Cytotoxic phenolic compounds isolated from the fruits of Macaranga denticulata.

A new modified geranylated flavonoid, 3'-dehydroxy-solophenol C (1), along with 17 known compounds (2-18) were isolated from the fruits of Macaranga denticulata. Their structures were established by spectral analysis, such as mass spectrometry, 1D-NMR and 2D-NMR. The new geranylated flavonoid 1 showed a moderate cytotoxic activity against the A549 cell line with IC50 value of 16.0 µM. Compound 9 showed the highest cytotoxic activities against KB, HepG2, Lu-1 and MCF7 cell lines with IC50 values of 0.6, 0.8, 1.3 and 1.2 µM, respectively.

Antimicrobial lavandulylated flavonoids from a sponge-derived actinomycete.

Analysis of an antimicrobial culture broth extract of the sponge-derived actinomycete Streptomyces sp. (strain G246) led to the isolation of two new lavandulylated flavonoids, 6-lavandulyl-7-methoxy-5,2',4'-trihydroxylflavanone (1) and 5'-lavandulyl-4'-methoxy-2,4,2',6'-tetrahydroxylchalcone (2), along with eight known compounds 3-10. Their structures were established by spectral data analysis, including MS, 1D, 2D-NMR and CD. The absolute configurations of 1 and 2 were suggested by comparison of their experimental and calculated electronic circular dichroism spectra. All the isolated compounds were evaluated for their antimicrobial activity against a panel of clinically significant microorganisms. Compounds 1 and 2 had a broad-spectrum of antimicrobial activity. Additionally, except the strain Escherichia coli, compound 2 exhibited remarkable inhibitory activity against Pseudomonas aeruginosa, Salmonella enterica, Enterococcus faecalis, Staphylococcus aureus, Bacillus cereus, and Candida albicans strains.

New flavonoid and stilbene derivatives from the fruits of Macaranga balansae.

Two new prenylated flavonoids, 4´-methyl-8-prenyltaxifolin (1) and 6,8-diprenyl-4´-methyl-naringenin (2) and a new geranylated stilbene, 4'-deprenyl-4-methoxymappain (3) together with eight known flavonoids (4-11) were isolated from the fruits of Macaranga balansae Gagnep. Their chemical structures were determined by means of spectroscopic methods including 1D, 2D NMR, and MS data. Compound 2 showed the highest cytotoxic activity against PanC1, A549, KB and LU-1 cell lines with IC50 values range from 7.89 to 22.81 µM.

Triterpene glycosides from the Vietnamese sea cucumber Holothuria edulis.

From the MeOH extract of the Vietnamese sea cucumber Holothuria edulis, eight triterpene glycosides (1-8), including one new compound namely holothurin A5 (1), were isolated by using various chromatographic separations. Their structures were established by spectroscopic experiments including 1D, 2D NMR and HR-ESI-MS. Holothurin A5 (1) has a hydroperoxy group at C-25. To the best of our knowledge, this is the first report of this group in triterpene saponins obtained from sea cucumbers to date. In addition, the in vitro cytotoxicity against five human cancer cell lines (HepG2, KB, LNCaP, MCF7 and SK-Mel2) of all isolated compounds was also evaluated using SRB assays.

Briarane-type diterpenoids from the Vietnamese gorgonian Junceella fragilis.

Ten briarane-type diterpenoids (1-10), including one new stereoisomer 17-epi-junceellolide B (1), were isolated from the MeOH extract of the Vietnamese gorgonian Junceella fragilis. Their structures were elucidated by spectroscopic experiments including 1D and 2D NMR, and HR-QTOF-MS. In addition, the in vitro cytotoxic activity against eight human cancer cell lines (LNCaP, HepG2, KB, MCF-7, SK-Mel2, HL-60, LU-1 and SW480) of all isolated compounds was evaluated by SRB assays.

Cytotoxic lignans from fruits of Cleistanthus tonkinensis.

Seven new lignans, cleistonkinins A- E (1-5), cleistonkisides A and B (6-7) were isolated from the fruits of Cleistanthus tonkinensis (Euphorbiaceae), together with five known aryltetralin lignans, cleisindoside B (8), cleistantoxin (9), cleisindoside D (10), neocleistantoxin (11) and polygamain (12). Their structures were established from spectral analysis, including mass spectrometry and 2D-NMR. The absolute configurations of 4-7 were determined by analysis of their experimental CD spectra and comparison with calculated electronic circular dichroism (ECD) spectra. Compounds 2 and 6 had selective inhibition with moderate cytotoxicity against Pan C1 and A549 cell lines, respectively. Cleistantoxin (9) was significantly active against A549, HeLa, Hep3B, Pan C1 and MCF7 cell lines while it was less cytotoxic against HeLa cells. Neocleistantoxin (11) exhibited remarkable inhibition toward A549, HeLa, MCF7 and Pan C1. This is the first report for cytotoxicity of 9 and 11 against A549, Hep3B and Pan C1 cell lines.

