Synthesis and evaluation of taxol-folic acid conjugates as targeted antineoplastics.
A series of Taxol derivatives tethered at C2' and C-7 to glutamate and folate have been synthesized for evaluation as prodrugs which release Taxol via hydrolytic lability of their alpha-alkoxy and alpha-amino esters. The half-time for hydrolysis of these materials was determined in pH 7 and pH 5 buffer. The in vitro cytotoxicity has been assessed in cell culture against A-549 lung cancer, MCF-7 breast cancer, and HT-29 colon cancer. Selected agents were further screened for folate binding and competitive binding with free folic acid. One agent (54), further evaluated in animal studies was found to increase the lifespan in mice, but was less effective than Taxol itself.
Lee
Jae Wook
JW
Department of Chemistry, Purdue University, West Lafayette, IN 47907, USA.
Lu
June Y
JY
Low
P S
PS
Fuchs
P L
PL
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D004353:Drug Evaluation, Preclinical; D004354:Drug Screening Assays, Antitumor; D005492:Folic Acid / Q000737:chemistry*; D006801:Humans; D006868:Hydrolysis; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry / Q000379:methods; D017239:Paclitaxel / Q000737:chemistry*; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D005492:Folic Acid; D017239:Paclitaxel