New bioactive prenylflavonoids and dibenzocycloheptene derivative from roots of Dendrolobium lanceolatum

Two new flavanones (1 and 2), a new flavan (3), and a new rare dibenzocycloheptene derivative (4) together with a known flavan, 4'-hydroxy-2' ',2' 'dimethyl-pyranoflavan (5), were isolated from the roots of Dendrolobium lanceolatum. Their structures were established on the basis of spectral evidence, and an X-ray analysis was performed to confirm the structure of 4. Compounds 1-3 exhibited antimalarial activity with IC50 values of 2.6, 3.3, and 3.1 microg/mL, respectively. Compounds 1-5 showed moderate antimycobacterial activity with MIC values of 6.3, 12.5, 25, 25, and 50 microg/mL, respectively. In addition, 1 showed strong cytotoxicity against cancer cell lines KB, BC, and NCI-H187 with IC50 values of 1.2, 1.6, and 0.6 microg/mL, respectively, while 2 showed moderate cytotoxicity against the NCI-H187 cell line with an IC50 value of 8.1 microg/ mL.     

Dehydrozingerone, chalcone, and isoeugenol analogues as in vitro anticancer agents

Twenty-eight compounds related to dehydrozingerone (1), isoeugenol (3), and 2-hydroxychalcone (4) were synthesized and evaluated in vitro against human tumor cell replication. Except for isoeugenol analogues 27-35, most compounds exhibited moderate or strong cytotoxic activity against KB, KB-VCR (a multidrug-resistant derivative), and A549 cell lines. In particular, chalcone 15 showed significant cytotoxic activity against the A549 cell line with an IC50 value of 0.6 microg/mL. Furthermore, dehydrozingerone analogue 11 and chalcones 16 and 17 showed significant and similar cytotoxic activity against both KB (IC50 values of 2.0, 1.0, and 2.0 microg/mL, respectively) and KB-VCR (IC50 values of 1.9, 1.0, and 2.0 microg/mL, respectively) cells, suggesting that they are not substrates for the P-glycoprotein drug efflux pump.     

Potent antiviral potamogetonyde and potamogetonol, new furanoid labdane diterpenes from Potamogeton malaianus

New furanoid labdane diterpenes, potamogetonyde (3) and potamogetonol (4), together with two known compounds, potamogetonin (1) and 15,16-epoxy-12-oxo-8(17),13(16),14-labdatrien-20,19-olide (2), were isolated from the CH(2)Cl(2) extract of Potamogeton malaianus. The chemical structures of 1-4 were elucidated by the analyses of their spectral data, mainly by 1D and 2D NMR techniques. Potamogetonyde (3) and potamogetonol (4) exhibited potent antiviral (HSV-1) activity with respective IC(50) values of 8 and 3 microg/mL. Compounds 1-4 possessed cytotoxicity toward insect cells (fall armyworm and mosquito larvae, IC(50) of 11-72 microg/mL). Furanoid diterpenes 3 and 4 also exhibited cytotoxicity against the Vero cell line with respective IC(50)'s of 31 and 28 microg/mL, while 1 and 2 were inactive at 50 microg/mL. Compounds 1-4 were inactive (at 20 microg/mL) against KB and BC cell lines and showed only weak antimycobacterial activity against Mycobacterium tuberculosis H37Ra with minimum inhibitory concentrations of 50-100 microg/mL.     

Lakoochins A and B, new antimycobacterial stilbene derivatives from Artocarpus lakoocha

Two new stilbene derivatives, lakoochins A (1) and B (2), were isolated from the roots of Artocarpus lakoocha. The structures of 1 and 2 were elucidated by analysis of their spectral data. Lakoochins A (1) and B (2) exhibited antimycobacterial activity with the respective MIC values of 12.5 and 50 microg/mL. While 1 was cytotoxic against the BC (breast cancer) cell line (IC(50) 6.1 microg/mL) but inactive (at 20 microg/mL) toward KB (nasopharyngeal carcinoma) cells, compound 2 possessed cytotoxicity against the BC and KB cell lines with IC(50) values of 3.1 and 6.1 microg/mL, respectively.     

