PARP inhibitor cyanine dye conjugate with enhanced cytotoxic and antiproliferative activity in patient derived glioblastoma cell lines.

Bioorganic & Medicinal Chemistry Letters
Peter J ChoiJiney Jose

Abstract

We describe the synthesis and in vitro activity of drug-dye conjugate 1, which is a combination of the PARP inhibitor rucaparib and heptamethine cyanine dye IR-786. The drug-dye conjugate 1 was evaluated in three different patient-derived glioblastoma cell lines and showed strong cytotoxic activity with nanomolar potency (EC50: 128 nM), which was a 780 fold improvement over rucaparib itself. We also observe a synergistic effect of 1 with temozolomide (TMZ), the standard drug for treatment for glioblastoma even though these cell lines were resistant to TMZ treatment. We envisage such conjugates to be worth exploring for their utility in the treatment of various brain cancers.

Citations

Apr 21, 2021·Accounts of Chemical Research·Syed Muhammad Usama, Kevin Burgess
Jul 23, 2021·Chemical Society Reviews·Syed Muhammad UsamaKevin Burgess
Jul 25, 2021·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Wei WuHeike E Daldrup-Link
Jun 13, 2020·Bioconjugate Chemistry·Peter J ChoiJiney Jose
Jan 14, 2022·Nature Protocols·Thomas I-H ParkMike Dragunow

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