Nitrogen-Containing Carcinogenic Compounds

Of all the heterocyclic nitrogen compounds studied, up to the present, none has been related to the carcinogenic hydrocarbons, such as methylcholanthrene, to the extent of containing an anthracene or phenanthrene nucleus. In view of the pronounced carcinogenic action of these hydrocarbons and in view of the fact that certain nitrogen compounds not related to these hydrocarbons have been found to be carcinogenic it seemed advisable to study the carcinogenic effect of heterocyclic nitrogen compounds related to these hydrocarbons to the extent of containing an anthracene or phenanthrene nucleus. Further, since certain indole derivatives which are not related to the carcinogenic hydrocarbons have been shown to be carcinogenic it seemed of interest to prepare an indole derivative which would be related to a carcinogenic hydrocarbon and to test its carcinogenic activity. For this purpose 2,9(N)-indoloanthone was prepared. This compound is readily reduced to the anthranol which is then analogous to a hydroxybenzpyrene. However the reduced form could not be obtained pure due to the rapid oxidation by atmospheric oxygen. Therefore the oxidized form of the compound was used in the hope that this might be reduced by the body tissues.

The other heterocyclic compounds studied were 1,2(N)-pyridinoanthracene, 1,2(N)-pyridinoanthracene methiodide, 3(N), 4-pyridinophenanthrene, and 3(N), 4-pyridinophenanthrene methiodide.

In addition it was decided to test 3-aminophenanthrene. This was done because of the observation made by Shear 1 that 2-aminoan-thracene was capable of producing liver tumors and it was felt that 3-aminophenanthrene should be more effective than the corresponding anthracene derivative because, in general, phenanthrene derivatives are more efficient than anthracene derivatives.

2,9(N)-indoloanthrone was prepared by the method of Scholl. 2 Naphthalene was condensed with phthalic anhydride in the presence of aluminum chloride. Ring closure was effected by means of concentrated sulphuric acid and the resulting benzanthraquinone nitrated with a mixture of acetic anhydride and fuming nitric acid.