In previous communications (Hurst, 1948;Hurst, Peters, and Melvin, 1950) we have recorded the therapeutic action of Nitroakridin 3582 and compared those of penicillin, chloramphenicol, aureomycin, and terramycin against psittacosis and lymphogranuloma venereum in mice or in developing chick-embryos. For the past eight years we have used these experimental infections (among others) in routine screening-tests of synthetic organic compounds for antiviral properties, and during this time have encountered a number of quite dissimilar chemical types each exhibiting some degree of activity against these particular infections. The most active compounds were quinoxaline-l: 4-dioxide and various substituted derivatives, the best of which closely approached aureomycin in therapeutic potency. Alergant (1953) has confirmed this action in human lymphogranuloma, though toxic side-reactions rule out the possibility that the compounds will be useful additions to the pharmacopoeia. The quinoxaline oxides also manifest anti-amoebic and antibacterial properties (Jones, Landquist, and Stewart, 1953; McIlwain, 1943;Francis, 1953).
METHODSThe strains of virus used, the general method of working, and the method of computing 40% endpoints (not 40% mortalities) in titrations of virus are sufficiently described in our earlier publications. When this work first began aureomycin was unknown, and in the earlier experiments we had no suitable standard of therapeutic activity. When later aureomycin became available in strictly limited quantities, we used it as a standard of reference in all experiments, giving a single dose of 1 mg. to eggs or 2 mg. twice daily to mice. Although when the antibiotic was more freely available it appeared that these were perhaps not quite the optimal doses (see Hurst, Peters, and Melvin, 1950), for the sake of consistency we decided to retain them throughout this investigation. Our experience over more than a hundred experiments, however, strongly suggests that the earliest samples of aureomycin were less effective than those issued somewhat later, so that in fact we did not achieve perfect consistency over the years, though we believe that we have done so for the greater part of the time. The largest amounts administered of other compounds were usually the "maximal tolerated doses " defined as follows: (a) for the mouse, as that quantity which, given twice daily (once on Saturday and Sunday) over a period identical with that in the chemotherapeutic test, caused no deaths and allowed the animals to attain a final weight not less than 90% of that of the controls; (b) for the egg, as that quantity which killed no embryos within five days of a single injection into the yolk-sac on the seventh day of incubation. At this point it may be noted that on many occasions we found that the maximal tolerated dose did not necessarily give results as favourable as a rather smaller one.
RESULTS
