New medium oxacyclic O,N-acetals and related open analogues: biological activities.

Attention is increasingly being focussed on the cell cycle and apoptosis as potential targets for therapeutic intervention in cancer. Taking 1-[(2-oxepanyl)]-5-fluorouracil previously prepared by us, we committed ourselves to increase the lipophilicity of this upper cyclohomologue of Ftorafur and prepared a series of bioisosteric benzannelated seven-membered 5-FU O,N-acetals to test them against the MCF-7 human breast cancer cell line. Benzo-fused seven-membered O,O-acetals or their acyclic analogues led to the expected 5-FU O,N-acetals (or aminals), in addition to six- and to 14-membered aminal structures and acyclic compounds.

Growth inhibition, G(1)-arrest, and apoptosis in MCF-7 human breast cancer cells by novel highly lipophilic 5-fluorouracil derivatives.

In this study we evaluate the antitumour activity, the cell cycle arrest and apoptotic properties of novel lipophilic benzene-fused seven-membered 5-fluorouracil (5-FU) analogs in comparison to 5-FU on MCF-7 human breast cancer cells. The lipophilicities of ESB-786B, ESB-252A and ESB-928A were predicted by using the CDR option of the PALLAS 2.0 program.