Antimalarial activity of caged xanthone isolated compounds from Cratoxylum sumatranum stem bark: In vitro and in silico approaches

Preliminary research showed that Cratoxylum sumatranum extract and fractions exhibited antimalarial activity. Two caged xanthone compounds identified as cochinchinone D and cochinchinoxanthone were disengaged from an active portion of the stem bark of C. sumatranum. The purpose of this study is to determine the antimalarial activity of both compounds against Plasmodium falciparum and their in silico prediction on several food vacuole enzymes. Lactate dehydrogenase assay was used to regulate the antimalarial activity, and in silico molecular docking was carried out with a number of receptors, including plasmepsin-II, M1-alanyl aminopeptidase, and falcipain-3. Absorption, distribution, metabolism, excretion, and toxicity (ADME-T) prediction was also conducted for both compounds. The inhibitory concentration (IC 50 ) value for antimalarial activity determination was conducted by probit analysis using GraphPad Prism Version 6.0. Cochinchinone D and cochinchinoxanthone were found to have antimalarial activity, with respective IC 50 values of 4.79 µM and 4.41 µM, respectively. Cochinchinone D has a higher affinity for binding to plasmepsin-II, according to in vitro findings. Meanwhile, cochinchinoxanthone and chloroquine as standard have a better affinity to alanyl aminopeptidase. Both compounds have similar ADME-T profiles. Cochinchinone D and cochinchinoxanthone have a high antimalarial activity possibly through the mechanism of inhibition on plasmepsin-II, falcipain-3, and M1-alanyl aminopeptidase enzymes in food vacuole. Both caged compounds have the potential for further development as antimalarial.