We screened more than 60 Malaysian plants against two species of insects and found that Melicope subunifoliolata (Stapf) T.G. Hartley (Rutaceae) showed strong feeding deterrent activity against Sitophilus zeamais Motsch. (Curculionidae) and very good larvicidal activity against Aedes aegypti L. (Diptera). One anti-insect compound, meliternatin (3,5-dimethoxy-3',4',6,7-bismethylendioxyflavone) (6) and six other minor polyoxygenated flavones were isolated from M. subunifoliolata.
Leaf extracts of Melicope lunu-ankenda were chemically studied and found to contain mixtures of hydrocarbons and squalene, fatty acids and esters. A geranylated coumaric acid was isolated as the major compound. The crude dichloromethane and methanol extracts of the leaves were found to be strongly larvicidal with LC50 values below 20 microg mL(-1). This is a first isolation of p-O-geranylcoumaric acid from this plant.
The antioxidant, radical-scavenging, anti-inflammatory, cytotoxic and antibacterial activities of methanolic extracts of seven Hedyotisspecies were investigated. The antioxidant activity was evaluated by the ferric thiocyanate (FTC) and thiobarbituric acid (TBA) methods while the radical scavenging activity was measured by the 1,1-diphenyl-2-picrylhydrazyl (DPPH) method. The anti-inflammatory activity related to NO inhibition of the plant extracts was measured by the Griess assay while cytotoxicity were measured by the MTT assay against CEM-SS cell line. The antibacterial bioassay (against 4 bacteria, i.e. Bacillus subtilis B28 (mutant), Bacillus subtilis B29 (wild-type), Pseudomonas aeruginosa UI 60690 and methicillin resistant Staphylococcus aureus, (MRSA) was also carried out using the disc-diffusion method. All tested extracts exhibited very strong antioxidant properties when compared to Vitamin E (alpha-tocopherol) with percent inhibition of 89-98% in the FTC and 60-95% in the TBA assays. In the DPPH method, H. herbacea exhibited the strongest radical scavenging activity with an IC50 value of 32 microg/ml. The results from the Griess assay showed that the tested extracts are weak inhibitors of NO synthase. However, all tested extracts exhibited moderate cytotoxic properties against CEM-SS cell line giving CD50 values in the range of 21-41 microg/ml. In the antibacterial bioassay, the stems and the roots of H. capitellata showed moderate activity against the 4 tested bacteria while the leaves showed moderate activity towards B. subtilis B28, MRSA and P. aeruginosa only. The roots of H. dichotoma showed strong antibacterial activity against all 4 bacteria. All other extracts did not exhibit any antibacterial activity.
Four new furanoanthraquinones, 2-hydroxymethyl-3,4-[2'-(1-hydroxy-1-methylethyl)-dihydrofurano]-8-hydroxyanthraquinone, 2-hydroxymethyl-3,4-[1'-hydroxy-2'-(1-hydroxy-1-methylethyl)-dihydrofurano]-8-hydroxyanthraquinone, 2-hydroxymethyl-3,4-[2'-1-hydroxy-1-methylethyl)-dihydrofurano]anthraquinone and 2-methyl-3,4-[2'-(1-hydroxy-1-methylethyl)-dihydrofurano] anthraquinone or capitellataquinone A-D and four known anthraquinones, rubiadin, anthragallol 2-methyl ether, alizarin 1-methyl ether and digiferruginol, together with scopoletin were isolated from the stems of Hedyotis capitellata Wall (Rubiaceae). Lucidin-3-O-beta-glucoside was isolated from the roots of the plant. Characterization of the new compounds was carried out by extensive NMR studies using FGCOSY, FGHMQC, FGHMBC and DEPT-135 in addition to other spectroscopic methods.
