Journey of anthraquinones as anticancer agents - a systematic review of recent literature

Abstract

Anthraquinones are privileged chemical scaffolds that have been used for centuries in various therapeutic applications. The anthraquinone moiety forms the core of various anticancer agents. However, the emergence of drug-resistant cancers warrants the development of new anticancer agents. The research endeavours towards new anthraquinone-based compounds are increasing rapidly in recent years. They are used as a core chemical template to achieve structural modifications, resulting in the development of new anthraquinone-based compounds as promising anticancer agents. Mechanistically, most of the anthraquinone-based compounds inhibit cancer progression by targeting essential cellular proteins. Herein, we review new anthraquinone analogues that have been developed in recent years as anticancer agents. This includes a systematic review of the recent literature (2005-2021) on anthraquinone-based compounds in cell-based models and key target proteins such as kinases, topoisomerases, telomerases, matrix metalloproteinases and G-quadruplexes involved in the viability of cancer cells. In addition to this, the developments in PEG-based delivery of anthraquinones and the toxicity aspects of anthraquinone derivatives are also discussed. The review dispenses a compact background knowledge to understanding anthraquinones for future research on the expansion of anticancer therapeutics.

Fig. 1. Milestones in anthraquinone journey as an anticancer agent.

Fig. 2. Naturally occurring anthraquinone molecules from different sources.

Fig. 3. FDA approved drugs containing anthraquinone nucleus.

Fig. 4. Structures of anthraquinone derivatives reported in the year 2005–2006.

Fig. 5. Structures of anthraquinone analogs reported in the year 2007–2012.

Fig. 6. Structures of anthraquinone derivatives reported in the year 2013.

Fig. 7. Structures of anthraquinone derivatives reported in the year of 2014.

Fig. 8. Structures of anthraquinone derivatives reported in the year 2015–2017.

Fig. 9. Structures of anthraquinone analogs reported in the year 2019.

Fig. 10. Structures of anthraquinone derivatives reported in the year 2020–2021.

Fig. 11. Anthraquinone derivatives effect the activity of topoisomerases.

Fig. 12. Structures of anthraquinone derivatives that target telomerases.

Fig. 13. Anthraquinone derivatives targeting kinases involved in cancer progression.

Fig. 14. Anthraquinone derivatives that target other miscellaneous proteins involved in cancer growth.

M. Shaheer Malik

Saleh A. Ahmed