INHIBITION OF MULTIPLICATION 217 



1. Selectivity of Benzimidazoles 



Quantitative estimation of the toxicity of compounds for host tissue or 

 cells in vitro, through observation of macroscopic changes, reduced oxygen 

 consumption, or microscopic abnormalities, provides a means for relating 

 toxicity to inhibitory activity (Tamm, 1956b; Tamm and Nemes, 1957). The 

 relation between the two activities has been referred to as selectivity (Tamm, 

 1955). 



Marked differences have been found in the selectivity of various benzi- 

 midazole derivatives (Tamm, 1956b). With numerous compounds, toxicity 

 for the chorioallantoic membrane in vitro and inhibitory activity relative to 

 influenza virus multiplication vary independently. With chloro-ribofurano- 

 syl derivatives, chloro substituents in the benzenoid ring increased inhibitory 

 activity considerably more than toxicity. 



Toxicity for monkey kidney cells in vitro and inhibitory activity against 

 poliovirus multiplication show different relationships (Tamm and Nemes, 

 1957). The a-linked arabinopyranoside (DAB) was the most selective com- 

 pound studied; ^-linked ribofuranosides were no more selective than unsub- 

 stituted benzimidazole in this system. 



B. Amino Acids and Derivatives 



A number of natural amino acids and a variety of derivatives have been 

 found to inhibit the multiplication of various animal viruses (Matthews and 

 Smith, 1955; Hurst and Hull, 1956; Tamm, 1958). In relation to the mechanism 

 of inhibitory activity, consideration of the derivatives appears to be more 

 fruitful than discussion of results secured with the natural compounds. 



/3-2-Tkienylalanine inhibits the multiplication of vaccinia virus in chick 

 embryo tissue in vitro (Thompson and Wilkin, 1948) and poliovirus, type 2, in 

 tissue culture (Brown, 1952). In both instances, phenylalanine counteracted 

 the inhibitory effect. 



DL-Methoxinine inhibits the multiplication of vaccinia virus in tissue 

 culture (Thompson, 1947) and influenza A virus in the chorioallantoic 

 membrane in vitro (Ackermann, 1951a). In the latter instance, L-methionine, 

 but not D-methionine, annulled the inhibitory effect. At inhibitory concentra- 

 tion the compound did not affect the respiration of the membrane. As 

 indicated hi a preceding section, some function of methionine rather than its 

 synthesis is inhibited by the analog (Ackermann, 1951a) and this function is 

 completed before infective virus particles appear (Ackermann and Maassab, 

 1954b). 



DL-Ethionine inhibits the multiplication of poliovirus, type 2, in brain 

 tissue in vitro (Brown and Ackermann, 1951), and influenza virus in the 

 chorioallantoic membrane in vitro (Ackermann, 1951a). In both instances, 

 the inhibitory effect was prevented by methionine. 



