Search

The most prevalent lung cancer is non-small cell lung cancer (NSCLC). This lung cancer type often develops other organ-specific metastases that are critical burdens in the treatment process. Orchid species in the genus Vanda have shown their potential in folkloric medication of diverse diseases but not all its species have been investigated, and little is known about their anticancer activities against NSCLC. Here, we firstly profiled the specialized metabolites of Vandabensonii and examined their capability to inhibit growth and metastasis of NSCLC using NCI-H460 cells as a study model. Four phytochemicals, including phloretic acid methyl ester (1), cymbinodin-A (2), ephemeranthoquinone B (3), and protocatechuic acid (4), were isolated from the whole plant methanolic extract of V. bensonii. The most distinguished cytotoxic effect on NCI-H460 cells was observed in the treatments with crude methanolic extract and compound 2 with the half maximal inhibitory concentrations of 40.39 μg mL−1 and 50.82 μM, respectively. At non-cytotoxic doses (10 μg mL−1 or 10 μM), only compound 1 could significantly limit NCI-H460 cell proliferation when treated for 48 h, while others excluding compound 4 showed significant reduction in cell proliferation after treating for 72 h. Compound 1 also significantly decreased the migration rate of NCI-H460 cells examined through a wound-healing assay. Additionally, the crude extract and compound 1 strongly affected survival and growth of NCI-H460 cells under anchorage-independent conditions. Our findings proved that natural products from V. bensonii could be promising candidates for the future pharmacotherapy of NSCLC.

From the whole plant of Dendrobium senile, a new phenanthrene namely 2,5,7-trihydroxy-4-methoxyphenanthrene (1) was isolated, together with seven known compounds including moscatin (2), 2,5-dihydroxy-4,9-dimethoxyphenanthrene (3), moscatilin (4), aloifol I (5), 4,4',8,8'-tetramethoxy[1,1'-biphenanthrene]-2,2',7,7'-tetrol (6), 2,2',7,7'-tetrahydroxy-4,4'-dimethoxy-1,1'-biphenanthrene (7) and bleformin G (8). The structure of the new compound was elucidated by analysis of its spectroscopic data. Moscatin (2) and 2,5-dihydroxy-4,9-dimethoxyphenanthrene (3) showed appreciable pancreatic lipase inhibitory effects when compared with the positive control orlistat.

Purpose: To examine the glucose uptake stimulatory activity of the root extract of Cissus javana DC. (Vitaceae) in Lδ myotubes of rat, and also to identify the extract’s active principles.Methods: The methanol extract was prepared from Cissus javana tuberous roots and evaluated for glucose uptake stimulatory effects on Lδ rat muscle cells and inhibitory activity against α-glucosidase. The chemical components were isolated using several chromatographic techniques, and their structures characterized by spectroscopic methods. Each isolate was then assayed for glucose uptake stimulatory and α-glucosidase inhibitory activities.Results: The extract (100 μg/ml) exhibited glucose uptake stimulatory effect (70.9 % enhancement) and α-glucosidase enzyme inhibitory activity (100 % inhibition). Through chromatographic separation, bergenin, stigmast-4-en-3-one and β-sitosterol were isolated and identified. Bergenin, at 100 μg/ml (0.3046 mM), increased glucose uptake by Lδ myotubes by 50.5 % without toxicity. At the same concentration, bergenin showed no inhibition on α-glucosidase enzyme, while stigmast-4-en-3-one and β-sitosterol exhibited 98.6 and 40.6 %, inhibition, respectively.Conclusion: This study is the first report on the chemical constituents, and the glucose uptake stimulatory and α-glucosidase inhibitory activities of Cissus javana DC. roots. The findings reveal the antidiabetic potential of the plant and the glucose-uptake enhancing activity of bergenin. Keywords: Cissus javana, α-Glucosidase, Antidiabetes, Rat skeletal muscle cells, Bergenin

Chemical investigation of Dendrobium delacourii revealed 11 phenolic compounds, and the structures of these compounds were determined by analysis of their NMR and HR-ESI-MS data. All compounds were investigated for their α-glucosidase inhibitory activity and anti-adipogenic properties. Phoyunnanin E (10) and phoyunnanin C (11) showed the most potent α-glucosidase inhibition by comparing with acarbose, which was used as a positive control. Kinetic study revealed the non-competitive inhibitors against the enzyme. For anti-adipogenic activity, densifloral B (3) showed the strongest inhibition when compared with oxyresveratrol (positive control). In addition, densifloral B might be responsible for the inhibition of adipocyte differentiation via downregulating the expression of peroxisome proliferator-activated receptor gamma (PPARγ) and CCAAT enhancer-binding protein alpha (C/EBPα), which are major transcription factors in adipogenesis.

