Evaluation of paclitaxel rearrangement involving opening of the oxetane ring and migration of acetyl and benzoyl groups.
The stability of drug is a critical factor in quality control, drug efficacy, safety, storage, and production conditions. The rearrangement of paclitaxel, which involves opening of the oxetane ring and migration of acetyl group occurred on heating a powder of purified paclitaxel. Subsequently, the unusual migration of benzoyl groups progressed rapidly in organic solvents. These rearrangement derivatives were isolated carefully. The structures of the intermediate derivative A and the product derivative B were confirmed using (1)H NMR, high performance liquid chromatography (HPLC), and mass spectrometry. We proposed the rearrangement pathway here for the first time. Neither derivative exhibited bioactivity in SKOV3 (ovarian cancer) or MDA-MB-435 (breast cancer) cell culture assays.
Pyo
Sang-Hyun
SH
Samyang Genex Food & Bio Research Center, 63-2 Hwaam-Dong, Yuseong-Gu, Daejeon 305-717, South Korea. shpyo@cnu.ac.kr
Cho
Jin-Suk
JS
Choi
Ho-Joon
HJ
Han
Byung-Hee
BH
D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry* / Q000494:pharmacology; D045744:Cell Line, Tumor; D002851:Chromatography, High Pressure Liquid; D005260:Female; D006801:Humans; D007202:Indicators and Reagents; D007624:KB Cells; D009682:Magnetic Resonance Spectroscopy; D017239:Paclitaxel / Q000031:analogs & derivatives* / Q000737:chemistry* / Q000494:pharmacology; D013778:Tetrazolium Salts; D013844:Thiazoles
D000972:Antineoplastic Agents, Phytogenic; D007202:Indicators and Reagents; D013778:Tetrazolium Salts; D013844:Thiazoles; C022616:thiazolyl blue; D017239:Paclitaxel