Design, synthesis and evaluation of the cytotoxicity of a N-mustard and paclitaxel conjugate prodrug

doi:10.5246/jcps.2013.02.018

Abstract

Abstract:

The syntheses and preliminary biological evaluation of a potentially bioreductive N-mustard and paclitaxel conjugate prodrug 3 targeting hypoxic tumor tissue are described. Aromatic nitro group was used as the bio-reductive trigger. Generation of paclitaxel occurred after reduction via a subsequent mechanism of “cyclization-cyclization-extrusion”. The prodrug was stable in PBS (pH = 7.4) and released paclitaxel after chemical reduction of the nitro functionality. In aerobic cytotoxicity assays, it exhibited diminished cytotoxicity and is a candidate for further biological evaluation.

Key words: Paclitaxel, N-mustard, Prodrug, Hypoxia

CLC Number:

R916

Supporting:

Junchao Shao, Haixia Lin^*, Yongmei Cui, Shaoman Yin, Erwin G Van Meir, Jiachen Huang. Design, synthesis and evaluation of the cytotoxicity of a N-mustard and paclitaxel conjugate prodrug [J]. , DOI: 10.5246/jcps.2013.02.018.

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