Synthesis and biological screening of some pyridine derivatives as anti-malarial agents

Abstract

Two series of pyridine derivatives were synthesised and evaluated for their in vivo anti-malarial activity against Plasmodium berghei. The anti-malarial activity was determined in vivo by applying 4-day standard suppressive test using chloroquine (CQ)-sensitive P. berghei ANKA strain–infected mice. Compounds 2a, 2g and 2h showed inhibition of the parasite multiplication by 90, 91 and 80%, respectively, at a dose level of 50 µmol/kg. Moreover, The most active compounds (2a, 2g and 2h) were tested in vitro against CQ-resistant Plasmodium falciparum RKL9 strains where compound 2g showed promising activity with IC₅₀ = 0.0402 µM. The compounds were non-toxic at 300 and 100 mg/kg through the oral and parenteral routes, respectively. The docking pose of the most active compounds (2a, 2g and 2h) in the active site of dihydrofolate reductase enzyme revealed several hydrogen and hydrophobic interactions that contribute to the observed anti-malarial activities.

Keywords::

• Pyridine derivatives
• in vivo
• anti-malarial
• docking
• acute toxicity
• dihydrofolate reductase

Acknowledgements

The authors wish to thank the Egyptian Fund for Technical Cooperation with Africa, Ministry of Foreign Affairs, Egypt, for the financial support that enabled Prof. Adnan Bekhit and Prof. Abdel Maaboud Mohamed to be available in School of Pharmacy, Addis Ababa University.

Declaration of interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.