Cytotoxic and antimalarial azaphilones from Chaetomium longirostre

Four new azaphilones named longirostrerones A-D (1-4) and three known sterols, ergosteryl palmitate, ergosterol, and ergosterol peroxide, have been isolated from ethyl acetate extract of the fungus Chaetomium longirostre. These structures were determined by 1D and 2D NMR, IR, UV, MS, and CD spectroscopy. Compounds 1-4 exhibited strong cytotoxicity against KB cancer cell lines (IC(50) 0.23-6.38 μM), while only 1 showed potent cytotoxicity against MCF7 and NCI-H187 cell lines (IC50 0.24 and 3.08 μM, respectively). In addition, 1-3 showed antimalarial activity against Plasmodium falciparum (IC50 0.62-3.73 μM).     

Marinoquinolines A-F, pyrroloquinolines from Ohtaekwangia kribbensis (Bacteroidetes)

Marinoquinoline A (1) was isolated from the gliding bacterium Ohtaekwangia kribbensis together with the novel marinoquinolines B-F (2-6). Their structures were elucidated from NMR and HRESIMS data. The pyrroloquinolines showed weak antibacterial and antifungal activities and moderate cytotoxicity against four growing mammalian cell lines with IC(50) values ranging from 0.3 to 8.0 μg/mL. In a screening against tropical parasites marinoquinolines A-F (1-6) showed activity against Plasmodium falciparum K1 with IC(50) values between 1.7 and 15 μM.     

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.     

Anti-inflammatory and cytotoxic neoflavonoids and benzofurans from Pterocarpus santalinus

Five new benzofurans, pterolinuses A-E (1-5), six new neoflavonoids, pterolinuses F-J (8-13), and five known compounds (6, 7, 14-16) were isolated from an extract of Pterocarpus santalinus heartwood. All new structures were elucidated by spectroscopic methods, and configurations were confirmed by CD spectral data and optical rotation values. The isolates were evaluated for anti-inflammatory and cytotoxic activities. Six compounds (1, 2, 4, 6, 7, and 15) showed significant inhibition in at least one anti-inflammatory assay. Compound 2 showed the best selective effect against superoxide anion generation in human neutrophils with, an IC50 value of 0.19 μg/mL, and was 6.2-fold more potent than the positive control LY294002. Compound 14 showed the highest cytotoxicity against Ca9-22 cancer cells, with an IC50 value of 0.46 μg/mL.     

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.     

Antimalarial activity of extract and norbergenin derivatives from the stem bark of Diospyros sanza-minika A. Chevalier (Ebenaceae)

The methanol extract from the stem bark of Diospyros sanza-minika as well as five norbergenin derivatives isolated from this crude extract were evaluated for their in vitro activity against Plasmodium falciparum K1 and cytotoxicity on MRC-5 cells. 4-O-(3'-methylgalloyl)norbergenin was found to be the most potent compound (IC(50) 0.6 μg/mL; CC(50) 24.7 μg/mL), followed by 4-O-galloylnorbergenin (IC(50) 3.9 μg/mL; CC(50) > 64 μg/mL) and 11-O-p-hydroxy-benzoyl-norbergenin (IC(50) 4.9 μg/mL; CC(50) > 64 μg/mL). Norbergenin and 4-O-syringoylnorbergenin were inactive (IC(50) > 32 μg/mL; CC(50) > 64 μg/mL). The antimalarial activity of the pure constituents and of the methanol extract from the stem bark of Diospyros sanza-minika is reported for the first time. The results provide interesting baseline information for the potential use of the crude extract well as some of the isolated compounds in the search for novel antimalarial compounds.     

Bioactive carbazole alkaloids from Clausena wallichii roots

Four new carbazole alkaloids, clausenawallines C-F (1-4), along with 18 known compounds (5-22) were isolated from the roots of Clausena wallichii. Compounds 3, 9, and 22 exhibited significant antibacterial activity against methicillin-resistant Staphylococcus aureus SK1 (MRSA SK1) and Staph. aureus TISTR 1466 with MIC values in the range 4-16 μg/mL, whereas compound 4 showed the highest cytotoxicity against oral cavity cancer (KB) and small-cell lung cancer (NCI-H187) with IC(50) values of 10.2 and 4.5 μM, respectively.     

