Triterpenoid saponins from a cytotoxic root extract of Sideroxylonfoetidissimum subsp. gaumeri

Evaluation of the cytotoxicity of an ethanolic root extract of Sideroxylonfoetidissimum subsp. gaumeri (Sapotaceae) revealed activity against the murine macrophage-like cell line RAW 264.7. Systematic bioassay-guided fractionation of this extract gave an active saponin-containing fraction from which four saponins were isolated. Use of 1D (¹H, ¹³C, DEPT135) and 2D (COSY, TOCSY, HSQC, and HMBC) NMR, mass spectrometry and sugar analysis gave their structures as 3-O-(β-d-glucopyranosyl-(1 → 6)-β-d-glucopyranosyl)-28-O-(α-l-rhamnopyranosyl-(1 → 3)[β-d-xylopyranosyl-(1 → 4)]-β-d-xylopyranosyl-(1 → 4)-α-l-rhamnopyranosyl-(1 → 2)-α-l-arabinopyranosyl)-16α-hydroxyprotobassic acid, 3-O-β-d-glucopyranosyl-28-O-(α-l-rhamnopyranosyl-(1 → 3)[β-d-xylopyranosyl-(1 → 4)]-β-d-xylopyranosyl-(1 → 4)-α-l-rhamnopyranosyl-(1 → 2)-α-l-arabinopyranosyl)-16α-hydroxyprotobassic acid, 3-O-(β-d-glucopyranosyl-(1 → 6)-β-d-glucopyranosyl)-28-O-(α-l-rhamnopyranosyl-(1 → 3)-β-d-xylopyranosyl-(1 → 4)[β-d-apiofuranosyl-(1 → 3)]-α-l-rhamnopyranosyl-(1 → 2)-α-l-arabinopyranosyl)-16α-hydroxyprotobassic acid, and the known compound, 3-O-β-d-glucopyranosyl-28-O-(α-l-rhamnopyranosyl-(1 → 3)[β-d-xylopyranosyl-(1 → 4)]-β-d-xylopyranosyl-(1 → 4)-α-l-rhamnopyranosyl-(1 → 2)-α-l-arabinopyranosyl)-protobassic acid. Two further saponins were obtained from the same fraction, but as a 5:4 mixture comprising 3-O-(β-d-glucopyranosyl)-28-O-(α-l-rhamnopyranosyl-(1 → 3)-β-d-xylopyranosyl-(1 → 4)[β-d-apiofuranosyl-(1 → 3)]-α-l-rhamnopyranosyl-(1 → 2)-α-l-arabinopyranosyl)-16α-hydroxyprotobassic acid and 3-O-(β-d-apiofuranosyl-(1 → 3)-β-d-glucopyranosyl)-28-O-(α-l-rhamnopyranosyl-(1 → 3)[β-d-xylopyranosyl-(1 → 4)]-β-d-xylopyranosyl-(1 → 4)-α-l-rhamnopyranosyl-(1 → 2)-α-l-arabinopyranosyl)-16α-hydroxyprotobassic acid, respectively. This showed greater cytotoxicity (IC₅₀ = 11.9 ± 1.5 μg/ml) towards RAW 264.7 cells than the original extract (IC₅₀ = 39.5 ± 4.1 μg/ml), and the saponin-containing fraction derived from it (IC₅₀ = 33.7 ± 6.2 μg/ml).     

Isolation of anti-Candida albicans compounds from Markhamia obtusifolia (Baker) Sprague (Bignoniaceae)

An increase in clinical cases of Candidiosis globally as well as fungal resistance to drugs prompted the search for novel anti-Candida albicans agents from plant sources. Leaf extracts of Markhamia obtusifolia were screened for activity against C. albicans in vitro. An acetone extract obtained following serial exhaustive extraction contained mainly the active components with at least four active zones on the bioautogram. Bioassay guided fractionation of this extract led to the isolation of three compounds which inhibited the growth of three C. albicans strains. Based on spectroscopy studies (NMR and MS), the compounds were identified as 3β-hydroxyurs-12-en-28-oic acid, ursolic acid (1) 3β, 19α-dihydroxyurs-12-en-28-oic acid, pomolic acid (2) and 2β, 3β, 19α -trihydroxy-urs-12-en-28-oic acid, 2-epi-tormentic acid (3). The most active compound was 3β, 19α-dihydroxy-12-ursen-28-oic acid (2) with a minimum inhibitory concentration (MIC) value of 12.5 µg/mL for C. albicans isolated from dog and 25.0 µg/mL for C. albicans from cat and ATCC 90028 at 24 h following incubation. However, at 48 h of incubation MICs were > 400 µg/mL for all the three compounds isolated. This study indicated that M. obtusifolia could be a potential source of active principles against C. albicans.     

