1962 Volume 15 Issue 6 Pages 242-246
The antiviral effect of N′, N′-anhydrobis (β-hydroxyethyl) biguanide (ABOB)1) as evaluated in this laboratory against the PR8 strain of influenza virus both in embryonated eggs and in mice was not far different from the control. However, our later studies2) proved its effectiveness against Sendai virus in tissue culture in a reproducible manner. Meanwhile, the clinical usefulness of the compound was reported by several authors. Then the situation directed us to find more potent biguanide derivatives as anti-influenza agent. Along this line, ten biguanide derivatives were prepared. For the primary screening of these compounds, both the Sendai virus growth in HeLa cell cultures and the PR8 virus growth in the Maitland type tissue cultures of chorioallantoic membrane were used. As described above, the former system was adequately sensitive to detect the effect of ABOB and the latter has been known to be most sensitive in detecting various agents of antiviral activity, such as antimetabolites, antibodies or the inhibitors of animal origin3).
Of those compounds tested, N′-isobutylbiguanide and N′-benzylbiguanide were found more effective than ABOB at least in these tissue culture system. Moreover, toxicity test performed in mice suggested higher chemotherapeutic index of these compounds, particularly of the former. The studies to be reported in this article are chiefly concerned with the in vitro activity and the toxicity in mice of 10 compounds so far tested. The animal experiments with these in vitro effective compounds will be reported in the next paper4).
