A Survey of Synthetic Routes and Antitumor Activities for Benzo[g]quinoxaline-5,10-diones

Alain G. Giuglio-Tonolo,Christophe Curti,Thierry Terme,Patrice Vanelle

doi:10.3390/molecules25245922

Abstract

Anthracycline antibiotics play an important role in cancer chemotherapy. The need to improve their therapeutic index has stimulated an ongoing search for anthracycline analogs with enhanced properties. This review aims to summarize the common synthetic approaches to benzo[g]quinoxaline-5,10-diones and their uses in heterocyclic chemistry. Because of the valuable biological activities of the 1,4-diazaanthraquinone compounds, a summary of the most promising heterocyclic quinones is provided together with their antitumor properties.

Highlights

IntroductionThe substructure of 1,4-anthraquinones (anthracene-9,10-diones) is an important class of bioactive non-heterocyclic quinonoid compounds (Figure 1)
The substructure of 1,4-anthraquinones is an important class of bioactive non-heterocyclic quinonoid compounds (Figure 1)
The 2,3-dichloro-1,4-naphthoquinone 1 is the most used substrate for the preparation of 1,4-naphthoquinone heteroannulated to a quinoxaline ring by multistep reactions synthesis (Scheme 1)

Summary

Introduction

The substructure of 1,4-anthraquinones (anthracene-9,10-diones) is an important class of bioactive non-heterocyclic quinonoid compounds (Figure 1). They include natural anthracyclines such as Daunomycin, mainly active against acute lymphoblastic leukemia and acute myeloid leukemia, and Doxorubicin approved for the treatment of a wide variety of liquid and solid tumors [1]. The reference synthetic 1,4-anthraquinone is Mitoxantrone, with anticancer applications and active on multiple sclerosis through its immunosuppressant properties [2] Both drugs have adverse side effects typical of non-selective cytotoxic drugs, with inhibitor effects on rapidly dividing tissues (hair, bone marrow and mucous membranes). 1,4-anthraquinones produce a dose-limiting specific toxicity to the heart This has led to the development of many analogs with reduced toxicity and improved spectrum of activity [3]. An aza-anthracenedione, was developed to reduce cardiotoxicity typically associated with anthracyclines but without compromising antineoplastic efficacy [4]

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Discussion

Conclusion