Fluorinated scaffolds for antimalarial drug discovery

ABSTRACT

Introduction

The unique physicochemical properties and chemical diversity of organofluorine compounds have remarkably contributed for their wide utility in the area of pharmaceuticals, materials and agrochemicals. The noteworthy characteristics of fluorine include high electron affinity, lipophilicity and bioavailability, extending the half-life of the drugs. The incorporation of fluorine substituents, particularly trifluoromethyl groups, into organic molecules has led to their high potency against various diseases, including malaria. Hence, organofluorinated molecules offer valuable avenues for the design of new drug candidates against malaria.

Areas covered

In this review, the authors discuss the importance of fluorine substituents present in the chemical compounds, and their potential applications for antimalarial drug discovery.

Expert opinion

Fluorinated molecules represent a reliable strategy to develop new antimalarial drugs. Fluorine or fluorinated groups have been identified as a promising precursor, and their presence in approximately twenty-five percent of approved drugs is notable. Selective fluorination of chemical entities has the potential to be applied not only to improve the activity profile against the malaria parasite, but could be extrapolated for favorable pharmacological applications. Hazardous reagents such as HF, F₂ and SF₄ used for fluorination, are not considered as safe, and therefore, this process remains challenging, particularly for the pharmaceutical industry.

KEYWORDS:

• Antimalarials
• organofluorinated
• drug Discovery
• lipophilicity
• fluorinated artemisinin

Article highlights

• Rational design of fluorinated molecules represents a reliable strategy to develop new therapeutics for the treatment of malaria disease.

• Fluorination considerably improves the activity profile, including the pharmacological features.

• The noteworthy characteristics of fluorine include high electron affinity, lipophilicity and bioavailability, extending the half-life of the drugs.

• Fluorinated analogues of approved drugs, artemisinin and mefloquine demonstrates improved activity.

• Trifluoromethyl (-CF₃) substituted compounds exhibit a notable potency against the malaria parasite.

This box summarizes key points contained in the article.

Declaration of interest

The authors have no other 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 apart from those disclosed.

Reviewer disclosures

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

Correction Statement

This article has been republished with minor changes. These changes do not impact the academic content of the article.

Additional information

Funding

The Science and Engineering Research Board, Government of India, is acknowledged for financial support [ECR/2015/000478]. The Department of Science and Technology, Government of India, is also acknowledged for the financial support (DST/TDT/AGRO-54/2019). Finally, C Upadhyay is very thankful to the Council of Scientific and Industrial Research (CSIR), New Delhi, for providing financial assistance with whom she is a Junior Research Fellow.