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The Effects of a Series of 9-Alkylpurines on the Growth of Sensitive and 6-MP-resistant H.Ep. #2 Cells^*

( Kettering-Meyer Laboratory, Southern Research Institute, Birmingham, Alabama)

A systematic study of the activity of 6-mercaptopurine, hypoxanthine, adenine, and 6-chloropurine substituted at the 9-position with normal alkyl and cycloalkyl groups indicates that the butyl, pentyl, cyclopentyl, hexyl, cyclohexyl, heptyl, and octyl derivatives of these purines exerted an inhibitory effect on a line of H.Ep. #2 sensitive to MP and on two sublines resistant to MP. Additionally, the data indicate that generally the MP-1 line was inhibited by the 9-alkylpurine derivatives to a greater degree than was the MP-2 line. Although both of the resistant lines were more sensitive to the short-chain normal alkyl derivatives and all the cycloalkyl derivatives than was the parent line, there was little difference in the sensitivity of all three of the cell lines to the longer-chain normal alkyl derivatives. Of the compounds tested, the most effective were the cyclohexyl derivatives, which were consistently more inhibitory against all three of the cell lines. Except for the long-chain normal alkyl purines, the derivatives of MP were more inhibitory than the corresponding alkyl derivatives of hypoxanthine, which, in turn, were more inhibitory than the corresponding derivatives of adenine and chloropurine.

^* This work was supported by the Cancer Chemotherapy National Service Center, National Cancer Institute, under the National Institutes of Health Contract No. SA-43-ph-2433, and by grants from the Charles F. Kettering Foundation and the Alfred P. Sloan Foundation.

Affiliated with the Sloan-Kettering Institute.

Received 10/ 1/61.