A new labdane diterpene glucoside, curcumanggoside (1), together with nine known compounds, including labda-8(17),12-diene-15,16-dial (2), calcaratarin A (3), zerumin B (4), scopoletin, demethoxycurcumin, bisdemethoxycurcumin, 1,7-bis(4-hydroxyphenyl)-1,4,6-heptatrien-3-one, curcumin, and p-hydroxycinnamic acid, have been isolated from the rhizomes of Curcuma mangga. Their structures were determined using a combination of 1D (1H NMR, 13C NMR, DEPT) and 2D (COSY, HSQC, HMBC) NMR techniques. All diarylheptanoids and scopoletin showed significant antioxidant activity. Zerumin B, demethoxycurcumin, bisdemethoxycurcumin, and curcumin also exhibited cytotoxic activity against a panel of five human tumor cell lines.
The leaves of Melicope ptelefolia (Rutaceae) afforded a new acetophenone named 2,4,6-trihydroxy-3-geranylacetophenone. The structure of the compound was established by mass and NMR spectroscopy.
Some chalcones, such as hydroxychalcones have been reported previously to inhibit major pro-inflammatory mediators such as nitric oxide (NO), prostaglandin E(2) (PGE(2)), tumor necrosis factor-alpha (TNF-alpha) and reactive oxygen species production by suppressing inducible enzyme expression via inhibition of the mitogen-activated protein kinase (MAPK) pathway and nuclear translocation of critical transcription factors. In this report, the effects of cardamonin (2',4'-dihydroxy-6'-methoxychalcone), a chalcone that we have previously isolated from Alpinia rafflesiana, was evaluated upon two cellular systems that are repeatedly used in the analysis of anti-inflammatory bioactive compounds namely RAW 264.7 cells and whole blood. Cardamonin inhibited NO and PGE(2) production from lipopolysaccharide- and interferon-gamma-induced RAW cells and whole blood with IC(50) values of 11.4 microM and 26.8 microM, respectively. Analysis of thromboxane B(2) (TxB(2)) secretion from whole blood either stimulated via the COX-1 or COX-2 pathway revealed that cardamonin inhibits the generation of TxB(2) via both pathways with IC(50) values of 2.9 and 1.1 microM, respectively. Analysis of IC(50) ratios determined that cardamonin was more COX-2 selective in its inhibition of TxB(2) with a ratio of 0.39. Cardamonin also inhibited the generation of intracellular reactive oxygen species and secretion of TNF-alpha from RAW 264.7 cells in a dose responsive manner with IC(50) values of 12.8 microM and 4.6 microM, respectively. However, cardamonin was a moderate inhibitor of lipoxygenase activity when tested in an enzymatic assay system, in which not a single concentration tested was able to cause an inhibition of more than 50%. Our results suggest that cardamonin acts upon major pro-inflammatory mediators in a similar fashion as described by previous work on other closely related synthetic hydroxychalcones and strengthens the conclusion of the importance of the methoxyl moiety substitution on the 4' or 6' locations of the A benzene ring.
A peptide with the sequence CTLTTKLYC has previously been identified to inhibit the propagation of Newcastle disease virus (NDV) in embryonated chicken eggs and tissue culture. NDV has been classified into two main groups: the velogenic group, and mesogenic with lentogenic strains as the other group based on its dissociation constants. In this study the peptide, CTLTTKLYC, displayed on the pIII protein of a filamentous M13 phage was synthesized and mutated in order to identify the amino acid residues involved in the interactions with NDV. Mutations of C1 and K6 to A1 and A6 did not affect the binding significantly, but substitution of Y8 with A8 dramatically reduced the interaction. This suggests that Y8 plays an important role in the peptide-virus interaction. The three-dimensional structure of the peptide was determined using circular dichroism (CD), nuclear magnetic resonance (NMR), and molecular modeling. The peptide exhibited two possible conformers. One that consists of consecutive beta-turns around T2-L3-T4-T5 and K6-L7-Y8-C9. The other conformer exhibited a beta-hairpin bend type of structure with a bend around L3-T4-T5-K6.