Cytotoxic Phenolic Compounds from Fruit Glandular Trichomes of Macaranga tanarius.

A new flavonoid, macatanarin D (1), together with five known stilbenes (2-6), was isolated from fruit glandular trichomes of Macaranga tanarius. Their structures were elucidated on the basis of spectroscopic methods and through comparison with data reported in the literature. All isolated compounds were evaluated for their cytotoxic activities against KB and MCF-7 cell lines. Compounds 3, 4, and 5 showed the strongest activities against both cell lines with IC50 values in the range of 0.03-0.12 µM, and compound 2 only showed a significant cytotoxicity against KB cell line (IC50 = 0.26 µM) and a moderate cytotoxicity against MCF-7 (IC50 = 10.4 µM). Compounds 1 and 6 showed weak cytotoxic activities against KB cell line with IC50 values of 29.3 and 24.7 µM, respectively.

Chemical Composition and Biological Activities of Metabolites from the Marine Fungi Penicillium sp. Isolated from Sediments of Co To Island, Vietnam.

Marine microorganisms are an invaluable source of novel active secondary metabolites possessing various biological activities. In this study, the extraction and isolation of the marine sediment Penicillium species collected in Vietnam yielded ten secondary metabolites, including sporogen AO-1 (1), 3-indolecarbaldehyde (2), 2-[(5-methyl-1,4-dioxan-2-yl)methoxy]ethanol (3), 2-[(2R-hydroxypropanoyl)amino]benzamide (4), 4-hydroxybenzandehyde (5), chrysogine (6), 3-acetyl-4-hydroxycinnoline (7), acid 1H-indole-3-acetic (8), cyclo (Tyr-Trp) (9), and 2',3'-dihydrosorbicillin (10). Their structures were identified by the analysis of 1D and 2D NMR data. Among the isolated compounds, 2-[(5-methyl-1,4-dioxan-2-yl)methoxy]ethanol (3) showed a strong inhibitory effect against Enterococcus faecalis with a minimum inhibitory concentration value of 32 µg/mL. Both 2-[(2R-hydroxypropanoyl)amino]benzamide (4) and 4-hydroxybenzandehyde (5) selectively inhibited E. coli with minimum inhibitory concentration values of 16 and 8 µg/mL, respectively. 2',3'-Dihydrosorbicillin (10) potentially inhibited α-glucosidase activity at a concentration of 2.0 mM (66.31%).

Antimicrobial Lavandulylated Flavonoids from a Sponge-Derived Streptomyces sp. G248 in East Vietnam Sea.

Three new lavandulylated flavonoids, (2S,2''S)-6-lavandulyl-7,4'-dimethoxy-5,2'-dihydroxylflavanone (1), (2S,2''S)-6-lavandulyl-5,7,2',4'-tetrahydroxylflavanone (2), and (2''S)-5'-lavandulyl-2'-methoxy-2,4,4',6'-tetrahydroxylchalcone (3), along with seven known compounds 4-10 were isolated from culture broth of Streptomyces sp. G248. Their structures were established by spectroscopic data analysis, including 1D and 2D nuclear magnetic resonance (NMR), and high-resolution electrospray ionization mass spectrometry (HR-ESI-MS). The absolute configurations of 1-3 were resolved by comparison of their experimental and calculated electronic circular dichroism spectra. Compounds 1-3 exhibited remarkable antimicrobial activity. Whereas, two known compounds 4 and 5 exhibited inhibitory activity against Mycobacterium tuberculosis H37Rv with minimum inhibitory concentration (MIC) values of 6.0 µg/mL and 11.1 µg/mL, respectively.

Cytotoxic Alkaloids from Leaves of Pilea aff. martinii.

Two new phenanthroquinolizidine alkaloids (1: and 2: ) and a new piperidine derivative (3: ) were isolated from the leaves of Pilea aff. martinii together with 3 known alkaloids: julandine (4: ), cryptopleurine (5: ), and 1,3,6,6-tetramethyl-5,6,7,8-tetrahydro-isoquinolin-8-one (6: ). Their structures were determined by spectral data analyses including mass spectrometry and 2-dimensional nuclear magnetic resonance data. The absolute configurations of 1: -3: were established by comparison of their experimental circular dichroism data with the calculated electronic circular dichroism spectra. The isolated compounds were evaluated for their cytotoxicity against 4 cancer cell lines: KB (mouth epidermal carcinoma cells), HepG-2 (human liver hepatocellular carcinoma cells), LU-1 (human lung adenocarcinoma cells), and MCF-7 (human breast cancer cells). The new phenanthroquinolizidine pileamartine D (2: ) showed strong and selective proliferation inhibition toward KB and HepG-2 cells with IC50 values of 25 and 27 nM, respectively. Pileamartine C (1: ), julandine (4: ), and cryptopleurine (5: ) exhibited cytotoxicity against 4 tested cancer cell lines with IC50 values less than 1 µM.

