Abstrak/Abstract |
Objective: To investigate in vitro antimalarial activity of chalcone derivative compounds
against Plasmodium falciparum 3D7 (Pf3D7) strain and in silico antimalarial activity.
Methods: Synthesis of the chalcone derivatives was conducted via Claisen-Schmidt
method using NaOH 60?se as catalyst. An in vitro antimalarial activity assay was
carried out according to the Rieckmann method against the chloroquine-sensitive Pf3D7
strain. Molecular docking studies of the prepared compounds were performed using
Discovery Studio 3.1 (Accelrys, Inc., San Diego, USA) software to dihydrofolate reductases–thymidylate
synthase (PfDHFR-TS) protein with Protein Data Bank ID of
1J3I.pdb (sensitive-protein) and ID: 4DP3.pdb (resistance-protein).
Results: This work has successfully synthesized seven chalcone derivatives with a great
antimalarial activity. It has been revealed that allyloxy, hydroxy and alkoxy functional
groups could increase the antimalarial activity of the chalcone derivatives. The best
antimalarial activity of the prepared compounds was possessed by 3b with an IC50 value
of 0.59 mM and categorized as an excellent antiplasmodial. Molecular docking studies of
3b showed binding interaction with the amino acid residues such as Ala16, Ile164, Phe58,
Tyr170 of the 1J3I.pdb protein and also Ala16, Phe58, Ile112, Met55 of the 4DP3.pdb
protein.
Conclusions: An in vitro antimalarial assay of the prepared chalcone derivative (3a–g)
showed an excellent and good antiplasmodial activity against the chloroquine-sensitive
Pf3D7 strain. In silico antimalarial studies revealed that 3a–g made binding interaction
with both sensitive-protein (1J3I.pdb) and resistance-protein (4DP3.pdb), which means
that they were both active against chloroquine-sensitive and resistant plasmodium strain. |