Ellipticin cytotoxic activity

The effects of amine-substituted ellipticine derivatives 88 and 105-111 on L1210 and the human colon tumor (HCT8) in vitro (Table III) indicate that these compounds are not more cytotoxic than ellipticine (1) (71). Furthermore, only a low order of activity was revealed in vivo against P388 for 110 and 111. The N-6 derivatives were inactive as antitumor agents. However, the DNA binding properties of all of these amine-substituted ellipticines were superior to 1, as determined by the ethidium displacement assay. 

Several ellipticines and 7//-pyrido[4,3-c]carbazoles were examined for their effect on topoisomerase I and II from trypanosomes (Table VI) (163). The activity of 9-bromoellipticine on topoisomerase II is especially interesting since it is not a DNA intercalator. Several other bis-7//-pyrido[4,3-c]carbazoles were strongly active in this assay. As indicated in Table VII, a study of the cytotoxicity and uptake by TBL CL2 mouse sarcoma cells of several oxazolopyridocarbazoles... 

The cytotoxicity of several benzo-annulated iso-a-carbolines (369-372, 377, 378, 380) has been studied in vitro on human tumor KB cells (Table X) 136). The linear ellipticine analog 371 is 10 times more active than ellipticine (1) in this screen. As was mentioned earlier, this derivative also displays significant in vivo activity against P388, L1210, and B16 implanted mouse tumors TIC values 190, 175, and 224%, respectively). The resemblance of the imine grouping of these iso-a-carbolines to ellipticine quinone imine 6 is obvious. It will be of interest to see how the electrophilic behavior of these compounds compares to that of the quinone imines. 

Ellipticine (E) 1 is an indolic alkaloid with antitumor activity. Some of its phenolic derivatives as N-methyl-9-hydroxyellipticine (Celiptinium), obtained from 9-hydroxy ellipticine (9-OH E), exhibit high cytotoxicity. 38 Syntheses of 9-OH E are not satisfactory considering yields and cost, justifying the attempts at the direct conversion of E to 9-OH E via 9-oxoellipticine (9-0X0 E). Potassium nitrosodisulfonate (Fremy s salt), a valuable oxidant for the synthesis of quinone-imine from heterocyclic amines,139 was used. Under these conditions the conversion of E to 9-0X0 E was observed for the first time. Its reduction to 9-OH E is then easily achieved with ascorbic acid. The radical nature of Fremy s salt [ 0-N(S03K)2] led us to carry out the oxidation reaction under sonication in order to increase the yields via an easier electron transfer.1 1... 

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