知的。伍兹对磺胺和对氨基苯甲酸酯的研究可能是第一次证明化学治疗剂和结构相关的天然化合物之间的功能关系。脂肪族氨基羧酸、烟酸及其酰胺、异烟酰胺和泛酸的类似物现已被用作抗菌剂。在大多数情况下，生长受到抑制，并且可以证明抑制与结构相似的代谢物有关。在新的抑制剂中，体外实验认为泛酰牛磺酸可能在体内对溶血性链球菌具有活性。已发现泛酰牛磺酸在所示水平下在体内具有活性，其subc.注射器保护大鼠免受腹腔内感染。感染104（部分从106）倍的中期。溶血性链球菌此外，体内作用被体外预期的一定量的泛酸所取消。这是一个有限的数量。在磺胺和泛酰牛磺酸的情况下，通过生物化学方法实现的体内和体外药物作用之间的联系仅在与以前缺乏相关性相比时才令人满意。生物化学和化学疗法的相互关系还处于非常早期的阶段。所有药物的作用不是通过底物竞争。化学疗法不仅与药理学、有机化学和细菌学有关，而且与生物化学和大部分普通生物学有关，它的实际推动力有助于所有这些学科的进步。
Chemotherapy, from its initiation as a separate subject, was out of touch with contemporary biochemistry. This separation has to a large extent been maintained by chemo-therapists. The 1st clear recognition of an enzyme as the site of action of a drug came through physiol. investigations into a process which appeared at first to be a side-reaction, namely, the destruction of acetylcholine in tissues. The knowledge that some drugs act at enzymes is not, however, a sufficient basis for development of new drugs, as the nature and importance of most enzyme reactions of organisms are unknown. Woods'' work with sulfanilamide and p-amino-benzoate was probably the 1st demonstration of functional relationship between a chemotherapeutic agent and a structurally related natural compound. Analogues of aliphatic aminocarboxylic acids, of nicotinic acid and its amide, of tryptophane and of pantothenic acid have now been tested as antibacterial agents. In most cases, growth was inhibited, and the inhibitions could be shown to be related to the structurally similar metabolites. Of the new inhibitors, it was considered probable from in vitro experiments that pantoyltaurine would be active in vivo against hemolytic streptococci. Pantoyltaurine has been found active in vivo at the level indicated, its subc. injn. protecting rats from intraperit. infection with 104 (and partly from 106) times the mid. of hemolytic streptococci. Moreover, the in vivo action was annulled by an amount of pantothenate which in vitro expts. showed to be a limiting quantity. The connection which has been achieved by biochemical methods between in vivo and in vitro drug action in the cases of sulfanilamide and pantoyltaurine is satisfying only in comparison with the previous lack of correlation. The interrelation of biochemistry and chemotherapy is in its very early stages. The action of all drugs is not by substrate competition. Chemotherapy will progress best in association not only with pharmacology, organic chemistry, and bacteriology, but also with biochemistry and much of general biology, and by its practical impetus contribute to the progress of all these subjects.