Oxyresveratrol has recently attracted much research attention due to its simple chemical structure and diverse therapeutic potentials. Previous reviews describe the chemistry and biological activities of this phytoalexin, but additional coverage and greater accessibility are still needed. The current review provides a more comprehensive summary, covering research from 1955 to the present year. Oxyresveratrol occurs in both gymnosperms and angiosperms. However, it has never been reported in plants in the subclass Sympetalae, and this point might be of both chemotaxonomic and biosynthetic importance. Oxyresveratrol can be easily obtained from plant materials by conventional methods, and several systems for both qualitative and quantitative analysis of oxyresveratrol contents in plant materials and plant products are available. Oxyresveratrol possesses diverse biological and pharmacological activities such as the inhibition of tyrosinase and melanogenesis, antioxidant and anti-inflammatory activities, and protective effects against neurological disorders and digestive ailments. However, the unfavorable pharmacokinetic properties of oxyresveratrol, including low water solubility and poor oral availability and stability, have posed challenges to its development as a useful therapeutic agent. Recently, several delivery systems have emerged, with promising outcomes that may improve chances for the clinical study of oxyresveratrol.

Four new phenanthrene derivatives, gastrobellinols A-D (1&ndash, 4), were isolated from the methanolic extract of Gastrochilus bellinus (Rchb.f.) Kuntze, along with eleven known phenolic compounds including agrostophyllin (5), agrostophyllidin (6), coniferyl aldehyde (7), 4-hydroxybenzaldehyde (8), agrostophyllone (9), gigantol (10), 4-(methoxylmethyl)phenol (11), syringaldehyde (12), 1-(4&prime, hydroxybenzyl)-imbricartin (13), 6-methoxycoelonin (14), and imbricatin (15). Their structures were determined by spectroscopic methods. Each isolate was evaluated for &alpha, glucosidase inhibitory activity. Compounds 1, 2, 3, 7, 9, 13, and 15 showed higher activity than the drug acarbose. Gastrobellinol C (3) exhibited the strongest &alpha, glucosidase inhibition with an IC50 value of 45.92 &mu, M. A kinetic study of 3 showed competitive inhibition on the &alpha, glucosidase enzyme. This is the first report on the phytochemical constituents and &alpha, glucosidase inhibitory activity of G. bellinus.

Two new compounds, dihydrodengibsinin (1) and dendrogibsol (2), were isolated from the whole plant of Dendrobium gibsonii, together with seven known compounds (3&ndash, 9). The structures of the new compounds were elucidated by their spectroscopic data. All these isolates were evaluated for their &alpha, glucosidase inhibitory activities. Dendrogibsol (2) and lusianthridin (7) showed strong &alpha, glucosidase inhibitory activity when compared with acarbose. An enzyme kinetic study revealed that dendrogibsol (2) is a noncompetitive inhibitor of &alpha, glucosidase.

The phytochemical investigation of Huberantha jenkinsii resulted in the isolation of two new and five known compounds. The new compounds were characterized as undescribed 8-oxoprotoberberine alkaloids and named huberanthines A and B, whereas the known compounds were identified as allantoin, oxylopinine, N-trans-feruloyl tyramine, N-trans-p-coumaroyl tyramine, and mangiferin. The structure determination was accomplished by spectroscopic methods. To evaluate therapeutic potential in diabetes and Parkinson&rsquo, s disease, the isolates were subjected to assays for their &alpha, glucosidase inhibitory activity, cellular glucose uptake stimulatory activity, and protective activity against neurotoxicity induced by 6-hydroxydopamine (6-OHDA). The results suggested that mangiferin was the most promising lead compound, demonstrating significant activity in all the test systems.

