Treatment of glioblastoma multiforme cells with temozolomide-BioShuttle ligated by the inverse Diels-Alder ligation chemistry.

Drug Design, Development and Therapy
Klaus BraunWaldemar Waldeck

Abstract

Recurrent glioblastoma multiforme (GBM), insensitive against most therapeutic interventions, has low response and survival rates. Temozolomide (TMZ) was approved for second-line therapy of recurrent anaplastic astrocytoma. However, TMZ therapy in GBM patients reveals properties such as reduced tolerability and inauspicious hemogram. The solution addressed here concerning GBM therapy consolidates and uses the potential of organic and peptide chemistry with molecular medicine. We enhanced the pharmacologic potency with simultaneous reduction of unwanted adverse reactions of the highly efficient chemotherapeutic TMZ. The TMZ connection to transporter molecules (TMZ-BioShuttle) was investigated, resulting in a much higher pharmacological effect in glioma cell lines and also with reduced dose rate. From this result we can conclude that a suitable chemistry could realize the ligation of pharmacologically active, but sensitive and highly unstable pharmaceutical ingredients without functional deprivation. The TMZ-BioShuttle dramatically enhanced the potential of TMZ for the treatment of brain tumors and is an attractive drug for combination chemotherapy.

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Citations

Nov 29, 2015·European Journal of Pharmaceutics and Biopharmaceutics : Official Journal of Arbeitsgemeinschaft Für Pharmazeutische Verfahrenstechnik E.V·Manuel Gregoritza, Ferdinand P Brandl
Dec 27, 2018·Journal of Peptide Science : an Official Publication of the European Peptide Society·Mareen Pagel
Oct 10, 2014·Beilstein Journal of Organic Chemistry·Anne-Katrin SpäteValentin Wittmann
Apr 2, 2019·Beilstein Journal of Organic Chemistry·Jessica Hassenrück, Valentin Wittmann
May 1, 2021·Frontiers in Chemistry·Lisa Maria HaiberValentin Wittmann
Mar 10, 2015·ACS Applied Materials & Interfaces·Chen FangMiqin Zhang

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Methods Mentioned

BETA
FCS
flow cytometry

Software Mentioned

Cellquest
BioShuttle

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