Three novel dihydrochalcones from Flemingia lineata (L.) W.T. Aiton and their antiplasmodial activity.

Three novel dihydrochalcones, flemilineatins C-E (1-3), and two known flavanones (4-5) were isolated from Flemingia lineata (L.) W.T. Aiton leaves. Dihydrochalcones 1-3 structures were established using NMR spectrum and high-resolution ESIMS data. Compounds 1-5 were assayed to Plasmodium falciparum lactate dehydrogenase (PfLDH) for their antiplasmodial activity. Compounds 2 and 5 exhibited high activity with an IC50 value of 0.74 and 0.79 µg/mL, respectively.

4-Propyl- and 4-phenylcoumarins from mesua lepidota T. Anderson and their cytotoxic activity.

Two new 4-phenylcoumarins, mesulepidotins A (1) and B (2), one new 4-propylcoumarin, mesulepidotin C (3), and one known 4-phenylcoumarin (4) were isolated from Mesua lepidota stem barks. The structures of 4-propyl- and 4-phenylcoumarins were identified by analysing 1D and 2D NMR spectra combined with high-resolution ESIMS data. Compounds 1-4 were assayed to MCF-7 and HeLa cells for their cytotoxic activity. Mesulepidotin A (1) showed high activity with an IC50 value of 1.59 and 1.41 µM, respectively.

Dihydrostilbenes from Macaranga javanica (Blume) Müll. Arg. and their antiplasmodial activity.

An undescribed dihydrostilbene, macajavanicin D (1), and three known analogs, malayheyneiin A (2) and laevifolins A-B (3-4), were isolated from Macaranga javanica (Blume) Müll. Arg. leaves. Macajavanicin D (1) structure was determined based on a combination of ESI-HRMS data and NMR spectra. Compounds 1-4 were evaluated to Plasmodium falciparum strain 3D7. Macajavanicins D (1) and laevifolin A (3) showed potent activity with an IC50 value of 0.85 and 1.03 µg/mL, respectively.

Three new dihydrochalcones from the leaves of Artocarpus sericicarpus Jarrett and their activity against Plasmodium falciparum.

Three new dihydrochalcones: artoserichalcone A-C (1-3), were isolated from the leaves of Artocarpus sericicarpus. The structures of compounds were determined based on NMR spectrum (1H, 13C, and 2D) and HRESIMS spectroscopic analysis. Compounds (1) and (3) showed active antimalarial activity with IC50 values of 16.90 and 13.56 µM, respectively. Meanwhile, compound (2) with an IC50 value of 63.01 µM was categorised as a moderate antimalarial substance. The cytotoxicity against Huh7, HepG2, BHK-21, and Vero cells showed that compounds (1-3) with CC50 values > 20 µg/mL could be considered non-cytotoxic. Compounds (1-3) exhibited antimalarial activity against Plasmodium falciparum and non-toxic as an antimalarial agent.

Two new flavonols from Macaranga inermis pax & K.Hoffm.

Four isoprenylated flavonols, including two new compounds, macainermisins A-B (1-2), and two known compounds, sinoflavonoid P (3), broussoflavonol F (4), were isolated from the leaves of Macaranga inermis. A combination of HRESIMS, UV, 1D, and 2D NMR spectra elucidated the structures of 1-2. Flavonols (1-4) were evaluated against three cancer cells. Compound 1 showed high cytotoxicity against WiDR with an IC50 value of 0.93 µM, and compound 2 was active towards HeLa and WiDR (IC50 values of 0.90 and 0.94 µM), and compound 3 showed high activity towards 4T1 and HeLa (IC50 values of 0.83 and 0.98 µM).

Effect of geranylated dihydrochalcone from Artocarpus altilis leaves extract on Plasmodium falciparum ultrastructural changes and mitochondrial malate: Quinone oxidoreductase.

