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Synthesis and In vitro cytotoxicity of poly(ethylene glycol)–epothilone B conjugates
Author(s) -
Zhang Haiyan,
Wang Kun,
Cheng Xiaochen,
Lu Yuxin,
Zhang Qinglin
Publication year - 2014
Publication title -
journal of applied polymer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.575
H-Index - 166
eISSN - 1097-4628
pISSN - 0021-8995
DOI - 10.1002/app.41123
Subject(s) - conjugate , carbodiimide , ethylene glycol , pegylation , chemistry , peg ratio , cytotoxicity , nuclear chemistry , stereochemistry , in vitro , chromatography , polyethylene glycol , polymer chemistry , organic chemistry , biochemistry , mathematical analysis , finance , economics , mathematics
Natural epothilone B (EPOB) is currently in clinical trials for treatment of advanced cancers. In this study, two poly(ethylene glycol) (PEG)–EPOB conjugates were synthesized with carbodiimide chemistry with linear PEG Methoxy‐PEG‐Carboxymethy(mPEG‐COOH) with different molecular weights (5 and 20 kDa). The products were confirmed by matrix‐assisted laser desorption/ionization time‐of‐flight mass spectroscopy and 1 H‐NMR, which showed that PEGylation only took place at the 7‐OH site of EPOB. The solubilities of PEG5K–EPOB the conjugate of mPEG‐COOH (MW 5,000) and epothilone B and PEG20K–EPOB the conjugate of mPEG‐COOH (MW 20,000) and epothilone B were determined to be 4.93 × 10 −2 and 1.58 × 10 −2 mmol/mL; this showed improvements of 35 and 11 times, respectively, over that of free EPOB (1.4 × 10 −3 mmol/mL). Moreover, the conjugates were more stable than that of free EPOB in plasma. The cytotoxicity of conjugates was evaluated on human breast cancer MCF‐7 cells with an 3‐(4,5)‐dimethylthiahiazo (‐z‐y1)‐3,5‐di‐ phenytetrazoliumromide(MTT) based assay. The half maximal inhibitory concentration of a substance(IC50) values of EPOB, PEG5K–EPOB, and PEG20K–EPOB were 6.0 × 10 −4 , 0.57, and 8.4 × 10 −3 μ M, respectively. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014 , 131 , 41123.