148 OXIDATION-REDUCTION POTENTIALS 



antibiotics are successful chemotherapeutic agents and one of the most recently 

 described antibiotics, Chloromycetin, has now been synthesised and re-named 

 chloramphenicol. Apart from their great therapeutic importance antibiotic chemo- 

 therapeutic agents are interesting from the structural point of view. The living cell 

 is able to effect syntheses that tax the resources of the best equipped laboratory and 

 some of the structures produced appear quite novel to the chemist, some of the 

 moulds effecting the most versatile syntheses. The soil presents one of the richest 

 fields for discovering antibiotic-producing micro-organisms, as would be expected 

 since there must be a remarkable struggle for existence among the myriads of 

 organisms occupying the earth's crust. Those micro-organisms that have survived 

 countless ages of race- warfare might be expected to have potent weapons against 

 each other, although; perhaps unfortunately from this point of view, pathogenic 

 bacteria are relatively delicate organisms, do not generally inhabit the soil, and if 

 they did could quickly be over-grown by vigorous competitors, so that it is not often 

 that a potent antagonist can be found that is specific for human or animal pathogens. 



PENICILLIN 



Although microbial inter-antagonisms have been known for over fifty years the 

 development of penicillin has over-shadowed all previous work and opened a new 

 epoch of chemotherapy. Fleming's (1929) observation of a Penicilliu?n that produced 

 a soluble substance bactericidal to many Gram-positive bacteria was followed some 

 ten years later by the preparation of purified penicillin which is a remarkably efficient 

 therapeutic agent in many diseases (Chain, Florey, Gardner, Heatley, Jennings, 

 Orr-Ewing and Sanders, 1940). Unlike many drugs penicilHn is non-toxic, and it 

 has a number of properties that make it an ideal chemotherapeutic agent as outlined 

 earlier. The search still goes on, however, for other therapeutic agents, for penicillin 

 has the following imperfections : — 



(1) It is not effective against all micro-organisms, conspicuous failures are 

 Gram-negative bacteria, the tubercle bacilli and the viruses. 



(2) It is rapidly excreted and hence requires frequent administration 

 preferably by injection. 



(3) Organisms develop resistance to its action, and it then becomes 

 ineffective against such organisms. The mechanisms of this resistance will be 

 mentioned later. 



Several different penicillins exist and R in the following formula may represent 

 several groups, benzyl, pentenyl, etc. In connection with the mode of action of 

 penicillin the similarity of the formula to that of glutathione will be evident, but the 

 mechanism of its bactericidal action is discussed in a later section : — 



H H H V V V 



R-cT 



^ 



N— C— C-S^ CH3 



V R'-C( 



\ C-N-CHr\H3 ^O C-N-CH, 



O COOH O H COOH 



Penicillin Glutathione 