Nearly half of the world's population is at risk of being infected by Plasmodium falciparum, the pathogen of malaria. Increasing resistance to common antimalarial drugs has encouraged investigations to find compounds with different scaffolds. Extracts of Artocarpus altilis leaves have previously been reported to exhibit in vitro antimalarial activity against P. falciparum and in vivo activity against P. berghei. Despite these initial promising results, the active compound from A. altilis is yet to be identified. Here, we have identified 2-geranyl-2', 4', 3, 4-tetrahydroxy-dihydrochalcone (1) from A. altilis leaves as the active constituent of its antimalarial activity. Since natural chalcones have been reported to inhibit food vacuole and mitochondrial electron transport chain (ETC), the morphological changes in food vacuole and biochemical inhibition of ETC enzymes of (1) were investigated. In the presence of (1), intraerythrocytic asexual development was impaired, and according to the TEM analysis, this clearly affected the ultrastructure of food vacuoles. Amongst the ETC enzymes, (1) inhibited the mitochondrial malate: quinone oxidoreductase (PfMQO), and no inhibition could be observed on dihydroorotate dehydrogenase (DHODH) as well as bc1 complex activities. Our study suggests that (1) has a dual mechanism of action affecting the food vacuole and inhibition of PfMQO-related pathways in mitochondria.

Three novel quinolinone alkaloids from the leaves of Melicope denhamii.

Three previously unreported quinolinone alkaloids: melicodenines J-L (1-3) and six known compounds (4-9), were isolated from the leaves of Melicope denhamii (Seem) T.G. Hartley. The structures of three quinolinone alkaloids were identified based on HRESIMS and NMR spectra. Compounds 1-9 were assayed in three cancer cells (MCF-7, HeLa, and P-388). Compounds 1 and 5 showed high cytotoxic activity against HeLa cells with IC50 values of 1.8 and 0.8 µM, respectively.

Two new chromanone acids from the stem bark of Calophyllum peekelii Lauterb.

Three chromanone acids were isolated from the stem bark of Calophyllum peekelii Lauterb. Among them are two new chromanone acids, calopeekelioic acids A (1) and B (2), along with calolongic acid (3), Their structures were established by analyzing a combination of HRESIMS, 1 D, and 2 D NMR spectra. Chromanone acids 1-3 were evaluated for their antiplasmodial activity against Plasmodium falciparum strain 3D7. Compounds 1-2 showed high activity with an IC50 value of 1.70 and 1.01 µg/mL, respectively.

Two new pyranoxanthones from the stem bark of Calophyllum pseudomolle P.F. Stevens.

Two new pyranoxanthones, calotetrapterins D (1) and E (2), were isolated from the stem bark of Calophyllum pseudomolle P.F. Stevens along with α-mangostin (3). The structures of compounds 1-2 were determined based on 1D NMR (1H, 13C) and 2D NMR (HMQC, HMBC), as well as HRESIMS spectroscopic analysis. Compounds 1-2 showed moderate activity against HeLa and murine leukaemia P-388 cells.

Alkaloid and benzopyran compounds of Melicope latifolia fruit exhibit anti-hepatitis C virus activities.

BACKGROUND: New agents for developing alternative or complementary medicine to treat the hepatitis C virus (HCV) are still needed due to high rates of HCV infection globally and the current limitations of available treatments. Treatment of HCV with a combination of direct acting antivirals have been shown to be approximately 90% effective but will be limited in the future due to the emergence of drug resistance and high cost. The leaves of Melicope latifolia have previously been reported to have anti-HCV activity and are a potential source of bioactive compounds for future novel drug development. This study aimed to evaluate the efficacy of the extract of M. latifolia fruit to treat HCV and to isolate its active compounds. METHOD: M. latifolia fruit was extracted using methanol and purified using vacuum liquid chromatography (VLC) and Radial Chromatography. The anti-HCV activity was analyzed using cell culture lines Huh7it-1 and JFH1 (genotype 2a). Time-of-addition and immunoblotting studies were performed to identify the mode of action of the isolated active compounds. The structures of the active compounds were determined using nuclear magnetic resonance (NMR) spectra, UV, IR, and Mass Spectra. RESULTS: Six known compounds were isolated from M. latifolia fruit: O-methyloktadrenolon, alloevodionol, isopimpinellin, alloxanthoxyletin, methylevodionol, and N-methylflindersine. N-methylflidersine was the most active compound with IC50 value of 3.8 µg/ml while methylevodionol, isopimpinellin, and alloevodionol were less active. O-methyloktadrenolon and alloxanthoxyletin were moderately active with IC50 values of 10.9 and 21.72 µg/ml, respectively. N-methylflidersine decreased level of HCV NS3 protein expression in the cells. CONCLUSION: The alkaloid compound, N-methylflindersine which was isolated from M. latifolia possesses anti-HCV activity through post-entry inhibition and suppressed NS3 protein expression.

