No abstract

Nitrogen and sulfur mustard derivatives of a variety of quinolines, acridines, azaacridines, benzacridines, and azabenzacridines have been synthesized for studies of the roles played by their polycyclic and alkylating components in the development of antitumor and mutagenic properties. For a display of exceptionally high activity in both the bisand monoalkylating series of compounds, it appears that the polynuclear component must be an aromatic fused 3or 4-ring system connected to the mustard moiety by an aminoalkyl linkage. Such nitrogen half-mustards with an ethyl substituent on the amino nitrogen containing the 2-chloroethyl group (the ICR 170 type) display a pronounced degree of activity against ascites tumors and are highly mutagenic for Drosophila and Neurospora, but not for Salmonella. Homologs in which the ethyl group is replaced by hydrogen to give a secondary amine (the ICR 191 type) are extremely potent frameshift mutagens for Salmonella and Escherichia coli, but not for Drosophila and Neurospora, and are relatively ineffective as antitumor agents. The sulfur mustard derivatives are active against ascites tumors, but rarely display mutagenic activity. It is considered that activity is imparted to the half-mustards because of the ability of an appropriate polynuclear component to intercalate into the nucleic acids of the ascites tumors or of the bacteria accompanied by the characteristic base alkylating reaction of the 2-chloroethyl group. The ability to exert a bifunctional action is apparently a necessary requirement for both antitumor and frameshift mutagenic activity.

No abstract

The object of this investigation has been to determine the feasibility of using chemically labelled antibodies as reagents for the detection and orientation of antigenic material in mammalian tissue. Such a method requires the retention of specificity by the antibody-molecule during and after the necessary chemical manipulation, a stable chemical linkage between the antibody and its label, and a label that can be detected when present in minute quantities. A further important requirement demands the separation of the labelled-antibody solution from unconjugated tracer-material. In addition a method of this sort would obviously be more useful for many studies if it were possible to determine not only those organs, but those cells which contain the antigen in question. Accordingly we investigated the possibility of employing materials for labelling that could be detected by optical rather than by analytic or radiographic methods.

Vol. 68 tion was extracted twice more with 50-cc. portions of ether. The combined ether extracts were dried over magnesium sulfate and the ether was removed on the steam cone.Excess diamine was distilled under reduced pressure; 8.3 g. was collected at 81-82°( 14 mm.) and 5.5 g. at 45-48°( 0.5 mm.). The residue began to crystallize even before all the diamine had distilled so it was purified by recrystallization rather than by distillation. After treating with 3 g. of decolorizing charcoal in 200 cc. of boiling benzene, the benzene solution was concentrated to about 40 cc. and 300 cc. of low-boiling petroleum ether was added with stirring. The mixture was cooled and the light tan crystalline product was collected in a filter; 24.5 g. (82%), m. p. 113-119°. This product was recrystallized twice from Skellysolve B (b. p. 60-68°), yielding 20.0 g of white plates, m. p. 122-123°.