STRUCTURAL AND CHEMICAL ARCHITECTURE OF HOST CELLS 



119 



structures of the above-mentioned compounds are given in formula 

 (VI). 



OH 



Thymine 

 OH- 



X 



CH3 



H 



NH, 



OH 



N^\-H 



ON 

 Uracil 

 OH 



nA-f 



OH 



Br 



O-^^N 



S-bromouracIl 

 OH 



O" -^N' 



S-aminouracil 5-fluorouraci| 2-thiouracil 



NHCH 



N- methylamino 

 purine 



HC-O-C-NH, 



I II 



CH3 O 



Urethane 



NHz^N^^N H'^N' 



H 



NH, 



H'^N 



\ 



/ 



N 

 H 



Guanine 



8-CizaguanIne 



Adenine 



8— azaadenine 



(VI) 



The fohc acid antagonist, Amethopterin, is considered to inhibit thymine 

 synthesis to a greater extent than the synthesis of purines. In the presence 

 of this compound, Bahs and Dancis (1955) have observed that leukemic 

 animals effect an apparently greater synthesis of DNA purine than of thy- 

 mine. As in the case wnth aminouracil in E. coli, it appears possible to 

 synthesize a thymine-deficient DNA, and it seems reasonable to relate the 

 antitumor activity of Amethopterin to its antithymine activity. 



5-Fluorouracil and some derivatives have recently been described. The free 

 base and nucleosides appear to be very potent antitumor and antibacterial 

 agents and, in the latter, effects are inhibited by the presence of thymine or 

 its deoxyriboside (Heidelberger et al., 1957). These fluoro compounds will 

 provoke thymine deficiency and thymineless death in nonauxotrophic strains 

 of E. coli (Cohen and Earner, unpublished data). The fluorouracil deoxy- 

 riboside is converted to the deox}Tibotide by E. coli strain 15^" and tliis 

 compound is a very potent inhibitor of the enzymatic conversion of deoxy- 

 uridylic acid to thymidylic acid (Cohen, Flaks, and Earner, unpublished data). 



Unlike chlorouracil, fluorouracil will not enter DNA (Heidelberger et al., 

 1957). However, hke chlorouracil, which is capable of entering RNA, fluoro- 

 uracil also enters this type of nucleic acid. It may be asked now whether 

 these types of RNA are pathological. 



