Newer series of trioxane derivatives as potent antimalarial agents
Among synthesized 1,2,4-trioxane derivatives, six compounds were found to be considerably potent, with better activity against resistant strain of P. falciparum than the sensitive strain. The IC50 values of the best compound with 4-hydroxyphenyl substitution were found to be 0.391 and 0.837 µg/mL against sensitive and resistant strain of P. falciparum, respectively. Results of the tested compounds were comparable with that of the standard drug, chloroquine (IC50 = 0.044 and 0.205 µg/mL against sensitive and resistant strain of P. falciparum, respectively). Docking simulation, in silico drug-likeness and ADMET studies further validated the results of in vitro antimalarial activity. Trioxane derivatives exhibited good binding affinity for the P. falciparum cysteine protease falcipain 2 receptor (PDB id: 3BPF) with well defined drug-like and pharmacokinetic properties based on Lipinski’s rule of five with additional physicochemical and ADMET parameters. In view of having antimalarial potential, newly reported 1,2,4-trioxane derivative(s) may be useful as novel antimalarial lead(s) in the discovery and development of future antimalarial drug candidates as P. falciparum falcipain 2 inhibitors against resistant malaria.
KeywordsP. falciparum Resistance 1,2,4-Trioxane Falcipain 2 inhibitors Antimalarial
Authors are thankful to Bioinformatics Infrastructure Facility, Center for Biotechnology and Bioinformatics, Dibrugarh University, Dibrugarh, Assam (India) for carrying out in silico studies. Authors are also thankful to SAIF, Panjab University, Chandigarh for providing spectral data of synthesized compounds.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no competing interests.
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