Zhou Tao, Neubert Hendrik, Liu Ding Yong, Liu Zu Dong, Ma Yong Min, Kong Xiao Le, Luo Wei, Mark Sykes, Hider Robert C
Department of Pharmacy and Drug Control Centre, King's College London, Franklin-Wilkins Building, 150 Stamford Street, London SE1 9NH, UK.
J Med Chem. 2006 Jul 13;49(14):4171-82. doi: 10.1021/jm0600949.
A range of iron binding dendrimers terminated with hexadentate ligands formed from hydroxypyridinone, hydroxypyranone, and catechol moieties have been synthesized in order to investigate their potential as clinically useful iron(III)-selective chelators capable of removing dietary iron from the gastrointestinal tract and preventing the development of iron overload typical of haemochromatosis and thalassaemia intermedia. The iron chelating abilities of these molecules have been characterized by MALDI-TOF mass spectrometry and UV spectrometry. Hydroxypyridinone-terminated dendrimers were found to possess a high affinity and selectivity for iron(III). A hydroxypyridinone-based dendrimer was demonstrated to be highly efficient at reducing the absorption of iron(III) in rat intestine. This family of dendrimers may find an application in the treatment of iron overload.
为了研究一系列由羟基吡啶酮、羟基吡喃酮和儿茶酚部分形成的以六齿配体为末端的铁结合树枝状大分子作为临床上有用的铁（III）选择性螯合剂的潜力，这些螯合剂能够从胃肠道中去除膳食铁，并预防血色素沉着症和中间型地中海贫血典型的铁过载的发展。这些分子的铁螯合能力已通过基质辅助激光解吸电离飞行时间质谱（MALDI-TOF质谱）和紫外光谱进行了表征。发现以羟基吡啶酮为末端的树枝状大分子对铁（III）具有高亲和力和选择性。一种基于羟基吡啶酮的树枝状大分子被证明在降低大鼠肠道中铁（III）的吸收方面非常有效。这一系列树枝状大分子可能在铁过载的治疗中找到应用。
