CHEMOTHERAPY 151 



Those Species of bacteria, yeasts and fungi which 

 require aneurin for their maximum growth are inhibited 

 ^y pyi'ithiamine, the pyridine analogue of aneurin, 



jT QTT CH3 CHj.CHaOH 



II II J '-^ 



CH3.G C— CH2— Nf ^ 



I I I ^=='^ 



N=C.NH2 Br 



whilst other organisms are not inhibited. The inhibition 

 is overcome by the addition of aneurin. The more 

 exacting a species is in its requirement for aneurin the 

 more readily is it inhibited by pyrithiamine. The ratio 

 of pyrithiamine to aneurin is about 700 for Staph, aureus 

 and 20,000 for Esch. coli. Species requiring intact 

 aneurin are much more sensitive than those requiring 

 only the pyrimidine moiety or those requiring both the 

 pyrimidine and thiazole portions of the aneurin molecule. 

 The organisms which are not affected by pyrithiamine 

 do not synthesise increased amounts of aneurin in its 

 presence in the same way that sulphonamide resistant 

 organisms synthesise greater quantities of ^^-aminobenzoic 

 acid. By growing the yeast, Endomyces vernalis, in the 

 presence of small amounts of pyrithiamine a strain 

 resistant to 25 times the normally inhibitory concentra- 

 tion has been developed. It still required aneurin, or its 

 p^Timidine moiety, as a gro\^i;h factor but, in their 

 absence, was capable of converting pyi-ithiamine into the 

 P3T:'imidine part of the anenrin molecule. 



The respiration of Plasmodia species causing malaria 

 is stopped by the inhibitory action of quinine, plasmoquin, 

 or atebrine on the hydrogenase and cytochrome oxidase 

 systems involved. 



Drug Resistant Strains. — During the investigation of 

 chemotherapy it very soon became apparent that micro- 

 organisms developed resistance to drugs. In fact most 

 organisms which have survived treatment by a drug 

 became resistant to its action. Thus Ehrlich showed 



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