Jr. Dimmock et al., MANNICH-BASES OF PHENOLIC AZOBENZENES POSSESSING CYTOTOXIC ACTIVITY, European journal of medicinal chemistry, 32(7-8), 1997, pp. 583-594
A number of arylazophenols 1 were converted into the corresponding mon
o Mannich bases 2 from which two quaternary salts 3a,b and an ester 3c
were prepared, A series of bis Mannich bases 4 were also synthesized.
The angles (theta) made between one of the aryl rings and the adjacen
t ate linkage were determined by electronic absorption spectroscopy. X
-ray crystallographic data were obtained for some of the Mannich bases
. The compounds were evaluated against murine P388 D1 and L1210 cells
and two human T-lymphocyte (Molt 4, GEM) lines, and most of the deriva
tives were also screened against a panel of human tumour cell lines. A
number of correlations were noted between cytotoxicity and various ph
ysicochemical constants as well as some structural features determined
by X-ray crystallography. Several of the Mannich bases were shown to
have mutagenic properties using the lambda RK mutatest; the compounds
in series 2 and 4 have the ability to penetrate the central nervous sy
stem, as revealed by their anticonvulsant properties. While series 2-4
have the potential to deaminate forming ortho quinone methides which
would be capable of alkylating cellular thiols, the results of stabili
ty studies suggest that the bioactivities noted were due to the molecu
les per se.