Background: Plasmodium falciparum is the most dangerous and widespread diseasecausing
species of malaria. Falcipain-2 (FP2) of Plasmodium falciparum, is a potential target for
antimalarial chemotherapy since it is involved in an essential cellular function such as hemoglobin
degradation during the parasite’s life cycle. However, despite their central role in the life cycle of
the parasite, no commercial drug targeting Falcipain-2 has been developed to date. Prior efforts to
develop peptide-based drugs against Plasmodium have been futile due to their susceptibility to being
degraded by host enzymes.
Objective: Here, we report computer-aided drug design of new nonpeptidic inhibitors against FP2,
which are likely to be safe from degradation by host enzymes.
Methods: We have virtually screened for the probable FP2 inhibitors from the PubChem database
by submitting the well-equilibrated 3-D structure of FP2. Furthermore, virtual screenings and dockings
were carried out using PyRx and Discovery Studio.
Results: We found 15 top-ranking molecules with carbaldehyde pharmacophore having a good fit
with the target protein. Based on the C-Docker values, the top 4 hits (PubChem 44138738, Pub-
Chem 20983198, PubChem 20983081 and PubChem 28951461) for FP2 were identified. These
four hits have been observed to bound to the active cleft of the protein. Moreover, their complexes
were also found to be stable from the RMSD and Radius of Gyration analysis.
Conclusion: The selected compounds 2-(benzylamino)-8-methylquinoline-3-carbaldehyde (Pub-
Chem44138738), 6-bromo-2-(3,4-dihydro-1H-isoquinolin-2-yl)quinoline-3-carbaldehyde (Pub-
Chem 20983198), 2-(3,4-dihydro-1H-isoquinolin-2-yl)-6-ethylquinoline-3-carbaldehyde(PubChem
20983081)and 2-[benzyl(methyl)amino]quinoline-3-carbaldehyde (PubChem 28951461) may be
the starting point for further modification as a new type of nonpeptidic drug for malaria disease.