172 ANTIBACTERIAL SUBSTANCES FOR TREATMENT OF INFECTIONS 



Two sulphones, ^-methylsulphonylbenzamidine (CH3S02CgH4C(NH)-NH2) and p- 

 methylsulphonylbenzylamine (CH3-S02'CgH4-CH2-NH2), have a marked in vitro action 

 against Clostridia and Str. pyogenes. The former, designated V 187, has proved highly 

 effective in the treatment of experimental gas gangrene of the guinea-pig. It is not 

 antagonized to any marked extent by body fluids. The latter (V 335) is also effective 

 against gas gangrene in the guinea-pig, but is more readily antagonized by the body 

 fluids. Neither substance is antagonized by ^j-aminobenzoic acid ; and both act equally 

 well on normal and sulphonamide-resistant bacteria (Evans et al. 1944). 



Propamidine. Propamidine, 4 : 4'-diamidino-diphenoxy-propane, first proved an effec- 



NH2. ^^ -.^^ .NH2 



>C< >0-(CH2)3-0<; >C<( 



tive therapeutic agent for animal trypanosomiasis (Lourie and Yorke 1939) with a thera- 

 peutic index of about 30. It is also bacteriostatic in low concentrations, 8tr. pyogenes, 

 for example, being inhibited in dilutions of 1 : 2 x 10^, and non-toxic for leucocytes in 

 dilutions of 1 : 1,000 ; it has been used successfully in the local treatment of infections 

 of open wounds and burns (Thrower and Valentine 1943) and of conjunctivitis due to 

 the Morax-Axenfeld bacillus (Valentine and Edwards, 1944). 



It is noteworthy that propamidine bears a structural resemblance to stilbene, and 

 that a number of stilbene derivatives have a high bactericidal activity. For example, 

 deoxy diethyl stilboestrol (HO-C5H4-C(C2H5) : C(C2H5)CgH5) inhibits Str. jjyogenes in a 

 dilution of 1 : 2 x 10" (Brownlee, Copp, Duflfin and Tonkin 1943 ; see also Faulkner 1943). 

 Amino-acridine Compounds (Flavines). 



The claim of the amino-acridine compounds to chemotherapeutic rank is at present 

 not clear. Their toxicity is such that they are suitable only for application to the surface 

 of infected tissues. The degree of tissue intoxication that justifies submitting infected 

 tissues to the undoubted in vivo antibacterial action of the drugs is in dispute. Mcintosh 

 and Selbie (1942, 1943o) employed proflavine successfully in conjunction with the sulphona- 

 mides in the treatment of experimental gas gangrene. For a fuU discussion of these drugs 

 from the chemotherapeutic point of view, the reader is referred to the review of Browning 

 (1943). 



NATURAL ANTIBACTERIAL SUBSTANCES FROM 

 MICRO-ORGANISMS 



Since the early days of bacteriology and mycology, the inhibition of growth 

 of one micro-organism by the growth of another has been a familiar phenomenon, 

 and its possible significance in the therapy of infectious diseases commented upon. 

 The application of these natural bactericidal or bacteriostatic substances to the 

 treatment of infections was usually limited by the low therapeutic index of the 

 materials available ; the doses tolerated by the animal were ineffective against 

 the infecting organism. In recent years, however, improvements in methods of 

 isolation, and a clearer understanding of the antibacterial effects, have led to the 

 description of a large number of antibacterial substances from bacteria and moulds, 

 some of which are therapeutically active in experimental infection, and one at 

 least, penicillin, which is highly effective in the treatment of infective disease 

 in the human subject. 



The reader is referred to the comprehensive reviews of Porter and Carter (1938) 

 and of Waksman (1941) for a discussion of antagonisms between micro-organisms 

 and of the earlier work on natural antibacterial substances, which is beyond the 