Calodioscurins A and B, two new isoprenylated xanthones from the stem bark of Calophyllum dioscurii P.F. Stevens.

Two new isoprenylated xanthones, calodioscurin A (1) and B (2) were isolated from the stem bark of Calophyllum dioscurii P.F. Stevens along with two known isoprenylated 4-phenylcoumarins, apetalolide (3) and methyl inophyllum P (4). The structures of two new compounds were determined based on their HRESIMS, IR, UV, 1D and 2D NMR spectral data. Compounds 1-4 were assayed on P-388 cells, compound 2 showed IC50 value 11.5 µM and categorised moderate activity.

Two novel coumarins bearing an acetophenone derivative from the leaves of Melicope Quercifolia.

Meliquercifolins A (1), and B (2), two new coumarins are bearing an acetophenone derivative were isolated from the leaves of Melicope quercifolia along with three known compounds, melicodenines E (3), F (4) and I (5). Structures of two new compounds were identified based on spectroscopic analyses (UV, HR-ESI-MS, 1 D and 2 D NMR). Cytotoxic activities of compounds (1-5) towards three human cancer cells (HeLa, MCF-7, P-388), compounds 1, 4 and 5 showed very potent activity against Hela cells with IC50 values 2.6; 0.8; 1.1 µM, respectively.

Two new 2-arylbenzofurans from Sesbania grandiflora L. and their cytotoxicity towards cancer cell.

Two new 2-arylbenzofurans, sesbagrandiflorain D (1) and E (2) along with two known 2-arylbenzofurans, spinosan A (3) and spinosan B (4) were isolated from the stem bark of Sesbania grandiflora L. The structure of two new compounds established by HRESIMS, 1 D NMR (1H, 13C) and 2 D NMR (HMQC, HMBC) spectra. Compounds (1-4) assayed for their cytotoxicity towards three human cancer cells (MCF-7, HeLa, and WiDr). Compound 1 showed very high activity against MCF-7 and WiDr with an IC50 value of 0.06 and 0.60 µg/mL, respectively.

Calotetrapterins A-C, three new pyranoxanthones and their cytotoxicity from the stem bark of Calophyllum tetrapterum Miq.

Three new pyranoxanthones, calotetrapterins A-C (1-3) were isolated from the stem bark of Calophyllum tetrapterum Miq along with three known xanthones, α-mangostin (4), garciniafuran (5), and pyranojacareubin (6). All structures were elucidated based on their IR, UV, HRESIMS, 1 D (1H, 13C) and 2 D (HMBC, HMQC) NMR spectral data. Compounds 1-6 were tested to P-388 cells for cytotoxic activity, compound 2 exhibited high activity with IC50 value 1.0 µM.

Review: Secondary Metabolites of Aquilaria, a Thymelaeaceae Genus.

BACKGROUND: Aquilaria, a genus belonging to the Thymelaeaceae, produces fragrant resinous agarwood, also known as eaglewood, which has been used as incense since old times. The intense fra-grance is the result of the presence of a wide variety of secondary metabolites. OBJECTIVE: This genus was reported contained sesquiterpenes, chromones, flavonoids, benzophenones, diterpenoids, triterpenoids, and lignans. CONCLUSION: Here, we review the different secondary metabolites that have been identified in Aquilaria to show their diversity and to allow comparison with other Thymelaeaceae genera.

Mesucalophylloidin, a new isoprenylated 4-phenylcoumarin from Mesua calophylloides (Ridl.) Kosterm.

A new isoprenylated 4-phenylcoumarin derivative, mesucalophylloidin (1) along with three known compounds, mammea A/BA cyclo F (2), calolongic acid (3) and isocalolongic acid (4) were isolated from the stem bark of Mesua calophylloides (Ridl.) Kosterm. Structures of all the compounds were elucidated using extensive spectroscopic methods, including UV, IR, HRESIMS, 1D and 2D NMR. Compounds 1-4 were evaluated for their cytotoxicity against P-388 cells, showing that compound 1 gave moderate activity with IC50 6.26 µg/mL.

