One of the mechanism actions of antimalarial drugsis by an inhibiting on the enzyme dihydrofolate reductase
(DHFR), an enzyme target antifolate drug. Epi-croomine and croomine, are alkaloids isolated from
Stemonatuberosa showed DHFR inhibition with Ki of 61.14 and 100.59 μM and KM values of30.68 and 27.06 μM at
10 ppm. The IC50 to the DHFR of croomine and pyrimethamine were 5.29 and 7.71 μM, respectively.
Tuberostemonine is not active to the enzyme. The kinetic analysis showed that both epi-croomine and croomine
competitively inhibited to the human DHFR recombinant. The molecular modeling of the compounds to the human
DHFR was estimate depi-croomine and croomine’s binding free energy of -6.66 and -7.60 kcal/mol. The docking
showed that both epi-croomine and croomine could possibly form hydrogen bonds with the amino acid residue of
theAla9, which residues on the active site of the enzyme.