330 Mr. C. H. Browning and others. Relationships betiveen 



Benda(l) for Ebrlich, and was named by them trypaflavin on account of its 

 powerful therapeutic properties in experimental trypanosome infections. We 

 are not aware that its action on bacteria had been investigated prior to the 

 work recorded in the above paper (2), although Shiga (10) published almost 

 simultaneously results of his investigations on its action on V. cholerce. The 

 hydrochloride and sulphate of diaminoacridine were then found to be 

 practically equal to the methochloride in antiseptic properties and in efficacy 

 of action in serum (8). In the case of these aminoacridine substances the 

 power of killing bacteria is exerted slowly ; thus, with the methochloride 

 acting on B. coli in serum, the concentration which proves lethal in 2 hours 

 (1 : 20000) is five to ten times greater than that required to produce sterility 

 after 24 hours ; on the other hand, mercuric chloride and carbolic acid pro- 

 duce their maximum effect within 2 hours, whether they be tested in a 

 solution containing a minute amount of protein (0 - 7 per cent, of Witte's 

 peptone) or in a rich protein medium such as serum. The acridine com- 

 pounds, therefore, may be said to act especially as bacteriostatic agents (7, 8). 

 This property, coupled with their relative innocuousness for mammalian 

 tissues, as tested by toxicity for the living animal as a whole (4, 7), effect on 

 phagocytosis (3, 7), and slight irritating action on the conjunctiva (7), suggested 

 that these substances should be specially applicable for the purpose of 

 restraining bacterial infections in the tissues. Thus the methochloride, 

 under the name of acriflavine, and the sulphate of diaminoacridine base, as 

 proflavine, found extensive use in the treatment of infected wounds during the 

 late war, and also in the treatment of such relatively accessible infections 

 as gonorrhoea. The present work records the investigations which have been 

 made with the view of tracing the source of the antiseptic property of 

 diaminoacridine compounds by examining substances which may be regarded 

 as fragments of the acridine molecule. The parent substance of the acridine 

 derivatives is a compound of the following formula : — 



4 9 5 

 CH CH CH 



3 HC^Y y^JCH 6 



2 ™%/%/\SCK 7 

 CH N" CH 

 1 10 8 

 Acridine. 



that is, a combination of two benzene and a pyridine ring. If the two side 

 wings are removed, a pyridine nucleus remains ; if only one wing is detached, 

 a quinoline nucleus results. It seemed, therefore, possible that the antiseptic 

 activity of acriflavine (diamino acridine methochloride) might reside either 