Isolation and identification of cytotoxic compounds from the wood of Pinus resinosa

Methanol extracts of wood from Pinus resinosa were found to be selectively cytotoxic against human lung carcinoma cells, A549 (IC50 41 +/- 6 microg/mL), human colorectal adenocarcinoma cells, DLD-1 (IC50 47 +/- 4 microg/mL) in comparison with healthy cells, WS1 (IC50 130 +/- 11 microg/mL). Five known compounds were isolated and identified by 1H, 13C NMRspectroscopy and HR-ESI-MS mass spectrometry as, pinosylvin monomethyl ether (1), pinosylvin (2), pinosylvin dimethyl ether (3), pinobanksin (4) and (-)-norachelogenin (5). Compound 4 was isolated for the first time in P. resinosa. The cytotoxicity of compounds 1-5 was evaluated against A549, DLD-1 and WS1. Compound 1 exhibited the strongest cytotoxicity against both tumor cell lines and the healthy cell line with an IC50 of 25 +/- 4 microm for A549, 20 +/- 1 microm for DLD-1 and 34 +/- 3 microm for WS1.     

Bioactive compounds from Rhodiola rosea (Crassulaceae)

The methanol extract of the underground part of Rhodiola rosea was found to show inhibitory activity against Staphylococcus aureus. Bioactivity-guided fractionation of a 95% ethanol extract from the stems of R. rosea led to the isolation of five compounds: gossypetin-7-O-L-rhamnopyranoside (1), rhodioflavonoside (2), gallic acid (3), trans-p-hydroxycinnamic acid (4) and p-tyrosol (5). Their structures were elucidated by UV, IR, MS and NMR data, as well as by comparison with those of the literature. Compounds 1 and 2 were evaluated for their antibacterial and antiprostate cancer cell activities. Compounds 1 and 2 exhibited activity against Staphylococcus aureus with minimum inhibitory concentrations of 50 microg/mL and 100 microg/mL, respectively. Cytotoxicity studies of 1 and 2 also displayed activity against the prostate cancer cell line with IC(50) values of 50 microg/mL and 80 microg/mL, respectively.     

Cytotoxic and antioxidant activities of alkylated benzoquinones from Maesa lanceolata

The natural and semi-synthetic analogs of substituted 1,4-benzoquinones were evaluated for in vitro cytotoxic and antioxidant activities. Maesanin, dihydromaesanin, maesanin dimethyl ether and isomeric mixtures of 3-[(Z)-10'-pentadecenyl]-benzoquinone derivatives exhibited cytotoxic activity against HL-60 cell line (IC50 values 4.5, 2.2, 0.43 and 2.8 microg/mL, respectively), while it was found to be inactive against ROS (Reactive Oxygen Species) generation in HL-60. In contrast, the isomeric acylated benzoquinones with shorter alkyl substituents, namely, 2-acetoxy-5-hydoxy-6-methyl-3-tridecyl-1,4-benzoquinone and 2-hydoxy-5-acetoxy-6-methyl-3-tridecyl-1,4-benzoquinone showed most prominent antioxidant and antiproliferative effect on HL-60 (IC50 values 6.2 and 2.2 microg/mL, respectively), as well as cytotoxicities against SK-MEL, KB, BT-549 and SK-OV-3 carcinomas (IC50 values <1.1-4.2 microg/mL). All benzoquinones were found to be inactive against cell aggregation and cell adhesion assays, thus showing no effect on immune responses and inflammation.     

A cytotoxic sesquiterpene alkaloid from the South China Sea gorgonian Subergorgia suberosa

A new sesquiterpene alkaloid, 6-(9'-purine-6',8'-diolyl)-2beta-suberosanone (1), together with three known sesquiterpenes, suberosenol A (2), subergorgic acid (3), and subergorgiol (4), was isolated from the EtOH/CH2Cl2 extracts of the South China Sea gorgonian Subergorgia suberosa. The structure of 1 was determined through spectroscopic methods. Compound 1 showed moderate cytotoxicity against the human breast carcinoma MDA-MB-231 cell line with an IC50 of 8.87 microg/mL.     