From the aerial parts of Cymbidium ensifolium, three new dihydrophenanthrene derivatives, namely, cymensifins A, B, and C (1–3) were isolated, together with two known compounds, cypripedin (4) and gigantol (5). Their structures were elucidated by analysis of their spectroscopic data. The anticancer potential against various types of human cancer cells, including lung, breast, and colon cancers as well as toxicity to normal dermal papilla cells were assessed via cell viability and nuclear staining assays. Despite lower cytotoxicity in lung cancer H460 cells, the higher % apoptosis and lower % cell viability were presented in breast cancer MCF7 and colon cancer CaCo2 cells treated with 50 µM cymensifin A (1) for 24 h compared with the treatment of 50 µM cisplatin, an available chemotherapeutic drug. Intriguingly, the half-maximum inhibitory concentration (IC50) of cymensifin A in dermal papilla cells at >200 µM suggested its selective anticancer activity. The obtained information supports the further development of a dihydrophenanthrene derivative from C. ensifolium as an effective chemotherapy with a high safety profile for the treatment of various cancers.

The polyphenol compound, oxyresveratrol (OXY) possesses potent antioxidant and neuroprotective properties of potential utility in the treatment of Alzheimerʼs disease. However, the low oral bioavailability limits its neuroprotective effect and clinical application. The neuroprotective effect of orally administered OXY-loaded self-microemulsifying drug delivery system (OXY-SMEDDS) was compared with free OXY in vivo. Mice were orally administered either free OXY or OXY-SMEDDS once daily at a dose of 90, 180, or 360 mg/kg for 14 d. Mice received a single intracerebroventricular injection of the neurotoxic amyloid β (Aβ)25 – 35 peptide at day 8 during oral treatment. The OXY-SMEDDS formulation resulted in four-times reduction of the free OXY dose required for prevention of neurotoxicity effects due to Aβ 25 – 35 peptide as demonstrated by a significant decline in behavior impairments, lipid oxidation levels, and neuronal cell loss in all hippocampal subfields (p

Oxyresveratrol (ORV) is a naturally extracted compound with many pharmacological activities. However, information about the crystalline form is not known when considering the development of a form for oral dosage. Cocrystal engineering offers drug molecular understanding and drug solubility improvements. Thus, we attempted cocrystallization of ORV using 10 carboxylic acids as a coformer at a 1:1 M ratio. Each combination was processed with liquid-assisted grinding, solvent evaporation and a slurry method, then characterized by powder X-ray powder diffraction (PXRD), conventional and low-frequency Raman spectroscopy and thermal analysis. The solubility, dissolution and permeation studies across Caco-2 cell monolayers were conducted to evaluate the ORV samples. A screening study revealed that an ORV and citric acid (CTA) cocrystal formed by ethyl acetate-assisted grinding had characteristic PXRD peaks (14.0 and 16.5°) compared to those of ORV dihydrate used as a starting material. Low-frequency Raman measurements, with peaks at 100 cm-1, distinguished potential cocrystals among three processing methods while conventional Raman could not. An endothermic melt (142.2°C) confirmed the formation of the novel crystalline complex. The solubility of the cocrystal in the dissolution media of pH 1.2 and 6.8 was approximately 1000 µg/mL, a 1.3-fold increase compared to ORV alone. In vitro cytotoxicity studies showed that the cocrystal and physical blend were not toxic at concentrations of 25 and 12.5 µM ORV, respectively. The ORV-CTA cocrystal enhanced the cellular transport of ORV across Caco-2 monolayers. Therefore, cocrystallization could be used to improve aqueous solubility and permeability, leading to better oral bioavailability of ORV.

Phytochemical investigations of the leaves and stems of Pseuduvaria fragrans led to the isolation of a new benzophenone C-glucoside named pseuduvarioside (1), together with six known compounds including (&minus, )-guaiol (2), (+)-isocorydine (3), cyathocaline (4), isoursoline (5), N-trans-coumaroyltyramine (6), and N-trans-feruloyltyramine (7). Their structures were characterized by NMR spectroscopy and mass spectrometry. All of the isolates were evaluated for inhibitory activity against the enzyme &alpha, glucosidase. N-trans-coumaroyltyramine and N-trans-feruloyltyramine showed higher activity than the drug acarbose. Kinetic studies revealed that both tyramine-derived amides were uncompetitive inhibitors of the enzyme.

