B— CHEMISTRY 



63 



creased antimalarial action and the homologous series of normal alkyl- 

 harmols from methylharmol (harmine) up to dodecylharmol was prepared. 



CH3O 



N 



NH CH, 



Through the courtesy of the Chemotherapy Committee of the Medical 

 Research Council, some members of the series — for example, O-n-butyl- 

 harmol and 0-w-heptylharmol — were tested for activity against bird-malaria 

 under the direction of Prof. Keilin, of the Molteno Institute, Cambridge, 

 but were found to be inactive. 



The possibility that some members of these series might have other 

 chemotherapeutic uses was then examined, and it was found that both 

 bactericidal and amoebicidal activity increased, on ascending the homo- 

 logous series, up to a point and then started to fall. Peaks of bactericidal 

 activity were reached at butyl for B. typhosus and at amyl for S. aureus, 

 whilst the peak of amoebicidal activity was reached at 0-w-nonylharmol. 



R.W. Coefficients. Minimum concentration lethal 



to Entamoeba histolytica. 

 I in 40,000 to I in 80,000 



I in 80,000 



I in 80,000 to I in 120,000 



I in 20,000 to I in 80,000 



I in 100,000 to I in 200,000 



I in 100,000 to I in 200,000 



I in 200,000 



I in 200,000 to I in 300,000 



I in 200,000 to I in 500,000 



I in 100,000 



I in 100,000 not lethal 



The salts of this and other high members of the series were very sparingly 

 soluble in water, and consequently a further series of compounds was 

 prepared, with the hope of obtaining more readily soluble compounds. 



The method adopted was to add a further salt-forming group to the 

 molecule in the form of a terminal dialkylamino-group, such as is employed 

 in the antimalarials, plasmoquin (VI) and atebrin (VII). 



CH3CH.CH2.CH2.CH2.N(C2H5)2 CH3.CH.CH2.CH2.CH2.N(C2H5)2 



NH 



NH 



CH3O 



CaH.O 



