Author/Authors :
Shu-Hui Chen، نويسنده , , Jian-Mei Wei، نويسنده , , Byron H. Long، نويسنده , , Craig A. Fairchild، نويسنده , , Joan Carboni، نويسنده , , Steven W. Mamber، نويسنده , , William C. Rose، نويسنده , , Kathy Johnston، نويسنده , , Anna M. Casazza، نويسنده , , John F. Kadow، نويسنده , , Vittorio Farina، نويسنده , , Dolatrai M. Vyas، نويسنده , , Terrence W. Doyle، نويسنده ,
Abstract :
A large number of C-4 paclitaxel analogs have been prepared in the course of our systematic C-4 modification. These include C-4 esters, carbonates, carbamates as well as a C-4 deacetyl derivative. All of these analogs were evaluated in a tubulin polymerization assay as well as in a cytotoxicity assay against a human colon cancer cell line. The potent analogs emerging from these in vitro assays were further evaluated in vivo. With the exception of paclitaxel side chain bearing C-4 carbamates and C-4 aromatic esters, most of the C-4 aliphatic esters and carbonates were found to possess comparable or superior activity to paclitaxel in vitro. Several C-4 aliphatic esters and carbonates also exhibited in vivo activities against i.p. implanted murine M-109 lung carcinoma.
