Chloroquine-containing compounds: a patent review (2010 – 2014)

Abstract

Introduction: Chloroquine (CQ) has been well known for its antimalarial effects since World War II. However, it is gradually being phased out from clinical use against malaria due to emergence of CQ-resistant Plasmodium falciparum strains. Besides low cost and tolerability, ongoing research has revealed interesting biochemical properties of CQ that have inspired its repurposing/repositioning in the management of various infectious/noninfectious diseases. Consequently, several novel compounds and compositions based on its scaffold have been studied and patented.

Areas covered: In this review, patents describing CQ and its derivatives/compositions over the last 5 years are analyzed. The review highlights the rationale, chemical structures, biological evaluation and potential therapeutic application of CQ, its derivatives and compositions.

Expert opinion: Repurposing efforts have dominantly focused on racemic CQ with no studies exploring the effect of the (R) and (S) enantiomers, which might potentially have additional benefits in other diseases. Additionally, evaluating other similarly acting antimalarials in clinical use and structural analogs could help maximize the intrinsic value of the 4-aminoquinolines. With regard to cancer therapy, successful repurposing of CQ-containing compounds will require linking the mode of action of these antimalarials with the signaling pathways that drive cancer cell proliferation to facilitate the development of a 4-amino-7-chloroquinoline that can be used as a synergistic partner in anticancer combination chemotherapy.

Keywords:

• aminoquinoline
• antimalarial
• cancer
• chloroquine derivatives
• hydroxychloroquine
• malaria
• patent
• Plasmodium falciparum
• repositioning
• repurposing

Acknowledgements

The University of Cape Town, South African Medical Research Council, and South African Research Chairs Initiative of the Department of Science and Technology, administered through the South African National Research Foundation are gratefully acknowledged for support.

Declaration of interest

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.

Notes

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