Dammarane triterpenes from Cabralea canjerana (Vell.) Mart. (Meliaceae): Their chemosystematic significance

The stem of Cabralea canjerana (Vell.) Mart. yielded three new dammarane triterpenes 20S,24S-epoxy-7β,25-dihydroxy-3,4-secodammar-4(28)-en-3-oic acid, 20S,24S-epoxy-7β,15α,25-trihydroxy-3,4-secodammar-4(28)-en-3-oic acid and 20S,24R-epoxy-7β,22ξ,25-trihydroxy-3,4-secodammar-4(28)-en-3-oic acid, which were identified on the basis of spectroscopic methods. The known dammarane triterpenes ocotillone, eichlerianic acid, shoreic acid and the sterols sitosterol, campesterol, stigmasterol, sitostenone and stigmast-5-en-3-one were also isolated and identified. The branches yielded the above three known dammaranes and eichlerialactone. The dammaranes in C. canjerana display strong similarities with Trichilieae tribe, which contains several dammaranes. The data reported herein thus provide firm support for placing Cabralea within the subfamily Melioideae, Trichilieae tribe.     

ent-Labdane diterpenes from the aquatic plant Potamogeton pectinatus

Four new ent-labdane diterpenes were isolated from the freshwater aquatic plant Potamogeton pectinatus, together with two known furano-ent-labdanes. The new compounds were assigned the structures methyl-15,16-epoxy-12(R)-acetoxy- 8(17), 13(16),14-ent-labdatrien-19-oate,15,16-epoxy-12(R)-acetoxy-8(17), 13(16),14-ent-labdatrien-19-oic acid, 8(17),13-ent-labdadien-15 --> 16-lactone-19-oic acid and 16-hydroxy-8(17),13-ent-labdadien-15,16-olid-19-oic acid by spectroscopic means. Some of these labdanes showed a strong algicidal activity against Raphidocelis subcapitata.     

Triterpenoidal saponins of Pulsatilla koreana roots

Sixteen (1-16) triterpenoidal saponins were isolated from the roots of Pulsatilla koreana, of which four were determined as the previously unknown 23-hydroxy-3β-[(O-α-L-arabinopyranosyl)oxy]lup-20(29)-en-28-oic acid 28-O-β-D-glucopyranosyl ester (1), 23-hydroxy-3β-[(O-α-L-rhamnopyranosyl-(1 → 2)-α-L-arabinopyranosyl)oxy]lup-20(29)-en-28-oic acid 28-O-β-D-glucopyranosyl ester (2), 3β-[(O-α-L-rhamnopyranosyl-(1 → 2)-α-L-arabinopyranosyl)oxy]lup-20(29)-en-28-oic acid 28-O-β-D-glucopyranosyl-(1 → 6)-β-D-glucopyranosyl ester (3), and 3β-[(O-α-L-rhamnopyranosyl-(1 → 2)-O-[β-D-glucopyranosyl-(1 → 4)]-α-L-arabinopyranosyl)oxy]lup-20(29)-en-28-oic acid 28-O-α-L-rhamnopyranosyl-(1 → 4)-O-β-D-glucopyranosyl-(1 → 6)-β-D-glucopyranosyl ester (4), respectively, based on spectroscopic analysis. The inhibition of the lipopolysaccharide-induced nitric oxide production of sixteen isolated compounds was evaluated in RAW 264.7 cells at concentrations ranging from 1 μM to 100 μM.     

Ent-kaurane derivatives from the root cortex of yacon and other three Smallanthus species (Heliantheae,Asteraceae)

