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

Abstract

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 avonol glycosides were also identi ed. The structures of isolated compounds were elucidated using spectroscopic analysis. The isolated compounds were evaluated for anti-malarial activity against the chloroquine/me oquine-sensitive strains of Plasmodium falciparum together with cytotoxicity against adult mouse brain cells. Potent anti-malarial activity of and 4 (IC 50 of 0.96 and 0.80 µM, 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, respectively). These results indicate that 1-5 may be promising lead compounds for anti-malarial drugs and that extracts of M. morindoides leaves could be effective remedies for malaria infection.

Phenylpropanoid-conjugated iridoid glucosides from leaves of Morinda morindoides

“…( 2) 1). The 1 H and 13 C NMR spectral data of 1 were similar to those of acetylgaertneroside (3) [3], indicating 1 to be a phenylpropanoid-conjugated iridoid glucoside. The presence of an acetyl group at C-6″ of glucose unit was indicated by the downfield-shifted chemical shift value of this position (δ H 4.22 (2H)/δ C 64.7).…”

“…To evaluate the effects of isolated compounds on parasite level of P. falciparum, a SYBR Green-based microfluorometric assay system was used as described previously [13,19,20]. Cytotoxicity of the compounds to AMB cells was evaluated as described previously [19].…”

“…As a result, the three phenylpropanoid-conjugated iridoid glucosides named: acetylgaertneric acid (1), acetyldehydrogaertneroside (2), and dehydrogaertneric acid (10), together with 15 known compounds were isolated and identified by comparing their spectroscopic data with those in the literature. These included 9 phenylpropanoid-conjugated iridoid glucosides, acetylgaertneroside (3), gaertneroside (6), dehydrogaertneroside (7), methoxygaertneroside (8), dehydromethoxygaertneroside (9), epoxygaertneroside (11), epoxymethoxygaertneroside (12) [3], morintoside B (4) [23], and dehydroepoxymethoxygaertneroside (5) [23][24][25]; two alkaloids, N-[4′-hydroxy-3′-methoxy-(E)-cinnamoyl]-L-glutamic acid (13) [26] and (Z)-N-(p-coumaroyl)-glutamic acid (14) [27]; one benzenoid, 3,4-dihydroxybenzoic acid (15) [28]; and three flavonoid glucosides, kaempferol 3-rutinoside (16) (18) [31] (Fig. 1).…”

“…Phenylpropanoid-conjugated iridoid glucosides have been reported to be active against malaria. In our previous study, we demonstrated that two new iridoids, deglucosyl gaertneroside (19) and morindoidin (20), exhibited moderate anti-malarial activity and two known iridoids, molucidin (21) and prismatomerin (22), showed potent activity [13]. This prompted us to investigate more compounds in this plant.…”

“…To make matters even worse, there is no vaccine available for Chagas disease [15,16]. Compounds (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18) isolated during the ongoing study to identify anti-malarial compounds in M. morindoides leaves, as well as compounds (19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29) isolated during a previous study, were investigated for antitrypanosomal activity against T. cruzi.…”