New dianthramide and cinnamic ester glucosides from the roots of Aconitum carmichaelii.

Four new compounds N-salicyl-3-hydroxyanthranilic acid methyl ester (1), N-(2'-dehydroxysalicyl)-3-hydroxyanthranilic acid methyl ester (2), methyl-4-ß-D-allopyranosyl-ferulate (3), and methyl-4-ß-D-gulopyranosyl-cinnamate (4), along with six known compounds (5-10), were isolated from the roots of Aconitum carmichelii Debx. Their structures were elucidated on the basis of spectral data analysis, including 1D, 2D-NMR, and HR-ESI-MS. Compounds 1 and 2 showed the inhibition of nitric oxide (NO) production with IC50 values of 9.13 and 19.94 µM, respectively.

Antimicrobial metabolites from a marine-derived Actinomycete Streptomyces sp. G278.

Analysis of an antimicrobial extract prepared from culture broth of the marine-derived actinomycete Streptomyces sp. G278 led to the isolation of ten compounds, 1-10. Two compounds, 2,5-Bis(5-tert-butyl-2-benzoxazolyl)thiophene (1), and 3-hydroxyl-2-methylpyridine (2) were isolated from a natural source for the first time. The structures of the isolated compounds were established by their spectral data analysis, including mass spectrometry, 1D-NMR, 2D-NMR, and X-ray crystallographic analysis in case of compound 3. All isolated compounds were evaluated for their antimicrobial activity against a panel of clinically significant microorganisms. Compounds 1 and 3 selectively inhibited Enterococcus faecalis (MIC: 256 µg/mL). Compound 2 was found to have antibacterial and antifungal activity against Escherichia coli (MIC: 64 µg/mL), Salmonella enterica (MIC: 256 µg/mL), Staphylococcus aureus (MIC: 256 µg/mL), Enterococcus faecalis (MIC: 256 µg/mL), and Candida albicans (MIC: 64 µg/mL). Except for compounds 9 and 10, the other known metabolites (4-8) also exhibited antimicrobial activity.

New 9α-Hydroxy-5α,6α-epoxyhydroxysterols from the Vietnamese Marine Sponge Ircinia echinata.

Chemical investigation of the methanol extract of the Vietnamese marine sponge Ircinia echinata led to the isolation of six new 9α-hydroxy-5α,6α-epoxysterols: 5α,6α-epoxycholesta-7,22(E)-dien-3ß,9α-diol (1), 5α,6α-epoxycholesta-7,24(28)-dien-3ß,9α-diol (2), (24R)-5α,6α-epoxy-24-ethyl-cholesta-7-en-3ß,9α-diol (3), 5α,6α-epoxycholesta-7-en-3ß,9α-diol (4), (24S)-5α,6α-epoxyergosta-7,22-dien-3ß,9α-diol (5), and (24R)-5α,6α-epoxy-24-methyl-cholesta-7-en-3ß,9α-diol (6) along with the known 5α-6α-epoxysterols: 5α,6α-epoxystigmasta-7-en-3ß-ol (7), 5α,6α-epoxystigmasta-7,22-dien-3ß-ol (8), and 5α,6α-epoxyergosta-7-en-3ß-ol (9). Their structures and their configurations were established on the basis of high resolution mass spectra and extensive 1D and 2D NMR spectroscopic data and by comparison with the literature. Their cytotoxic activity, evaluated against three human cancer cell lines, MCF-7, Hep-G2 and LU-1, revealed that only compounds 3 and 4 exhibited significant antiproliferative activity and compound 3 showed a selective inhibition towards the MCF-7 human breast cancer cells.

Two new linear acetogenins from the fruits of Goniothalamus gracilipes.

Two new linear acetogenins, gracilipin A (1) and methylsaccopetrin A (2) along with seven known compounds, saccopetrin A (3), 7,3',4'-trimethylquercetin (4), rhamnazin (5), casticin (6), isokanugin (7), melisimplexin (8) and 5-hydroxy-3,7-dimethoxy-3',4'-methylenedioxyflavone (9) were isolated from the fruits of Goniothalamus gracilipes Bân. Their structures were established by spectral analysis, such as mass spectrometry, 1D-NMR, 2D-NMR and circular dichroism (CD). Compounds 1 and 3 showed cytotoxic activity against KB cell line with IC50 values of 14.6 and 15.3 µM, respectively.

