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

verfasst von

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

Abstract

A combination of mutasynthesis using a mutant strain of A. pretiosum 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 19 heats up in an aqueous suspension and the ansamitocin derivative 16 is released by means of a retro-Diels–Alder reaction. It exerts strong antiproliferative activity (IC₅₀=4.8 ng mg⁻¹) in mouse fibroblasts. These new types of conjugates have the potential for combating cancer through hyperthermia and chemotherapy using an electromagnetic external trigger.

Organisationseinheit(en)

Institut für Organische Chemie
Institut für Physikalische Chemie und Elektrochemie

Externe Organisation(en)

Medizinische Hochschule Hannover (MHH)

Typ

Artikel

Journal

Chemistry - a European journal

Band

23

Seiten

2265-2270

Anzahl der Seiten

6

ISSN

0947-6539

Publikationsdatum

16.02.2017

Publikationsstatus

Veröffentlicht

Peer-reviewed

Ja

ASJC Scopus Sachgebiete

Katalyse, Organische Chemie

Ziele für nachhaltige Entwicklung

SDG 3 – Gute Gesundheit und Wohlergehen

Elektronische Version(en)

https://doi.org/10.1002/chem.201604903 (Zugang: Geschlossen)