BQ-AurIPr: a Redox-active Anticancer Au(i) Complex That Induces Immunogenic Cell Death

Overview

Journal Chem Sci

Publisher Royal Society of Chemistry

Specialty Chemistry

Date 2022 Nov 2

PMID 36320699

Authors

Ravindra D Mule

Akhilesh Kumar

Shashank P Sancheti

B Senthilkumar

Himanshu Kumar

Nitin T Patil

Affiliations

Soon will be listed here.

Abstract

Immunogenic Cell Death (ICD) is a unique cell death mechanism that kills cancer cells while rejuvenating the anticancer immunosurveillance, thereby benefiting the clinical outcomes of various immuno-chemotherapeutic regimens. Herein, we report development of a library of benzo[]quinolizinium-based Au(i) complexes through an intramolecular amino-auration reaction of pyridino-alkynes. We tested 40 candidates and successfully identified BQ-AurIPr as a novel redox-active Au(i) complex with potent anticancer properties. BQ-AurIPr efficiently triggered generation of DAMPs - the hallmarks of ICD - and was superior in terms of efficiency compared to FDA-approved drugs known to induce ICD. BQ-AurIPr significantly increased immunogenicity of cancer cells enhancing their phagocytosis when co-cultured with immune cells. Our investigation reveals that BQ-AurIPr induces oxidative stress inside mitochondria leading to mitophagy, as the mechanism for immunogenic cell death in A549 cells.

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