Ab-initio Molecular Dynamics and Density Functional Theory Study of Amodiaquine Analogues as Potential Inhibitors of β-haematin Crystallization.

Introduction: Prevention of the formation of β-haematin is the target of several existing antimalarials drugs, most notably chloroquine. This target is therefore attractive for the development of new molecules with antimalarial potential.

Method: In this study, we have used a combination of ab-initio molecular dynamics and density functional tight-binding to examine the possible interaction mechanisms between five amodiaquine analogues and four conformations of haematin. Reactivity and stability of these complexes were investigated using bond length (Fe-N and Fe-O), energies (HOMO- LUMO) and molecular dynamics.

Results: Results revealed a good interaction between haem and the compounds, stable geometries of complexes.

Conclusion: The findings from this study are valuable because they can aid the design and understanding of new therapeutic molecules that could be used to treat drug-resistant malaria, a global threat of today.