Evaluation of antiproliferative effect of N-(alkyladamantyl)phthalimides in vitro.

A series of (1-adamantyl)phthalimides, 1-4, and (2-adamantyl)phthalimides, 5-8, characterized by different chain length between the adamantyl and the phthalimide moiety were synthesized, as well as 1- and 2-adamantylphthalimides substituted by nitro 9, 10, and amino group 11, 12, and phthalimides bearing homoadamantyl 13 and protoadamantyl substituent 14 and 15. The compounds were tested for antiproliferative activity in vitro on a series of five human cancer lines: MCF-7 (breast carcinoma), SW 620 (colon carcinoma), HCT 116 (colon carcinoma), MOLT-4 (acute lymphoblastic leukemia), H 460 (lung carcinoma), and a non-tumor cell line HaCaT (human keratinocytes). All compounds except nitro derivatives 9 and 10 exhibited antiproliferative activity. The activity was generally better in the 2-adamantyl series 5-8 and in the compounds having the longest alkyl spacers as in 4 and 8, or with an amino group as in 9 and 10. The most active compounds with the propylene spacer 4 and 8 showed the highest selectivity toward tumor cells. The activity was found to be due to a delay in the progress through the cell cycle at G1/S phase.