The metabolites produced by the secretory canals of the root cortex from four Smallanthus species belonging to the yacon group were identified as ent-kaurane-type diterpenes. The dichloromethane root cortex extracts of the four species were treated with diazomethane and analyzed comparatively by GC–MS using a simple and rapid procedure which is very sensitive and reproducible permitting detection of minor components. In all cases, ent-16-kauren-19-oic acid (kaurenoic acid) methyl ester was the main component, differences being observed only in the minor components. The minor components identified were grandiflorenic acid methyl ester, ent-16-kauren-19-al, 16α,17-epoxy-15α-angeloyloxy-kauran-19-oic acid methyl ester and several O-acyl derivatives at C-15 or C-18 of kaurenoic acid. One of the minor components, 18-isobutyroyloxy-ent-kaur-16-en-19-oic acid is a new kaurenoic acid derivative. Grandiflorenic acid and 15-α-angeloyloxy-16,17-α-epoxy-ent-16-kauren-19-oic acid were present only in Smallanthus sonchifolius and Smallanthus siegesbeckius which showed very similar GC traces. The different GC profile of RC diterpenes from Smallanthus connatus and Smallanthus macroscyphus supports the view that they are different taxa. Some chemotaxonomic aspects of the genus Smallanthus and the subtribe Milleriinae are briefly discussed.     

Isopimarane diterpene glycosides, apoptosis inducers, obtained from fruiting bodies of the ascomycete Xylaria polymorpha

The methanol extract of fruiting bodies of the ascomycete Xylaria polymorpha afforded three isopimarane diterpene glycosides, namely, 16-α-d-mannopyranosyloxyisopimar-7-en-19-oic acid (1), 15-hydroxy-16-α-d-mannopyranosyloxyisopimar-7-en-19-oic acid (2), and 16-α-d-glucopyranosyloxyisopimar-7-en-19-oic acid (3). Their structures were determined by spectroscopic methods and by single-crystal X-ray analysis. They showed cytotoxicity against human cancer cell lines and exhibited IC₅₀ values ranging from 71 to 607 μM. Further studies on the cytotoxicity of these compounds against HL60 cells demonstrated that they induced apoptosis along with typical DNA fragmentation. It was observed that 2 was less active than 1 and 3.     

Antimalarial compounds from Schefflera umbellifera

The organic extract of the leaves of Schefflera umbellifera exhibited good antimalarial activity when tested against the chloroquine-susceptible strain (D10). Bioassay-guided fractionation of the dichloromethane fraction of the dichloromethane/methanol extract yielded an active compound, betulin, which exhibited good antiplasmodial activity with an IC₅₀ value of 3.2 µg/ml. The reference compound, chloroquine gave an IC₅₀ value of 27.2 ng/ml. Two other compounds were also isolated from the dichloromethane extract namely, 7-hydroxy-6-methoxycoumarin and ent-kaur-16-en-19-oic acid. These two compounds did not exhibit any significant antiplasmodial activity.     

Bioactive saponins from Microsechium helleri and Sicyos bulbosus

Eleven oleanane-type saponins (1-11) have been isolated from Microsechium helleri and Sicyos bulbosus roots and were evaluated for their antifeedant, nematicidal and phytotoxic activities. Saponins {3-O-β-d-glucopyranosyl (1 → 3)-β-d-glucopyranosyl-2β,3β,16α,23-tetrahydroxyolean-12-en-28-oic acid 28-O-α-l-rhamnopyranosyl-(1 → 3)-β-d-xylopyranosyl-(1 → 4)-[β-d-xylopyranosyl-(1 → 3)]-α-l-rhamnopyranosyl-(1 → 2)-α-l-arabinopyranoside} (1), and {3-O-β-d-glucopyranosyl-2β,3β,16α,23-tetrahydroxyolean-12-en-28-oic acid 28-O-α-l-rhamnopyranosyl-(1 → 3)-β-d-xylopyranosyl-(1 → 4)-[β-d-xylopyranosyl-(1 → 3)]-α-l-rhamnopyranosyl-(1 → 2)-α-l-arabinopyranoside} (2) were also isolated from M. helleri roots together with the two known compounds 3 and 4. Seven known structurally related saponins (5-11) were isolated from S. bulbosus roots. The structures of these compounds were established as bayogenin and polygalacic glycosides using one- and two-dimensional NMR spectroscopy and mass spectrometry. Compounds 7, 10, bayogenin (12) and polygalacic acid (13) showed significant (p < 0.05) postingestive effects on Spodoptera littoralis larvae, compounds 5-11 and 12 showed variable nematicidal effects on Meloydogyne javanica and all tested saponins had variable phytotoxic effects on several plant species (Lycopersicum esculentum, Lolium perenne and Lactuca sativa). These are promising results in the search for natural pesticides from the Cucurbitaceae family.     