Nine derivatives of three natural diarylheptanoids, curcumin, demethoxycurcumin and bisdemethoxycurcumin, were prepared. Their antioxidant, free radical scavenging, nitric oxide (NO) inhibitory and cytotoxic activities were evaluated and compared with those of the respective natural compounds. Curcumin (1), demethoxycurcumin (2), demethyldemethoxy-curcumin (C3), diacetyldemethoxycurcumin (AC2) and triacetyldemethylcurcumin (AC5) exhibited higher antioxidant activity than quercetin while products from demethylation of 1 and 2 exhibited higher free radical scavenging activity. Compounds AC2 and AC5 were found to be most active in inhibiting breast cancer cells (MCF-7) proliferation with IC50 values of 6.7 and 3.6 microM, respectively. The activity of AC2 is almost doubled and of AC5 almost tripled as compared to curcumin. Their selectivity towards different cell lines is also more noticeable. Compounds AC2 and AC5 also showed increased activity against a human prostate cancer cell line (DU-145) and non-small lung cancer cell line (NCI-H460) with IC50 values of 20.4, 16.3 and 18.3, 10.7 microM, respectively.
The leaves of the Phoebe scortechinii (Gamb.) Kochummen Comb. Nov. (Lauraceae), afforded one new proaporphine-tryptamine dimer; (-)-phoebescortechiniine (1), along with two known ones; phoebegrandine A and phoebegrandine B. The proaporphine, tetrahydropronuciferine (2), was isolated for the first time as a natural product. The alkaloids were elucidated primarily by means of high field NMR and HRMS.
Phytochemical studies on the leaves and trunk bark of Garcinia cantleyana yielded five caged-xanthonoids including one tetra- and four tri-prenylated xanthones, cantleyanone A (1), 7-hydroxyforbesione (2) and cantleyanones B-D (4-6), as well as a simple xanthone, 4-(1,1-dimethylprop-2-enyl)-1,3,5,8-tetrahydroxyxanthone (3). Eight other known compounds, deoxygaudichaudione A, gaudichaudione H, friedelin, garbogiol, macranthol, glutin-5-en-3beta-ol, and a mixture of sitosterol and stigmasterol were also isolated. Their structures were elucidated by means of spectroscopic data and comparison of their NMR data with literature values. Significant cytotoxicity against MDA-MB-231, CaOV-3, MCF-7 and HeLa cancer cell-lines was demonstrated by cantleyanones B-D, 7-hydroxyforbesione, deoxygaudichaudione A and macranthol, with IC(50) values ranging from 0.22 to 17.17 microg/ml.
Two new xanthones, characterized as 4-(1,1-dimethylprop-2-enyl)-1,3,5,8-tetrahydroxyxanthone (1) and penangianaxanthone (2), with three known xanthones, cudratricusxanthone H (3), macluraxanthone C (4) and gerontoxanthone C (5), as well as friedelin and stigmasterol were isolated from the leaves of Garcinia penangiana. Their structures were elucidated by analysis of spectroscopic data and comparison of the NMR data with the literature ones. Significant cytotoxicity against DU-145, MCF-7 and NCI-H460 cancer cell lines was demonstrated by compounds 1-5, with IC50 values ranging from 3.5 to 72.8 microM.
A series of 46 curcumin related diarylpentanoid analogues were synthesized and evaluated for their anti-inflammatory, antioxidant and anti-tyrosinase activities. Among these compounds 2, 13 and 33 exhibited potent NO inhibitory effect on IFN-gamma/LPS-activated RAW 264.7 cells as compared to L-NAME and curcumin. However, these series of diarylpentanoid analogues were not significantly inhibiting NO scavenging, total radical scavenging and tyrosinase enzyme activities. The results revealed that the biological activity of these diarylpentanoid analogues is most likely due to their action mainly upon inflammatory mediator, inducible nitric oxide synthase (iNOS). The present results showed that compounds 2, 13 and 33 might serve as a useful starting point for the design of improved anti-inflammatory agents.