Roots of Boesenbergia rotunda (L.) Mansf. are prominent ingredients in the cuisine of several Asian countries, including Thailand, Malaysia, Indonesia, India, and China. An extract prepared from the roots of this plant showed strong inhibitory activity against enzymes α-glucosidase and pancreatic lipase and was subjected to chromatographic separation to identify the active components. Three new biflavonoids of the flavanone-chalcone type (9, 12, and 13) were isolated, along with 12 known compounds. Among the 15 isolates, the three new compounds showed stronger inhibitory activity against α-glucosidase than the drug acarbose but displayed lower pancreatic lipase inhibitory effect than the drug orlistat. The results indicated the potential of B. rotunda roots as a functional food for controlling after-meal blood glucose levels.

Oxyresveratrol (2,4,3′,5′-tetrahydroxystilbene, 1), a phytoalexin present in large amounts in the heartwood of Artocarpus lacucha Buch.-Ham., has been reported to possess a wide variety of biological activities. As part of our continuing studies on the structural modification of oxyresveratrol, a library of twenty-six compounds was prepared via O-alkylation, aromatic halogenation, and electrophilic aromatic substitution. The two aromatic rings of the stilbene system of 1 can be chemically modulated by exploiting different protecting groups. Such a strategy allows for selective and exclusive modifications on either ring A or ring B. All compounds were evaluated in vitro for a panel of biological activities, including free radical scavenging activity, DNA protective properties, antiherpetic activity, inhibition of α-glucosidase and neuraminidase, and cytotoxicity against some cancer cell lines. Several derivatives were comparably active or even more potent than the parent oxyresveratrol and/or the appropriate positive controls. The partially etherified analogs 5′-hydroxy-2,3′,4-trimethoxystilbene and 3′,5′-dihydroxy-2,4-dimethoxystilbene demonstrated promising anti-herpetic and DNA protective activities, offering new leads for neuropreventive agent research, whereas 5′-hydroxy-2,3′,4,-triisopropoxystilbene displayed anti-α-glucosidase effects, providing a new lead molecule for anti-diabetic drug development. 3′,5′-Diacetoxy-2,4-diisopropoxystilbene showed potent and selective cytotoxicity against HeLa cancer cells, but the compound still needs further in vivo investigation to verify its anticancer potential.

The physicochemical properties of the optimized microemulsion and the permeating ability of oxyresveratrol in microemulsion were evaluated, and the efficacy of oxyresveratrol microemulsion in cutaneous herpes simplex virus type 1 (HSV-1) infection in mice was examined. The optimized microemulsion was composed of 10% w/w of isopropyl myristate, 35% w/w of Tween 80, 35% w/w of isopropyl alcohol, and 20% w/w of water. The mean particle diameter was 9.67 ± 0.58 nm, and the solubility of oxyresveratrol in the microemulsion was 196.34 ± 0.80 mg/ml. After accelerated and long-term stability testing, the microemulsion base and oxyresveratrol-loaded microemulsion were stable. The cumulative amount of oxyresveratrol permeating through shed snake skin from microemulsion at 6 h was 93.04 times compared to that of oxyresveratrol from Vaseline, determined at 20% w/w concentration. In cutaneous HSV-1 infection in mice, oxyresveratrol microemulsion at 20%, 25%, and 30% w/w, topically applied five times daily for 7 days after infection, was significantly effective in delaying the development of skin lesions and protecting from death (p 0.05). These results demonstrated that topical oxyresveratrol microemulsion at 20–30% w/w was suitable for cutaneous HSV-1 mouse infection.

Three new prenylated 2-arylbenzofurans - artolakoochol, 4-hydroxy-artolakoochol and cycloartolakoochol - have been isolated from the root bark of Artocarpus lakoocha Roxb., Their structures were elucidated through analysis of their spectroscopic data, and their antiherpetic potential was evaluated by the plaque reduction assay.