Antimalarial sesquiterpene lactones from Distephanus angulifolius

Combined use of bioassay-guided fractionation based on in vitro antiplasmodial assay and dereplication based on HPLC-PDA-MS-SPE-NMR led to isolation of (6S,7R,8S)-14-acetoxy-8-[2-hydroxymethylacrylat]-15-helianga-1(10),4,11(13)-trien-15-al-6,12-olid and (5R,6R,7R,8S,10S)-14-acetoxy-8-[2-hydroxymethylacrylat]-elema-1,3,11(13)-trien-15-al-6,12-olid, along with vernodalol, vernodalin, and 11,13β-dihydroxyvernodalin from extract of Distephanus angulifolius. All compounds were identified by spectroscopic methods, including 1D and 2D homo- and heteronuclear NMR experiments. The isolated compounds showed IC₅₀ values in the range 1.6-3.8 μM and 2.1-4.9 μM against chloroquine sensitive D10 and chloroquine resistant W2 Plasmodium falciparum strains, respectively.     

A sensitive liquid chromatography–electrospray tandem mass spectrometric method for lancemaside A and its metabolites in plasma and a pharmacokinetic study in mice

A high-performance liquid chromatography tandem mass spectrometry (HPLC–MS/MS) method employing electrospray ionization (ESI) has been developed for simultaneous determination of lancemaside A (3-O-β-d-glucuronopyranosyl-3β, 16α-dihydroxyolean-12-en-28-oic acid 28-O-β-d-xylopyranosyl(1→3)-β-d-xylopyranosyl-(1→4)-α-l-rhamnopyranosyl-(1→2)-α-l-arabinopyranosyl ester) and its metabolites in mouse plasma. When lancemaside A (60 mg/kg) was orally administered to mice, echinocystic acid was detected in the blood. T_max and C_max of the echinocystic acid were 6.5 ± 1.9 h and 56.7 ± 29.1 ppb. Orally administered lancemaside A was metabolized to lancemaside X (3β, 16α-dihydroxyolean-12-en-28-oic acid 28-O-β-d-xylopyranosyl(1→3)-β-d-xylopyranosyl-(1→4)-α-l-rhamnopyranosyl-(1→2)-α-l-arabinopyranosyl ester) by intestinal microflora in mice, which was metabolized to echinocystic acid by intestinal microflora and/or intestinal tissues. Human intestinal microflora also metabolized lancemaside A to echinocystic acid via lancemaside X. These results suggest that the metabolism by intestinal microflora may play an important role in pharmacological effects of orally administered lancemaside A.     

Estrogenic activities of Psoralea corylifolia L. seed extracts and main constituents

Estrogenic activities of ethanol extract and its active components from Psoralea corylifolia L. were studied using various in vitro assays. The main components from ethanol extract were analyzed to be bakuchiol, psoralen, isobavachalcone, isobavachromene, and bavachinin. In a fractionation procedure, hexane and chloroform fractions showed estrogenic activity in yeast transactivation assay and E-screen assay. In yeast transactivation assay, ethanol extract, hexane, and chloroform fractions showed significantly higher activities at a concentration of 1.0 ng/ml, and bakuchiol at the concentration of 10⁻⁶ M was showed the highest activity, especially, which was higher than genistein at the same concentration. In E-screen assay, cell proliferation of bakuchiol (10⁻⁶ M) showed similar estrogenic activity with genistein (10⁻⁶ M). In ER binding assay, bakuchiol displayed the strongest ER-binding affinity (IC₅₀ for ERα = 1.01 × 10⁻⁶ M, IC₅₀ for ERβ = 1.20 × 10⁻⁶ M) and bakuchiol showed five times higher affinity for ERα than for ERβ.     

Acylated flavonol tetraglycosides from Delphinium gracile

An ethanol extract of the aerial parts of Delphinium gracile DC. yielded five flavonol glycosides quercetin-3-O-{[β-d-xylopyranosyl (1 → 3)-4-O-(E-p-caffeoyl)-α-l-rhamnopyranosyl (1 → 6)][β-d-glucopyranosyl (1 → 2)]}-β-d-glucopyranoside (1), quercetin-3-O-{[β-d-xylopyranosyl (1 → 3)-4-O-(E-p-coumaroyl)-α-l-rhamnopyranosyl (1 → 6)][β-d-glucopyranosyl (1 → 2)]}-β-d-glucopyranoside (2), quercetin-3-O-{[β-d-xylopyranosyl (1 → 3)-4-O-(Z-p-coumaroyl)-α-l-rhamnopyranosyl (1 → 6)][β-d-glucopyranosyl (1 → 2)]}-β-d-glucopyranoside (3), kaempferol-3-O-{[β-d-glucopyranosyl (1 → 3)-4-O-(E-p-coumaroyl)-α-l-rhamnopyranosyl (1 → 6)][β-d-glucopyranoside-7-O-(4-O-acetyl)-α-l-rhamnopyranoside (4) kaempferol-3-O-{[β-d-glucopyranosyl (1 → 3)-4-O-(E-p-coumaroyl)-α-l-rhamnopyranosyl (1 → 6)][β-d-glucopyranoside-7-O-(4-O-acetyl)-α-l-rhamnopyranoside (5) in addition to 4-(β-d-glucopyranosyloxy)-6-methyl-2H-pyran-2-one (6) and rutin. Structures were elucidated by spectroscopic methods.     

