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Salts of 2,3,8,9-tetrasubstituted alkoxy-, hydroxy-, and acetoxybenzo(c)phenanthridines as well as the corresponding 6-methoxy-5,6-dihydrobenzo(c)phenanthridines were prepared from appropriate chalcones through the tetralone and the 4b,10b,11,12-tetrahydrobenzo(c)phenanthridine intermediates. Complete O-demethylation of the tetramethoxybenzophenanthridine was achieved by fusion with pyridine hydrochloride at elevated temperature. The title compounds are active against leukemias L1210 and P388 in mice and some are curative against Lewis lung carcinoma. The importance of the nature of the environment about the nitrogen atom of these compounds and the substituents is discussed. 3,4-Dimethoxy-3,4-methylenedioxychalcone possesses activity against leukemia P388.

Salts of 2,3,8,9-tetrasubstituted alkoxy-, hydroxy-, and acetoxybenzo(c)phenanthridines as well as the corresponding 6-methoxy-5,6-dihydrobenzo(c)phenanthridines were prepared from appropriate chalcones through the tetralone and the 4b,10b,11,12-tetrahydrobenzo(c)phenanthridine intermediates. Complete O-demethylation of the tetramethoxybenzophenanthridine was achieved by fusion with pyridine hydrochloride at elevated temperature. The title compounds are active against leukemias L1210 and P388 in mice and some are curative against Lewis lung carcinoma. The importance of the nature of the environment about the nitrogen atom of these compounds and the substituents is discussed. 3,4-Dimethoxy-3,4-methylenedioxychalcone possesses activity against leukemia P388.

SummaryThe growth of P388 leukemia cells as an ascites tumor is markedly depressed in mice fed a zinc-deficient diet. Tritiated-thymidine labeling data suggest that zinc-deficient tumor cells accumulate in G1.We acknowledge with thanks the expert technical assistance of Mr. J. Meneses. DHB was supported by U.S. Public Health Service Medical Student Summer Research Fellowship No. FR 05355-10. Work performed under the auspices of the U.S. Atomic Energy Commission.

AC-3579 (NSC-170561), a diazafluoranthen derivative, was given intraperitoneally (100 to 300 mg/kg per day) to BDF1 mice with P388 or L1210 leukemia from day 1 to 9 or until death. Its administration produced an increase of the survival time over the controls of 44 to 66% in P388 and 23 to 28% in L1210. A 5-day administration of the drug (100 mg/kg per day) resulted in a 3-fold decrease of the number of cells per ascites. Electron microscopic examination of cells remaining in the peritoneal cavity after the treatment failed to demonstrate any striking modification. Biochemical determination showed a 70% increase of total cellular phospholipids and a marked enhancement of [32P]-orthophosphate incorporation into total phospholipids. Specific activities of ATPase and 5′AMPase as well as the labeling index with tritiated thymidine were not affected by the treatment in vivo. Both morphologic and chemical data indicated that the antitumor action of AC-3579 could differ from its effect on rat hepatocytes which has been previously elucidated.