Antiviral flavans from the leaves of Pithecellobium clypearia

Two new antiviral flavan derivatives were isolated from a methanol extract of leaves of Pithecellobium clypearia as guided by antiviral assays. The structures were characterized, by spectroscopic analyses, as 7-O-galloyltricetifavan (1) and 7,4'-di-O-galloyltricetifavan (2). Cytopathic effect (CPE) reduction assay showed that both compounds 1 and 2 possess antiviral activity against respiratory syncytial virus (RSV), with 50% inhibition concentration (IC(50)) values of 5 and 10 microg/mL, respectively; influenza A (H1N1) virus, with IC(50) values of 15.7 and 30 microg/mL; Coxsackie B3 (Cox B3) virus, with IC(50) values of 12.5 and 25 microg/mL, respectively; and Herpes simplex virus type 1 (HSV-1) with IC(50) values of 30 and 20 microg/mL, respectively. Cytotoxicity evaluation using the MTT assay showed that both compounds 1 and 2 were also moderately toxic to several cultured cell lines.     

Antiparasitic alkaloids from Psychotria klugii

Psychotria klugii yielded two new benzoquinolizidine alkaloids, klugine (1) and 7'-O-demethylisocephaeline (2), together with the previously known cephaeline (3), isocephaeline (4), and 7-O-methylipecoside (5). The structures and stereochemistry of 1 and 2 were determined by 1D and 2D NMR data and circular dichroism experiments. Cephaeline (3) demonstrated potent in vitro antileishmanial activity against Leishmania donavani (IC(50) 0.03 microg/mL) and was >20- and >5-fold more potent than pentamidine and amphotericin B, respectively, while klugine (1) (IC(50) 0.40 microg/mL) and isocephaeline (4) (IC(50) 0.45 microg/mL) were <13- and <15-fold less potent than 3. In addition, emetine (6) (IC(50) 0.03 microg/mL) was found to be as equally potent as 3, but was >12-fold more toxic than 3 against VERO cells (IC(50) 0.42 vs 5.3 microg/mL). Alkaloids 1 and 3 exhibited potent antimalarial activity against Plasmodium falciparum clones W2 and D6 (IC(50) 27.7-46.3 ng/mL). Compound 3 was cytotoxic to SK-MEL, KB, BT-549, and SK-OV-3 human cancer cells, while 1 was inactive.     

Cytotoxic diterpenoids from the soft coral Sarcophyton crassocaule

Five new cembrane diterpenoids, sarcrassins A-E (1-5) along with a known compound, emblide (6), have been isolated from the soft coral Sarcophyton crassocaule collected from the Bay of Sanya, Hainan Island, China. The structures of 1-5 were determined by spectroscopic methods including 1D and 2D NMR techniques. Their relative configurations were determined by NMR data and NOESY experiments. Compounds 2, 4, and 6 exhibited significant cytotoxic activities against KB cell lines with IC50 values of 5.0, 4.0, and 5.0 microg/mL, respectively, while compounds 1 and 5 showed moderate cytotoxicity toward KB cell lines with IC50 values of 19.0 and 13.0 microg/mL, respectively.     

In vitro antileishmanial and antimalarial activities of tetrahydrofuran lignans isolated from Nectandra megapotamica (Lauraceae)

Seven tetrahydrofuran lignans, isolated from Nectandra megapotamica (Lauraceae), were evaluated for their in vitro antileishmanial and antimalarial activities. Among the evaluated compounds, machilin-G (1a) and veraguensin (2a) showed the highest antileishmanial activities, displaying for both compounds an IC(50) value of 18 microg/mL and an IC(90) value of 36 microg/mL, while galgravin (1b), nectandrin-A (1c), nectandrin-B (1d), calopeptin (2b) and ganshisandrine (3) were inactive against Leishmania donovani. In the antimalarial assay against Plasmodium falciparum, it was observed that calopeptin (2b) displayed moderate activity, with IC(50) values of 3800 ng/mL (D6 clone) and 3900 ng/mL (W2 clone), while the lignans 1a-1d, 2a and 3 were inactive. In order to compare the effect on the parasites with toxicity to mammalian cells, the cytotoxic activity of the isolated compounds were evaluated against the Vero cells, showing that all evaluated tetrahydrofuran lignans exhibited no cytotoxicity at the maximum dose tested.     

