Targeted 1,3-dipolar Cycloaddition with Acrolein for Cancer Prodrug Activation

Overview

Journal Chem Sci

Publisher Royal Society of Chemistry

Specialty Chemistry

Date 2022 Mar 28

PMID 35340932

Authors

Ambara R Pradipta

Peni Ahmadi

Kazuki Terashima

Kyohei Muguruma

Motoko Fujii

Tomoya Ichino

Satoshi Maeda

Katsunori Tanaka

Affiliations

Soon will be listed here.

Abstract

Cytotoxic anticancer drugs used in chemotherapy are often antiproliferative agents that preferentially kill rapidly growing cancer cells. Their mechanism relies mainly on the enhanced proliferation rate of cancer cells and is not genuinely selective for cancer cells. Therefore, these drugs can also significantly affect healthy cells. Prodrug therapy provides an alternative approach using a less cytotoxic form of anticancer drug. It involves the synthesis of inactive drug derivatives which are converted to an active form inside the body and, preferably, only at the site of cancerous tissues, thereby reducing adverse drug reaction (ADR) events. Herein, we demonstrate a prodrug activation strategy by utilizing the reaction between aryl azide and endogenous acrolein. Since acrolein is generally overproduced by most cancer cells, we anticipate our strategy as a starting point for further applications in mouse models with various cancers. Furthermore, cancer drugs that have had therapeutic index challenges might be reconsidered for application by utilizing our strategy.

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