Rearranged abietane diterpenoids from the root of Teucrium lanigerum

A new rearranged abietane diterpenoid, teuvincenone J, was isolated from the root of Teucrium lanigerum Lag. (Labiatae) together with four known compounds, teuvincenones A–D. The structure of the new diterpene [12,16-epoxy-11,14-dihydroxy-17(15 → 16)-abeo-3α,18-cyclo-8,11,13,15-abietatetraen-7-one] was established by 1D- and 2D-NMR spectroscopic means. These diterpenes could be significant from a chemotaxonomic point of view.     

Purification and biochemical characterization of Eumiliin from Euphorbia milii var. hislopii latex

A protease, which we designate Eumiliin, was isolated from the latex of Euphorbia milii var. hislopii by a combination of ion-exchange chromatographic steps using DEAE-Sephacel and gel-filtration with Sephadex G-75. Eumiliin is a monomeric protein with an apparent molecular mass of 30 kDa by SDS-PAGE under reducing conditions and gave one main peak at 29,814 KDa in MALDI-TOF/TOF mass spectrometry. Eumiliin has caseinolytic and fibrinogenolytic activities, but no hemorrhagic or defibrinating activities. The enzyme readily hydrolyzes the Aα-chain of fibrinogen and, more slowly, the Bβ-chain. Its fibrinogenolytic activity is inhibited by β-mercaptoethanol and leupeptin. In contrast, EDTA and benzamidine did not affect the activity of Eumiliin. The caseinolytic activity of Eumiliin had a pH optimum of 8.0 and was stable in solution at up to 40 °C; activity was completely lost at ?80 °C. Intraplantar injection of Eumiliin (1-25 μg/paw) caused a dose- and time-dependent hyperalgesia, which peaked 1-5 h after enzyme injection. Intraplantar injection of Eumiliin (1-25 μg/paw) also caused an oedematogenic response that was maximal after 1 h. Morphological analyses indicated that Eumiliin induced an intense myonecrosis, with visible leukocyte infiltrate and damaged muscle cells 24 h after injection.     

Cytotoxic triterpenoid saponins from the stem bark of Antonia ovata

Phytochemical investigation of the MeOH extract of the stem bark of Antonia ovata led to the isolation of four triterpenoid saponins, along with eleven known compounds. Their structures were established by extensive 1D and 2D NMR, as well as HR-MS analysis and acid hydrolysis. All isolated saponins contained the same tetrasaccharide chain O-β-d-xylopyranosyl-(1 → 2)-O-β-d-glucopyranosyl-(1 → 3)-O-[β-d-glucopyranosyl-(1 → 2)]-β-d-glucuropyranoside linked to C-3 of esterified derivatives of R₁-barrigenol, A₁-barrigenol, barringtogenol C, or camelliagenin. Biological evaluation of the compounds against KB cell line revealed a potent cytotoxic activity with IC₅₀ values ranging from 3.1 to 6.6 μM. The known compounds were found to be inactive at 10 μg/ml concentration.     

Cycloartane-type glycosides from Astragalus amblolepis

Five cycloartane-type triterpene glycosides were isolated from the methanol extract of the roots of Astragalus amblolepis Fischer along with one known saponin, 3-O-β-D-xylopyranosyl-16-O-β-D-glucopyranosyl-3β,6α,16β,24(S),25-pentahydroxy-cycloartane. Structures of the compounds were established as 3-O-β-D-xylopyranosyl-25-O-β-D-glucopyranosyl-3β,6α,16β,24(S),25-pentahydroxy-cycloartane, 3-O-[β-D-glucuronopyranosyl-(1 → 2)-β-D-xylopyranosyl]-25-O-β-D-glucopyranosyl-3β,6α,16β,24(S),25-pentahydroxy-cycloartane, 3-O-β-D-xylopyranosyl-24,25-di-O-β-D-glucopyranosyl-3β,6α,16β,24(S),25-pentahydroxy-cycloartane, 6-O-α-L-rhamnopyranosyl-16,24-di-O-β-D-glucopyranosyl-3β,6α,16β,24(S),25-pentahydroxy-cycloartane, 6-O-α-L-rhamnopyranosyl-16,25-di-O-β-D-glucopyranosyl-3β,6α,16β,24(S),25-pentahydroxy-cycloartane by using 1D and 2D-NMR techniques and mass spectrometry. To the best of our knowledge, the glucuronic acid moiety in cycloartanes is reported for the first time.     

