Comparison of methyl isoeugenol and methyl eugenol as renewable starting reagents for the synthesis of thiourea compounds for anti-Plasmodium falciparum

Several thiourea derivative compounds have been used as inhibitors of Plasmodium falciparum via the plasmepsin inhibition pathway. The thiourea derivative (compound 3) namely 1-{1-(3,4-dimethoxyphenyl)-4.6-bis[(3,4-dimethoxyphenyl)methyl]heptane-2-yl]-3-{[ (2E)-3-phenylprop-2-en-1-ylium-1-yl]amino}thiourea was synthesized using the one-pot synthesis method by comparing the renewable starting reagents Methyl Isoeugenol (MIE) and Methyl Eugenol (ME). Observation using FTIR and LCMS-MS was shown that ME is more representative as a precursor. Compound (3) was synthesized using ME isothiocyanate compound (2), hydrazine, and cinnamaldehyde at 70 °C for 5 h, yielding 0.2769 g (22.47 %), and the molecular ion is 740 (98 % area). In vitro bioactivity tests against Plasmodium falciparum 3D7 of compound (3) resulted in IC50=10.19 ppm. Molecular docking of ligand (3) gave an insight that the compound (3) was a promising anti-Plasmodium falciparum compound.