Cytotoxic norsesquiterpene peroxides from the endophytic fungus Talaromyces flavus isolated from the mangrove plant Sonneratia apetala

Four new norsesquiterpene peroxides, named talaperoxides A-D (1-4), as well as one known analogue, steperoxide B (5, or merulin A), have been isolated from a mangrove endophytic fungus, Talaromyces flavus. Their structures were elucidated mainly by 1D and 2D NMR. Structures of 1, 2, and 5 were further confirmed by single-crystal X-ray diffraction, and their absolute configurations were also determined using copper radiation. Cytotoxic activities of compounds 1-5 were evaluated in vitro against human cancer cell lines MCF-7, MDA-MB-435, HepG2, HeLa, and PC-3. Compounds 2 and 4 showed cytotoxicity against the five human cancer cell lines with IC50 values between 0.70 and 2.78 μg/mL.     

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.     

7-Nor-ergosterolide, a pentalactone-containing norsteroid and related steroids from the marine-derived endophytic Aspergillus ochraceus EN-31

7-Nor-ergosterolide (1), a rare 7-norsteroid with an unusual pentalactone B-ring system, and two new steroid derivatives, 3β,11α-dihydroxyergosta-8,24(28)-dien-7-one (2) and 3β-hydroxyergosta-8,24(28)-dien-7-one (3), were characterized from the culture extract of Aspergillus ochraceus EN-31, an endophytic fungus isolated from the marine brown alga Sargassum kjellmanianum. In addition, nine known related steroids were isolated and identified. The structures of these compounds were established on the basis of extensive spectroscopic analysis. The absolute configuration of the new steroids (1-3) was determined by application of the modified Mosher's method. Compound 1, which represents the first example of a 7-nor-ergosteroid possessing a pentalactone B-ring system in a naturally occurring steroid, displayed cytotoxicity against NCI-H460, SMMC-7721, and SW1990 cell lines with IC(50) values of 5.0, 7.0, and 28.0 μg/mL, respectively. Compound 2 also displayed cytotoxicity against the SMMC-7721 cell line with an IC(50) value of 28.0 μg/mL.     

Cytotoxic diterpenoids from Sapium insigne

Chemical investigation into the twigs and leaves of Sapium insigne afforded seven new diterpenoids, sapinsignoids A-G (1-7), together with 10 known diterpenoids. The structures of 1-7 were assigned on the basis of detailed spectroscopic analysis and chemical degradation. Compounds 1-4 exhibited significant cytotoxicity against the A-549 tumor cell line (IC(50) 0.2-1.8 μM), while compounds 1-3 showed moderate cytotoxicity against the HL-60 cell line (IC(50) 2.7-6.5 μM).     

Hippolides A-H, acyclic manoalide derivatives from the marine sponge Hippospongia lachne

Eight new acyclic manoalide-related sesterterpenes, hippolides A-H (1-8), together with two known manoalide derivatives, (6E)-neomanoalide (9) and (6Z)-neomanoalide (10), were isolated from the South China Sea sponge Hippospongia lachne. The absolute configurations of 1-8 were established by the modified Mosher's method and CD data. Compound 1 exhibited cytotoxicity against A549, HeLa, and HCT-116 cell lines with IC50 values of 5.22×10(-2), 4.80×10(-2), and 9.78 μM, respectively. Compound 1 also showed moderate PTP1B inhibitory activitiy with an IC50 value of 23.81 μM, and compound 2 showed moderate cytotoxicity against the HCT-116 cell line and PTP1B inhibitory activity with IC50 values of 35.13 and 39.67 μM, respectively. In addition, compounds 1 and 5 showed weak anti-inflammatory activity, with IC50 values of 61.97 and 40.35 μM for PKCγ and PKCα, respectively.     

Macrophyllionium and macrophyllines A and B, oxindole alkaloids from Uncaria macrophylla

An unusual oxindole alkaloid inner salt, macrophyllionium (1), and a pair of new tetracyclic oxindole alkaloids, macrophyllines A (2) and B (3), together with six known alkaloids, were isolated from the aerial parts of Uncaria macrophylla. Corynantheidine (8) exhibited moderate cytotoxicity against HL-60 and SW480 cells with IC(50) values of 13.96 and 23.28 μM, respectively. Dihydrocorynantheine (9) exhibited significant vasodilating activity against phenylephrine-induced contraction in rat thoracic aorta rings (IC(50) = 6.73 μg/mL). In addition, compounds 2, 6, and 9 showed weak inhibitory action on KCl-induced contraction.     

