Terpyridines as promising antitumor agents: an overview of their discovery and development

ABSTRACT

Introduction

The fused aromatic system of terpyridines makes them good, innocent ligands for various metals. The resulting complexes have been extensively studied for both their biological activity and physico-chemical properties. However, although free ligands also have an interesting biological activity, their share in recent research is considerably limited.

Areas covered

This review covers the literature on the anticancer activity of terpyridines with special attention being paid to their use as free ligands. Whenever possible, the mechanism of action has been discussed, thereby providing evidence of the substantial differences between sole ligands or less stable complexes and those that have heavier elements.

Expert opinion

The existing literature indicates that there is a specific attitude for investigating terpyridines and their transition metal complexes. While the latter have been well explored and recognized in the scientific community, the free terpyridines are considered to be useful solely due to their complexing ability. At the same time, terpyridines could have similar or even higher anticancer potency than their complexes. Moreover, a mechanistic analysis of the stability and intracellular activity would provide information that would be useful for designing new drugs.

KEYWORDS:

• Terpyridine
• metal-based drugs
• chelators
• complexes
• anticancer
• reactive oxygen species

Article highlight box

• Metal-based drugs have attracted attention since the introduction of cisplatin

• Terpyridines are strongly chelating agents that have potential in medicinal chemistry

• Complexes of terpyridines with transition metals were evaluated as anticancer agents

• Despite intensive research, the pharmacology of pure ligands is not yet fully understood

• The different degrees of the stability of complexes, particularly those with first row transition metals, does not always enable the results to be interpreted.

• The authors postulate that every work concerning the terpyridine complexes should involve free ligands as a control probe.

Disclosure ststement

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer Disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

The authors are funded by the National Science Centre (Narodowe Centrum Nauki), Poland (grant number: 2018/31/B/NZ7/02122).