Effects of isatin N-Mannich bases on HeLa cells

A congeneric series of 5-haloisatins was synthesised and tested for biological activity. Mannich bases and hydrazones of 5-chloro- and 5-iodoisatin were prepared and their structures were determined spectrophotometrically. Morphological deformations and inhibition of radiolabelled precursor incorporation into DNA were studied in HeLa cell culture; antimitotic activity was examined using a phyto test with Lepidium sativum L. I50 values were determined for the most interesting compounds. The results obtained can be interpreted in terms of the group contributions to the parent molecule. Introduction of iodine into the aromatic moiety of isatin (position 5) considerably increased inhibitory potency of the parent molecule. Furthermore, N-bis-(2-chloroethyl) and N-bis-(2-hydroxyethyl) groups, respectively, as amino components of some of the N-Mannich bases, markedly enhance the biological activities studied in this work.