Indiosides G-K: steroidal glycosides with cytotoxic and anti-inflammatory activities from Solanum violaceum

Five new steroidal glycosides (1-5) and nine known compounds were isolated from Solanum violaceum. Indiosides G (1) and H (2) are spirostene saponins with an iso-type F ring, indioside I (3) is a spirostane saponin, and indiosides J (4) and K (5) are unusual furostanol saponins with a deformed F ring. These structures represent rare naturally occurring steroidal skeletons. The structures of the new compounds were elucidated using 1D and 2D spectroscopic techniques and acid hydrolysis. Compounds 2, 3, and 7-9 exhibited cytotoxic activity against six human cancer cell lines (HepG2, Hep3B, A549, Ca9-22, MDA-MB-231, and MCF-7) with IC(50) values of 1.83-8.04 μg/mL. Steroidal saponins 3, 8, and 9 showed inhibitory effects on superoxide anion generation with IC(50) values of 2.84 ± 0.18, 0.62 ± 0.03, and 1.62 ± 0.59 μg/mL, respectively. Saponins 8 and 9 also inhibited elastase release with IC(50) values of 111.05 ± 7.37 and 4.04 ± 0.51 μg/mL, respectively. Structure-activity relationship correlations of these compounds with respect to cytotoxic and anti-inflammatory effects are discussed.     

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.     

Trigoflavidols A-C, degraded diterpenoids with antimicrobial activity, from Trigonostemon flavidus

Trigoflavidols A (1) and B (2), tetranorditerpenoid dimers possessing a rearrangement skeleton with a spiroketal core moiety, and trigoflavidol C (3), a hexanorditerpenoid, have been isolated from Trigonostemon flavidus along with two known compounds. Compounds 1 and 2 showed moderate antimicrobial activities (MIC values: 3.12-6.25 μg/mL) against Staphylococcus aureus, 8(#)MRSA, and 82(#)MRSA, and 1, 2, and 5 showed weak activities (IC(50) values: 3.75-28.99 μM) against various human tumor cell lines.     

Two new cytotoxic linderazulenes from a deep-sea gorgonian of the genus Paramuricea

The known compound linderazulene (1) and two new linderazulenes (2, 3) were isolated from a deep-sea gorgonian Paramuricea sp. The structures of 2 and 3 were determined through spectroscopic methods. Compounds 1-3 show moderate in vitro cytotoxicity against the P388 murine leukemia cell line with IC(50)'s of 18.8, 2.7, and 15.6 microg/mL, respectively. Compound 2 showed moderate activity against the PANC-1 pancreatic cell line with an IC(50) of 18.7 microg/mL.     

Antimalarial, cytotoxic, and antifungal alkaloids from Duguetia hadrantha

Bioassay-guided isolation of Duguetia hadrantha yielded two new 4,5-dioxo-1-azaaporphinoids, hadranthine A (1) and hadranthine B (2), together with the known alkaloids imbiline-1 (3), sampangine (4), and 3-methoxysampangine (5), whose structures were determined primarily from 2D-NMR 1H-13C HMBC, and 1H-15N HMBC experiments. This is the first report of the co-occurrence of the copyrine alkaloids 4 and 5, as well as the first report of either copyrine or imbiline type alkaloids from a Duguetia species. Compounds 1, 4, and 5 demonstrated in vitro antimalarial activity against Plasmodium falciparum (W-2 clone), while 2 was inactive. Instead, 2 showed in vitro cytotoxicity to selected human cancer cell lines (IC50 = 3-6 microg/mL against SK-MEL, KB, BT-549, and SK-OV-3), and 4 was also cytotoxic to human malignant melanoma (IC50 = 0.37 microg/mL). Sampangine (4) also inhibited cell aggregation with a MIC value of <0.15 microg/mL, while 3-methoxysampangine (5) was only weakly active.     

Diarylpropanes and an arylpropyl quinone from Combretum griffithii

Three new diarylpropanes (1-3), a new arylpropyl quinone (4), and the known 1-(2-hydroxy-4-methoxyphenyl)-3-(4-hydroxy-3-methoxyphenyl)propane (5) were isolated from a methanol extract of stems of Combretum griffithii. Their structures were elucidated by spectroscopic methods. Compounds 1, 2, 4, and 5 showed cytotoxicity against one or more cancer cell lines (KB, MCF7, and NCI-H187), and compound 5 exhibited activity against Mycobacterium tuberculosis (MIC 3.13 μg/mL).     

Claurailas A-D, cytotoxic carbazole alkaloids from the roots of Clausena harmandiana

Four new carbazole alkaloids, claurailas A-D (1-4), as well as 12 known carbazoles and three known coumarins were isolated from the roots of Clausena harmandiana. Heptaphylline (6) and 7-methoxyheptaphylline (7) showed strong cytotoxicity against NCI-H187 and KB cell lines with IC(50) values ranging from 1.3 to 2.7 μM. Compound 7 showed no cytotoxicity against Vero cells.