62 



SECTIONAL ADDRESSES 



methods employed by Laidlaw, Dobell and Bishop, none of these sub- 

 stances prevented the growth of Entamoeba histolytica in culture at a 

 dilution of i in 5,000, whereas the control substance, emetine, was effective 

 at a dilution of i in 500,000. For the purpose of testing a further series 

 of woquinoline derivatives, prepared by Child and Pyman (193 1), the 

 method of Laidlaw, Dobell and Bishop was used in our own bacterio- 

 logical department by Mr. Couhhard with the help of strains kindly given 

 to us by Dr. Dobell. This further series was designed to find out 

 whether the reduced benzpyridocoline ring (which is a feature of Brindley 

 and Pyman's formula for emetine), or other systems in which the tertiary 

 nitrogen atom of emetine is common to two rings conferred amcebicidal 

 properties or not. This group of compounds, which included 10: 11- 

 dimethoxy-i : 2 : 3 : 4 : 6 : 7-hexahydrobenzpyridocoline (III), proved to 

 be but feebly active compared with emetine, for the most highly amcebi- 

 cidal member of the series 9 : io-dimethoxy-3-phenyl-5 : 6-dihydro- 

 benzglyoxalocoline (IV) only prevented the growth of Entamoeba histoly- 

 tica in cultures at a dilution of i in 25,000, whereas the control substance, 

 emetine, was effective in a dilution of i in 500,000. 



CH3O 



CH3O 



CH, 



HoC CHo 



CH CH, 



N 



CH, 



CH, 



(HI) 



CH3O 



CH.OK^y^y 



CH, 



(IV) 



The fact that we had now suitable strains and a technique for carrying 

 out amcebicidal tests in vitro led us to test a series of compounds, originally 

 prepared for another purpose, with interesting results. 



This investigation had its origin in Gunn and Marshall's (1920) dis- 

 covery, that harmine and harmaline had some therapeutic action in malaria. 

 Further clinical trials of these compounds, however, failed to establish 

 their practical worth as antimalarial agents. Since harmine and harmaline 

 are readily accessible in quantity by extraction from Peganum harmala, 

 and their chemical constitution has features in common with those of 

 known antimalarial agents such as quinine and plasmoquin, we thought it 

 of interest to prepare a number of derivatives of these alkaloids in order 

 that they might be tested for antimalarial action. Our attention had 

 previously been focused on studies of homologous series in the course 

 of the work on 4-M-amyl-w-cresol to which I referred earlier. This 

 suggested to us that perhaps replacement of the methoxy-group of harmine 

 or harmaline by higher alkyloxy-groups might yield substances of in- 