Antimicrobial and antiparasitic (+)-trans-hexahydrodibenzopyrans and analogues from Machaerium multiflorum

Machaerium multiflorum yielded two additional new (+)-trans-hexahydrodibenzopyrans (HHDBP's), machaeriol C (1) and machaeriol D (2), and three new 5,6-seco-HHDBP's, machaeridiol A (3), machaeridiol B (4), and machaeridiol C (5). Their structures and stereochemistries were determined by 1D and 2D NMR data, including HMBC, NOESY, and circular dichroism experiments. Machaeriol C (1) demonstrated in vitro antibacterial activity against Staphylococcus aureus (IC(50) 0.65 microg/mL) and methicillin-resistant S. aureus (MRSA) (IC(50) 0.70 microg/mL), while its corresponding 5,6-seco-analogues machaeridiol A (3) and machaeridiol B (4) showed antibacterial activity against S. aureus and MRSA (IC(50) 1.0-2.6 microg/mL) and antifungal activity against Candida albicans (IC(50), 2.0-3.5 microg/mL). In addition, machaeridiol B (4) demonstrated antiparasitic activities against Plasmodium falciparum D6 and W2 clones and Leishmania donavani with IC(50) values of 0.64, 0.22, and 0.9 microg/mL, respectively.     

Cyclopentenones, scaffolds for organic syntheses produced by the endophytic fungus mitosporic dothideomycete sp. LRUB20

Two new natural products, 2-hydroxymethyl-3-methylcyclopent-2-enone (1) (synthetically known) and cis-2-hydroxymethyl-3-methylcyclopentanone (2), and a known compound, asterric acid (3), were isolated from the endophytic fungus mitosporic Dothideomycete sp. LRUB20, which was isolated from the stem of the Thai medicinal plant Leea rubra. Compound 2 was separated and identified in the form of its 2,4-dinitrophenylhydrazone derivative (5). Compounds 1, 3, and hydrazone 5 exhibited mild antimycobacterial activity, both with MIC values of 200 microg/mL. Compounds 1, 3, and 4 were inactive (at 50 microg/mL) toward Vero, KB, NCI-H187, and BC cell lines. Hydrazone 5 showed only mild cytotoxicity against the Vero cell line with an IC(50) value of 21.7 microg/mL; however, it was inactive toward KB, NCI-H187, and BC cell lines. Endophytic fungi may be a source for the production of building blocks for organic syntheses.     

Cytotoxic diarylheptanoids from the roots of Juglans mandshurica

A new (2) and three known diarylheptanoids (1, 3, and 4), along with one known sesquiterpenoid (5), were isolated from the roots of Juglans mandshurica, and their structures were elucidated on the basis of spectroscopic studies. Four of these compounds (2-5) exhibited moderate cytotoxicities against human colon carcinoma and human lung carcinoma cell lines with IC(50)'s ranging from 2 to 25 microg/mL.     

New antimycobacterial and antimalarial 8,9-secokaurane diterpenes from Croton kongensis

Two new 8,9-secokaurane diterpenes, ent-8,9-seco-7alpha,11beta-diacetoxykaura-8(14),16-dien-9,15-dione (1) and ent-8,9-seco-8,14-epoxy-7alpha-hydroxy-11beta-acetoxy-16-kauren-9,15-dione (2), together with two known compounds, ent-8,9-seco-7alpha-hydroxy-11beta-acetoxykaura-8(14),16-dien-9,15-dione (3) and ent-7beta-hydroxy-15-oxokaur-16-en-18-yl acetate, were isolated from Croton kongensis. This is the first report on the presence of 8,9-secokauranes in the plant genus Croton. Diterpenes 1-3 exhibited antimycobacterial activity with minimum inhibitory concentrations (MICs) of 25.0, 6.25, and 6.25 microg/mL, respectively, and possessed antimalarial activity with IC(50) ranges of 1.0-2.8 microg/mL. They also demonstrated comparable cytotoxicity toward the Vero (IC(50) ranged from 0.9 to 3.2 microg/mL), KB (IC(50) from 1.2 to 13.8 microg/mL), and BC cell lines (IC(50) from 1.1 to 2.2 microg/mL, except for compound 1, which was inactive against BC cells).     