Bacterial resistance modifying tetrasaccharide agents from Ipomoea murucoides

As part of an ongoing project to identify oligosaccharides which modulate bacterial multidrug resistance, the CHCl₃-soluble extract from flowers of a Mexican arborescent morning glory, Ipomoea murucoides, through preparative-scale recycling HPLC, yielded five lipophilic tetrasaccharide inhibitors of Staphylococcusaureus multidrug efflux pumps, murucoidins XII-XVI (1-5). The macrocyclic lactone-type structures for these linear hetero-tetraglycoside derivatives of jalapinolic acid were established by spectroscopic methods. These compounds were tested for in vitro antibacterial and resistance modifying activity against strains of Staphylococcus aureus possessing multidrug resistance efflux mechanisms. Only murucoidin XIV (3) displayed antimicrobial activity against SA-1199B (MIC 32 μg/ml), a norfloxacin-resistant strain that over-expresses the NorA MDR efflux pump. The four microbiologically inactive (MIC > 512 μg/ml) tetrasaccharides increased norfloxacin susceptibility of this strain by 4-fold (8 μg/ml from 32 μg/ml) at concentrations of 25 μg/ml, while murucoidin XIV (3) exerted the same potentiation effect at a concentration of 5 μg/ml.     

Diterpenoids from the pericarp of Platycladus orientalis

Eight labdane-type diterpenes, 7beta,13S-dihydroxylabda-8(17),14-dien-19-oic acid (1), 12R,15-dihydroxylabda-8(17),13E-dien-19-oic acid (3c), 12R,15-dihydroxylabda-8(17),13Z-dien-19-oic acid (3d), 12R,13R,14S-trihydroxylabda-12,15-epoxy-8(17)-en-19-oic acid (4a), 12S,13S,14R-trihydroxylabda-12,15-epoxy-8(17)-en-19-oic acid (4b), 15-hydroxy-12-oxolabda-8(17),13E-dien-19-oic acid (5), 14R,15-dihydroxylabda-8(17),12Z-dien-19-oic acid (7a) and 14S,15-dihydroxylabda-8(17),12Z-dien-19-oic acid (7b), along with 20 known diterpenoids, were isolated from the pericarp of Platycladus orientalis. Their structures were unambiguously elucidated by NMR spectroscopic and single crystal X-ray diffraction analyses, as well as via chemical correlation conversion. NMR spectroscopic data of known isomers 8c and 8d were reported as a supplement to existing data.     

Leishmanicidal effect of LLD-3 (1), a nor-triterpene isolated from Lophanthera lactescens

Leishmanicidal activity of 6α, 7α, 15β, 16β, 24-pentacetoxy-22α-carbometoxy-21β,22β-epoxy-18β−hydroxy-27,30-bisnor-3,4-secofriedela-1,20 (29)-dien-3,4 R-olide (LLD-3 (1)) isolated from Lophanthera lactescens Ducke, a member of the Malpighiaceae, was demonstrated against intramacrophage amastigote forms (IC₅₀ of 0.41 μg/mL). The in vitro leishmanicidal effect of Glucantime, the first choice drug for leishmaniasis treatment, was increased by LLD-3 (1) association. The leishmanicidal effect of LLD-3 (1) was not due to stimulation of nitric oxide production by macrophages. LLD-3 (1) was also not cytotoxic for mouse peritoneal macrophages or B cells as assessed by the XTT and Trypan blue exclusion assays. LLD-3 (1) was unable to affect proliferation of naïve or activated B and T cells, as well as the B cells immunoglobulin synthesis. Cellularity of different tissues, liver and kidney functions were not altered in mice treated with LLD-3 (1), as well as the histology pattern of different organs. Our results add LLD-3 (1) as a potential drug candidate for treatment of leishmaniasis.