Airlanggins A-B, two new isoprenylated benzofuran-3-ones from the stem bark of Calophyllum soulattri.

Two new isoprenylated benzofuran 3-ones, airlanggin A (1) and B (2) along with two known xanthones, ananixanthone (3) and trapezifolixanthone (4) were isolated from the stem bark of Calophyllum soulattri. Structures of all the compounds were elucidated using extensive spectroscopic methods, including UV, IR, HRESIMS, 1D and 2D NMR. Compounds 1-4 were evaluated for their cytotoxicity against P-388 cells, showing that compound 3 was the most active with IC50 0.68 µg/mL and compound 1 showed moderate activity with IC50 5.80 µg/mL.

Flavonoid and stilbene derivatives from Macaranga trichocarpa.

A new farnesylated flavonol (4'-O-methylmacagigantin) and a new geranylated stilbene (macatrichocarpin H), together with eight known phenolic compounds, have been isolated from the leaves of Macaranga trichocarpa. Structures of these compounds were determined based on NMR and mass spectrroscopic data. Cytotoxic properties of the isolated compounds were tested against P-388 cells showing that mactrichocarpin G was the most active compound with IC50 was 3.5µM.

Antiplasmodial Activity of Isolated Polyphenols from Alectryon serratus Leaves Against 3D7 Plasmodium falciparum.

BACKGROUND: Alectryon serratus was selected from a screening program devoted to search naturally occurring antimalarial compound from plants in Alas Purwo National Park, Banyuwangi, East Java, Indonesia. The previous studies showed that ethanol extract of A. serratus leaves contains some polyphenol compounds. OBJECTIVE: This study was designed to isolate and investigate antiplasmodial activity of polyphenol compounds. MATERIAL AND METHODS: The ethanol extract of A. serratus leaves was fractioned using liquid-liquid fractionation and column chromatography. Isolated compounds were identified using High-performance liquid chromatography, ultraviolet-visible, nuclear magnetic resonance, and compared with references. The isolates were tested in vitro for antiplasmodial activity against chloroquine-sensitive 3D7 strain of Plasmodium falciparum. Thin blood smears were used to assess the levels of parasitemia and growth inhibition of the isolates. RESULT: Half maximal Inhibitory concentration of Gallic acid (1), methyl gallate (2), and kempferol-3-O-rhamnoside (3) were 0.0722 µM, 0.0128 µM, and 3.4595 µM, respectively. CONCLUSION: The results suggest that gallic acid, methyl gallate, and kempferol-3-O-rhamnoside isolated from A. serratus leaves have antiplasmodial activity and are potential to be developed as antimalarial drugs. SUMMARY: The ethanol extract of Alectryon serratus leaves was successively fractionated in CH2Cl2, EtOAc, and n-butanol. EtOAc fraction was fractionated using column chromatography and purified using preparative thin-layer chromatography (TLC). Isolates were studied for their antiplasmodial activity on parasites culture of chloroquine-sensitive 3D7 strain of Plasmodium falciparum. Parasitemia percentages, growth percentages, and inhibition percentages of each group were calculated. The half maximal inhibitory concentration (IC50) values that represent the concentration required to inhibit 50% of Plasmodium growth were calculated from a calibration curve using linear regression. The results suggest that isolates have antiplasmodial activity and are responsible in the antimalarial activity of Alectryon serratus leaves. Abbreviations Used: S.F: Subfraction, EGCG: Epigallocatechingallate, EGC: Epigallocatechin.

Dihydroflavonol and flavonol derivatives from Macaranga recurvata.

Two new dihydroflavonol derivatives, macarecurvatins A and B, have been isolated from the leaves of Macaranga recurvata (Euphorbiaceaae), along with the known compounds diisoprenylaromadendrin, glyasperin A and broussoflavonol F. The structures of the new compounds were determined on the basis of spectroscopic evidence. Upon cytotoxic evaluation against P-388 cells, macarecurvatin B showed strong activity with an IC50 of 0.83 microM.