An overview of quinoline as a privileged scaffold in cancer drug discovery

ABSTRACT

Introduction: The concept of privileged structures is well known and is often used in the process of drug design and development. Although its assumptions are not clear, its overall usefulness remains high. Various substructures have been identified as privileged and quinoline is a prime example of such a structure.

Areas covered: Quinoline drugs that are currently approved or under clinical investigation were reviewed based on a literature search. Their modes of action and outcomes during clinical research are discussed.

Expert opinion: Undoubtedly, quinoline-based compounds have a significant impact on anticancer drugs. Although topoisomerase and kinase inhibitors are the only two different classes of agents that are currently approved for anticancer therapy, more than twenty different drug candidates are being tested on humans. The quinoline moiety offers an easily accessible, well-understood scaffold for designing new drugs. It is also a very druggable molecule with the potency for structure optimization through established synthetic pathways. For these reasons, quinoline-based anticancer drugs have a strong position in modern medicinal chemistry.

KEYWORDS:

• Anticancer drugs
• camptothecins
• privileged structures
• quinolines
• kinase inhibitors

Article highlights

• Fragment-based design and the privileged structure (PS) approach are two alternative approaches for drug development.

• The quinoline scaffold remains one of the most frequently used in medicinal chemistry and is present in many drugs and active substances.

• The apparent effectivity and druggability of quinoline supports its status as a privileged structure.

• Quinoline is very useful scaffold for the design of anticancer drugs

• There are 25 quinoline based anticancer drugs under clinical investigation. Quinoline-based compounds have a prominent place as anticancer agents

This box summarizes key points contained in the article.

Declaration of interest

The author has 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.

Additional information

Funding

R Musiol is supported by the Polish National Center for Science with grant number 2013/09/B/NZ7/00423.