Phytochemical investigation on Globba pendula resulted in the isolation of a new naturally occurring 16-oxo-(8)17-12-labdadien-15,11-olide 1 and benzofuran-2-carboxaldehyde 2. Other known compounds including isoandrographolide, indirubin, vanillin, vanillic acid, 2(3H)-benzoxazolone, as well as beta-sitosteryl-beta-D-glucopyranoside, beta-sitosterol, and 7alpha-hydroxysitosterol were also isolated. The structures were established based on spectroscopic data and comparison with the literature. Furthermore, the compound isoandrographolide has demonstrated strong cytotoxic properties towards a panel of cancer cell lines (MCF-7, PC-3, and H-460) with the IC50 values of 7.9, 8.7, and 9.0 microM, respectively.
Detailed chemical studies on the roots of Piper sarmentosum and Piper nigrum have resulted in several alkaloids. The roots of P. sarmentosum gave a new aromatic compound, 1-nitrosoimino-2,4,5-trimethoxybenzene (1). Piper nigrum roots gave pellitorine (2), (E)-1-[3',4'-(methylenedioxy)cinnamoyl]piperidine (3), 2,4-tetradecadienoic acid isobutyl amide (4), piperine (5), sylvamide (6), cepharadione A (7), piperolactam D (8) and paprazine (9). Structural elucidation of these compounds was achieved through NMR and MS techniques. Cytotoxic activity screening of the plant extracts indicated some activity.
In a preliminary screen, Aaptos aaptos showed significant cytotoxic activity towards a panel of cell lines and was thus subjected to bioassay-guided isolation of the bioactive constituents. In addition to the known aaptamine, two new derivatives of the alkaloid were isolated from the bioactive chloroform fraction of the crude methanolic extract. Detailed analysis by NMR and mass spectroscopy enabled their identification to be 3-(phenethylamino)demethyl(oxy)aaptamine and 3-(isopentylamino)demethyl(oxy) aaptamine. The cytotoxic activities of the three alkaloids were further evaluated against CEM-SS cells.
Pellitorine (1), which was isolated from the roots of Piper nigrum, showed strong cytotoxic activities against HL60 and MCT-7 cell lines. Microbial transformation of piperine (2) gave a new compound 5-[3,4-(methylenedioxy)phenyl]-pent-2-ene piperidine (3). Two other alkaloids were also found from Piper nigrum. They are (E)-1-[3',4'-(methylenedioxy)cinnamoyl]piperidine (4) and 2,4-tetradecadienoic acid isobutyl amide (5). These compounds were isolated using chromatographic methods and their structures were elucidated using MS, IR and NMR techniques.
Phytochemical and cytotoxicity investigations on organic solvent extracts of the aerial parts of Tinospora crispa have led to the isolation of 15 cis-clerodane-type furanoditerpenoids. Of these, nine compounds (1-9) were found to be new. Spectroscopic assignments of a previously reported compound, borapetoside A (13), were revised on the basis of HMQC and HMBC correlations. No discernible activity was observed when compounds 10-13 were subjected to evaluation in cytotoxicity assays against human prostate cancer (PC-3) and the normal mouse fibroblast (3T3) cell lines.
Phylligenine, together with quebrachitol, stigmasterol and two aporphine alkaloids--oxoputerine and liriodenine--were isolated from the twigs of Mitrephora vulpina C.E.C. Fisch. They were evaluated for their ability to inhibit platelet activating factor (PAF) receptor binding to rabbit platelets using 3H-PAF as a ligand and their antiplatelet aggregation effect in human whole blood induced by arachidonic acid (AA), collagen and adenosine diphosphate (ADP). Of all the compounds tested, phylligenin and quebrachitol exhibited potent and concentration-dependent inhibitory effects on PAF receptor binding, with IC(50) values of 13.1 and 42.2 µM, respectively. The IC(50) value of phylligenin was comparable to that of cedrol (10.2 µM), a potent PAF antagonist. Phylligenin also showed strong dose-dependent inhibitory activity on platelet aggregation induced by AA and ADP.