A Bio-Chemosynthetic Approach to Superparamagnetic Iron Oxide-Ansamitocin Conjugates for Use in Magnetic Drug Targeting

作者：Wang Liang Liang; Balakrishnan Asha; Bigall Nadja Carola; Candito David; Miethe Jan Frederick; Seidel Katja; Xie Yu; Ott Michael; Kirschning Andreas

来源：Chemistry - A European Journal, 2017, 23(10): 2265-2270.

DOI：10.1002/chem.201604903

<jats:title>Abstract</jats:title><jats:p>A combination of mutasynthesis using a mutant strain of <jats:italic>A. pretiosum</jats:italic> blocked in the biosynthesis of amino‐hydroxybenzoic acid (AHBA) and semisynthesis relying on a Stille cross‐coupling step provided access to new ansamitocin derivatives of which one was attached by a thermolabile linker to nanostructured iron oxide particles. When exposed to an oscillating electromagnetic field the resulting iron oxide/ansamitocin conjugate <jats:bold>19</jats:bold> heats up in an aqueous suspension and the ansamitocin derivative <jats:bold>16</jats:bold> is released by means of a retro‐Diels–Alder reaction. It exerts strong antiproliferative activity (IC<jats:sub>50</jats:sub>=4.8 ng mg<jats:sup>−1</jats:sup>) in mouse fibroblasts. These new types of conjugates have the potential for combating cancer through hyperthermia and chemotherapy using an electromagnetic external trigger.</jats:p>

• 出版日期2017-2