A new antimalarial quassinoid from Simaba orinocensis

A new antimalarial quassinoid, namely, orinocinolide (1), was isolated from the root bark of Simaba orinocensis, together with the previously reported simalikalactone D (2). The structure of 1 was determined primarily from 1D and 2D NMR analysis, as well as by chemical derivatization. Compound 1 was found to be as equally potent as 2 against Plasmodium falciparum clones D6 and W2 (IC(50) 3.27 and 8.53 ng/mL vs 3.0 and 3.67 ng/mL, respectively), but was 4- and 28-fold less toxic than 2 against VERO cells (IC(50) 10 vs 2.3 microg/mL) and HL-60 (IC(50) 0.7 vs 0.025 microg/mL), respectively. In addition, 2 was >46- and >31-fold more potent than pentamidine and amphotericin B (IC(50) 0.035 vs 1.6 and 1.1 microg/mL) against Leishmania donovani, while 1 was inactive. Orinocinolide (1) inhibited growth of human cancer cells SK-MEL, KB, BT-549, and SK-OV-3, but was less potent than 2 (IC(50) 0.8-1.9 vs 0.3-1.0 microg/mL) against these cells.     

Antiprotozoal activities of heterocyclic-substituted xanthones from the marine-derived fungus Chaetomium sp

Investigations of the marine-derived fungus Chaetomium sp. led to the isolation of the new natural products chaetoxanthones A, B, and C (1-3). Compounds 1 and 2 are substituted with a dioxane/tetrahydropyran moiety rarely found in natural products. Compound 3 was identified as a chlorinated xanthone substituted with a tetrahydropyran ring. The configurational analysis of these compounds employed CD spectroscopy, modified Mosher's method, and selective NOE gradient measurements. Compound 2 showed selective activity against Plasmodium falciparum with an IC50 value of 0.5 microg/mL without being cytotoxic toward cultured eukaryotic cells. Compound 3 displayed a moderate activity against Trypanosoma cruzi with an IC50 value of 1.5 microg/mL.     

Bioactive dibenzylbutyrolactone and dibenzylbutanediol lignans from Peperomia duclouxii

Six new dibenzylbutyrolactone (6-11) and two new dibenzylbutanediol lignans (12, 13) were obtained from Peperomia duclouxii. The structures were elucidated mainly by the analysis of NMR and MS data. The anticancer activity against a normal (WI-38) and a simian virus 40-transformed human lung fibroblast cell (VA-13) and a hepatoma G2 cell (HepG2) and the MDR reversal activity of the isolated compounds were examined. Compound 7 showed moderate inhibitory activity against VA-13 and HepG2 with IC(50) values of 23.2 and 26.4 microM, respectively. Compound 2 inhibited the growth of HepG2 cells with an IC(50) of 42.8 microM. Compounds 2 and 13 exhibited stronger MDR reversal activity than verapamil, at 25 and 2.5 microg/mL, respectively, and 4, 5, and 7 showed comparable activity with verapamil, at 25, 25, and 2.5 microg/mL, respectively.     

Cytotoxic diterpenoids from the soft coral Sinularia microclavata

The soft coral Sinularia microclavata collected from the bay of Sanya, Hainan Island, China, yielded a new diterpenoid, microclavatin (1), and a known cembranolide, capillolide (2). The structure of compound 1 was determined on the basis of spectroscopic methods and X-ray single-crystal diffraction analysis. Microclavatin (1) showed cytotoxic activities against tumor cell lines KB and MCF with IC50 values of 5.0 and 20.0 microg/mL, respectively, and capillolide (2) showed potent cytotoxic activity against tumor cell lines (A-549) with an IC50 value of 0.5 microg/mL.