Self-microemulsifying drug delivery systems (SMEDDS) containing two types (Tween80 and Labrasol) and two levels (low; 5% and high; 15%) of co-surfactants were formulated to evaluate the impact of surfactant phase on physical properties and oral absorption of oxyresveratrol (OXY). All formulations showed a very rapid release in the simulated gastric fluid (SGF) pH 1.2. After dilution with different media, the microemulsion droplet sizes of the Tween80-based (∼26 to 36 nm) were smaller than that of the Labrasol-based systems (∼34 to 45 nm). Both systems with high levels of surfactant increased the Caco-2 cells permeability of OXY compared to those with low levels of surfactant (1.4-1.7 folds) and the unformulated OXY (1.9-2.0 folds). It was of interest, that there was a reduction (4.4-5.3 folds) in the efflux transport of OXY from both systems compared to the unformulated OXY. The results were in good agreement with the in vivo absorption studies of such OXY-formulations in rats. Significantly greater values of Cmax and AUC(0-10h) (p

A total of 25 phenolic compounds were studied for their inhibitory effects against herpes simplex virus (HSV)-1, HSV-2, and human immunodeficiency virus (HIV)-1. These include five flavonoids (1–5) and two dimeric stilbenes (6,7) from Artocarpus gomezianus. Wall. ex trec., five phloroglucinol derivatives (8–12) from Mallotus pallidus. (Airy Shaw) Airy Shaw, and 13 courmarins (13–25) from Triphasia trifolia. (Burm.f.) P. Wilson. The data obtained in this study suggest the bis-hydroxyphenyl structure as a potential target for anti-HSV and HIV drugs development.

Purpose: To modify the structure of oxyresveratrol and evaluate the obtained derivatives for effects on neuronal cells. Methods: Electron-withdrawing groups were selectively introduced to the aromatic ring of the core stilbene structure. Oxyresveratrol and derivatives were then evaluated for their ability to enhance the survival of P19 derived neuronal cells by XTT method, in comparison with the widely known antioxidants, Trolox and ascorbic acid. Phase-contrast microscopic images of the neurons under various conditions were also taken and analyzed. Results: Oxyresveratrol, at a very low concentration (1 ng/mL), enhanced the survival of neurons in both normal and serum-deprivation conditions. Higher activity was observed for the 5-formylated and t 5-carboxylated products. The potencies of these polyoxygenated stilbenes were far greater than those of Trolox and ascorbic acid. These observations were supported by results from the examination of the phase-contrast micrographs of the neuronal cells. Conclusion: Oxyresveratrol and some derivatives prepared in this study demonstrate significant cell protective activity and may be of therapeutic value, but further investigations in animals are required to verify their neuroprotective potentials. Keywords: Oxyresveratrol, Artocarpus lacucha , Artocarpus lakoocha , Polyoxygenated stilbenes, Cell protection, Neuron

Phytochemical investigation of the stem of Dendrobium capillipes resulted in the isolation of a new flavonol glycoside namely quercetin-3-O-α-l-rhamnopyranosyl-(1 → 2)-β-d-xylopyranoside, along with seven known phenolic compounds which included two flavonol glycosides and five bibenzyls. From the stem of Dendrobium secundum, a new compound named 5-hydroxy-3,4,3′,4′,5′-pentamethoxybibenzyl was characterized, together with two known bibenzyls and three glycosidic flavonoids. Some of the isolated bibenzyls showed cytotoxicity against KB, NCI-H187, and MCF-7 cancer cells, whereas all of the glycosidic flavonoids were devoid of activity.

A number of Dendrobium species (Orchidaceae) have been used as health foods. In Thailand, the tea prepared from the stems of Dendrobium draconis Rchb.f. (Orchidaceae) has been used as a blood tonic. Our phytochemical investigation of this plant led to the isolation of a new compound namely 5-methoxy-7-hydroxy-9,10-dihydro-1,4-phenanthrenequinone, along with four known stilbenoids including hircinol, gigantol, batatasin III, and 7-methoxy-9,10-dihydrophenanthrene-2,4,5-triol. The structures of these compounds were determined through extensive spectroscopic studies, including (1)H and (13)C NMR, DEPT, COSY, NOESY, HMQC, HMBC, ESI-MS, and HR-ESI-MS experiments. In the DPPH-free radical assay, these stilbene derivatives showed appreciable antioxidant activity.