Pregnane steroids from the Vietnamese octocoral Carijoa riisei.

Six pregnane steroids including one new compound namely 15ß-hydroxypregna-4,20-dien-3-one (1), were isolated and structurally elucidated from the octocoral Carijoa riisei. The cytotoxic activity against a panel of eight human cancer cell lines of isolated compounds was also evaluated by SRB method. As the results, 18-acetoxypregna-1,4,20-trien-3-one (5) showed significant cytotoxicity against all the tested cell lines with the IC50 values from 22.29 ± 1.47 to 48.73 ± 3.93 µM, whereas 15ß-acetoxypregna-1,4,20-trien-3-one (3) and 20R-acetoxypregna-1,4-dien-3-one (6) only exhibited weak effect on KB cell line with IC50 values of 93.62 ± 7.32 and 71.38 ± 5.45 µM, respectively.

Cytotoxic steroid derivatives from the Vietnamese soft coral Sinularia brassica.

Using various chromatographic separations, six ergostane-type steroids, including one new compound sinubrassione (1), and two pregnene-type steroid glycosides, including one new compound sinubrassioside (7), were isolated from methanol extract of the Vietnamese soft coral Sinularia brassica. The structure elucidation was confirmed by spectroscopic methods including 1D, 2D NMR and HR-ESI-MS. The cytotoxic activities of all the isolated compounds against three human cancer cell lines were also evaluated using MTT-based colorimetric assays.

Cytotoxic dammarane-type triterpenoids from the leaves of Viburnum sambucinum.

Four new dammarane-type triterpenoids (1-4) and twelve known compounds (5-16) were isolated from the leaves of Viburnum sambucinum Reinw. ex Blume. Their structures were determined by spectral data analysis, including MS and 2D NMR. Cytotoxic activity evaluation in vitro against four cancer cell lines (KB, LU-1, HepG2 and MCF7) suggested that the octanor-dammarane derivatives were the main cytotoxic components of the leaves of V. sambucinum.

Design, synthesis and cytotoxicity of bengamide analogues and their epimers.

Starting from d-glycero-d-gulo-heptonic acid γ-lactone and amino acids, a number of diastereoisomeric bengamide analogues were synthesized. Optimization of the reaction conditions revealed that microwave irradiation assistance is a powerful method for the preparation of aminolactams, as well as for the coupling reactions of the lactone 5 with aminolactams. Cytotoxic activity evaluation against six cancer cell lines (KB, HepG2, LU1, MCF7, HL60, and Hela) demonstrated that the configuration of C-2' seems to be critical for the cytotoxic activity of compounds 8b (2'R) and 8a (2'S). Additionally, comparison of cytotoxicity of the protected acetonide compounds with that of their corresponding deprotected bengamide analogues suggested that the flexibility of the ketide side chain should be required for their cytotoxic activity.

Two new sesquiterpenes from the fruits of Fissistigma villosissimum.

Two new sesquiterpenes, namely fissistinone (1) and fissistinol (2), along with ten known compounds (3-12), were isolated from the fruits of Fissistigma villosissimum. Their structures were elucidated on the basis of spectral data analysis, including one-dimensional (1D), two-dimensional (2D)-nuclear magnetic resonance (NMR), and high-resolution-electrospray ionization-mass spectrometry (HR-ESI-MS). Compounds 1-8 were evaluated for their cytotoxic activities against KB cell line; however, all these compounds did not show cytotoxic activity.

Secondary Metabolites from an Actinomycete from Vietnam's East Sea.

Analysis of an antimicrobial extract prepared from culture broth of the marine-derived actinomycete Nocardiopsis sp. (strain G057) led to the isolation of twelve compounds, 1-12. Compound 1 (2-[(2R-hydroxypropanoyl)amino]benzamide) was found to be a new enantiomeric isomer while compounds 2 (3-acetyl-4-hydroxycinnoline) and 3 (3,3'-bis-indole) were isolated from a natural source for the first time. The structures of 1-12 were determined by analyses of MS and 2D NMR data. All compounds were evaluated for their antimicrobial activity against a panel of clinically significant microorganisms. Compound 1 selectively inhibited Escherichia coli (MIC: 16 µg/mL). Compounds 2 and 3 exhibited antimicrobial activity against several strains of both Gram-positive and Gram-negative bacteria, and the yeast Candida albicans. Cytotoxic evaluation of compounds 1-3 against four cancer cell lines (KB, LU-1, HepG-2 and MCF-7) indicated that compound 3 produced a weak inhibition against KB and LU cell lines. Two remaining compounds, 1 and 2 were not cytotoxic, even at the concentration of 128 µg/mL.