Phenylpropanoid conjugated iridoids with anti-malarial activity from the leaves of Morinda morindoides

Two phenylpropanoid-conjugated iridoids, deglucosyl gaertneroside ( 1 ) and morindoidin ( 2 ), were isolated from the leaves of Morinda morindoides (Rubiaceae) by activity-guided fractionation using an anti-malarial activity assay. The known related iridoids molucidin ( 3 ) and prismatomerin ( 4 ), two lignans, abscisic acid, two megastigmanes, and two flavonol glycosides were also identified. The structures of isolated compounds were elucidated using spectroscopic analysis. The isolated compounds were evaluated for anti-malarial activity against the chloroquine/mefloquine-sensitive strains of Plasmodium falciparum together with cytotoxicity against adult mouse brain cells. Potent anti-malarial activity of 3 and 4 (IC 50 of 0.96 and 0.80 μM, CC 50 of 1.02 and 0.88 μM, and SI of 1.06 and 1.10, respectively) was shown, while new iridoids 1 and 2 and pinoresinol ( 5 ) displayed moderate activity (IC 50 of 40.9, 20.6, and 24.2 μM) without cytotoxicity (CC 50 > 50 μM). These results indicate that 1 – 5 may be promising lead compounds for anti-malarial drugs. In addition, our results imply the necessity of the quality control of the extract of M. morindoides leaves based on the contents of 1 – 5 in terms of the safety and efficacy.