Biological evaluation of extracts prepared from the tubers of Stephania pierrei revealed cytotoxic and antimalarial activity. During the course of separation, two new aporphine alkaloids, (-)-asimilobine-2-O-beta-D-glucoside [2] and (-)-nordicentrine [8], in addition to twenty-one known isoquinoline alkaloids, were isolated. Each isolate was assessed for cytotoxic and antimalarial activities. It was found that the cytotoxicity of S. pierrei was mainly due to the presence of the aporphine alkaloids containing the 1,2-methylenedioxy group 3-10, whereas the antimalarial activity was attributed to the nonquaternary aporphine alkaloids 1, 3-10 and the tetrahydroprotoberberines possessing a phenolic functionality, 13-15, 18. None of the isolates showed a degree of selectivity comparable to that of antimalarial drugs such as chloroquine, quinine, mefloquine, and artemisinin. Comparison of the alkaloid content of S. pierrei and Stephania erecta strongly suggested separate identities for the two plants.

Complete 1H-nmr data and unambiguous assignments of the 13C-nmr spectra of phyllanthin [1] and hypophyllanthin [2] were obtained through extensive nmr studies, including homonuclear COSY, homonuclear decoupling, APT, HETCOR, nOe difference, selective INEPT, and COLOC experiments. The absolute configuration of hypophyllanthin [2] was determined by cd. Neither of these lignans demonstrated significant cytotoxic activity when evaluated with a battery of cultured mammalian cells, but both were found to enhance the cytotoxic response mediated by vinblastine with multidrug-resistant KB cells. In addition, 1 was found to displace the binding of vinblastine with membrane vesicles derived from this cell line, suggesting an interaction with the P-glycoprotein.

From the twigs of Miliusa mollis Pierre, three new compounds including (2S,3S)-2,3-dihydro-2-(4-methoxyphenyl)-3-methyl-5-[1(E)-propenyl]benzofuran, (7S,8S)- threo-Delta8'-4-methoxyneolignan and tyrosol-1-O-beta-xylopyranosyl-(1-->6)-O-beta-gluco-pyranoside were isolated, along with seven known compounds. Their structures were elucidated through analysis of their spectroscopic data.

Fourteen compounds isolated from Stephania venosa, Prismatomeris sessiliflora, Diospyros montana and Murraya siamensis were tested for their antimalarial potential. The 6a,7-dehydroaporphine alkaloids dehydrostephanine and dehydrocrebanine showed potent activity with IC50 values of 40 and 70 ng/ml, respectively. The 13C-NMR data of rubiadin, rubiadin-1-methyl ether, diospyrin and 5-hydroxy-4-methoxy-2-naphthal-dehyde were extensively studied.

The heartwood extract of Artocarpus lakoocha Roxb. was evaluated for the in vitro tyrosinase inhibitory activity and the in vivo melanin-reducing efficacy in human volunteers. The IC(50) of the extract and oxyresveratrol, its major active ingredient, against mushroom tyrosinase was determined to be 0.76 and 0.83 mug mL(-1), respectively. The extract dissolved in propylene glycol was subsequently tested in female volunteers using a parallel clinical trial with self-control (n = 20 per group). The first group received the 0.25% w/v A. lakoocha solution as the test solution, whereas the second and the third group, respectively, received 0.25% licorice extract and 3% kojic acid as the reference solutions in the same solvent. The subjects in each group twice daily applied the test (or reference) solution in one of her upper arm, whereas the remaining arm was treated with only propylene glycol (self-control) for 12 weeks. The melanin content of each application site was measured using Mexameter every week and calculated as % reduction in melanin content relative to the initial melanin value (% whitening). The value of % whitening was then compared between the product-treated and the propylene glycol-treated arms within the same subject using paired t-test (alpha = 0.05). The A. lakoocha extract was the most effective agent, giving the shortest onset of significant whitening effect after only 4 weeks of application (P < 0.05), followed by 3% kojic acid (6 weeks) and 0.25% licorice extract (10 weeks). The effect also increased with time with maximum whitening observed at week 12 for A. lakoocha extract. When the extract was formulated as an oil-in-water emulsion, its whitening efficacy was further enhanced. Daily application of 0.1% w/w A. lakoocha lotion to the upper arms (n = 25) and cheeks (n = 15) of volunteers produced significant whitening over the lotion base after 2 and 3 weeks, respectively (P < 0.05). Thus, the preliminary study suggested that the heartwood extract of A. lakoocha may have a promising potential for use as an effective and economical skin-whitening agent.

Five xanthones from the bark of Garcinia cowa, namely 7-O-methylgarcinone E (1), cowanin (2), cowanol (3), cowaxanthone (4), and beta-mangostin (5), were found to possess in vitro antimalarial activity against Plasmodium falciparum with IC50 values ranging from 1.50 to 3.00 micrograms/ml. Complete 1H- and 13C-NMR assignments of these compounds are also reported.

From oxyresveratrol (trans-2,4,3',5'-tetrahydroxystilbene 1), seven derivatives were prepared, including trans-2-methoxy-4,3',5'-trihydroxystilbene (2), trans-2,3'-dimethoxy-4,5'-dihydroxystilbene (3), trans-4,3'-dimethoxy-2,5'-dihydroxystilbene (4), trans-2,4,3',5'-tetramethoxystilbene (5) and cis-2,4,3',5'-tetramethoxystilbene (6), 2,4,3',5'-tetrahydroxybibenzyl (7), and 2,4,3',5'-tetramethoxybibenzyl (8). The tetrahydroxybibenzyl 7, a hydrogenation product of 1, exhibited more potent tyrosinase inhibitory activity than the parent compound, without cytotoxicity. A kinetic study revealed that 7 was a reversible and non-competitive inhibitor of mushroom tyrosinase with l-dopa as the substrate. Analysis of the K(i) values indicated that 7 has a slightly higher affinity to the enzyme than 1. Compound 6, a tetra-O-methylated analogue of 1 with cis-configuration, was deprived of inhibitory effect on the enzyme tyrosinase, but showed very strong cytotoxicity against the human cancer cells KB, BC, and NCI-H187, with potency comparable to those of the anticancer agents ellipticine and doxorubicin. Data on the tyrosinase inhibitory activity and cytotoxicity of 1-8 indicated that O methylation on stilbene 1 destroyed anti-tyrosinase activity but generated cytotoxicity. Thus, facile preparations of a potent tyrosinase inhibitor (7) and a strong cytotoxic agent (6) from the natural product 1 were achieved through simple chemical reactions.

Fom the stem wood of Dracaena loureiri, a new homoisoflavanone named loureiriol (1) and eight known flavonoid and stilbenoid derivatives, including 5,7-dihydroxy-3-(4-hydroxybenzyl)-4-chromanone (2), 4,4'-dihydroxy-2,6-dimethoxydihydrochalcone (3), 2,4'-dihydroxy-4,6-dimethoxydihydrochalcone (4), 4'-hydroxy-2,4,6-trimethoxydihydrochalcone (5), 4,6,4'-trihydroxy-2-methoxydihydrochalcone (6), 4,3',5'-trihydroxystilbene (7), 4,3'-dihydroxy-5'-methoxystilbene (8) and 4-hydroxy-3',5'-dimethoxystilbene (9) were isolated. These compounds were evaluated for their inhibitory activity against the enzymes cyclooxygenase-1 and cyclooxygenase-2. Potent but non-selective activity was found for the stilbenoids 7-9 (IC(50) 1.29 - 4.92 microM) whereas weak or no activity was observed for the flavonoids 1-6.

Two new biflavonoids, namely, 6'"-hydroxylophirone B (1) and 6'"-hydroxylophirone B 4"'-O-beta-glucoside (2), were isolated from the stem bark of Ochna integerrima, together with five known compounds. The structures of 1 and 2 were determined by spectral data interpretation.

From the stem bark of Millettia erythrocalyx, three new compounds, namely, millettocalyxins A-C (1-3), and the new natural product pongol methyl ether (4) were isolated, along with 10 other known compounds. The structures of the new isolates were elucidated on the basis of spectroscopic data interpretation.

A new dimeric stilbene, namely, artogomezianol (1), and the known compound andalasin A (2) were isolated from the roots of Artocarpus gomezianus. Both 1 and 2 showed moderate tyrosinase inhibitory activity with IC(50) values of 68 and 39 microM, respectively.

Eight compounds including, phenyl-beta-naphthylamine (1), isocyclomorusin (2), cycloartocarpin (3), artocarpin (4), norartocarpetin (5), cudraflavone C (6), albanin A (7), and resveratrol (8) were isolated from the roots of Artocarpus gomezianus. Compounds 5 and 8 exhibited potent tyrosinase inhibitory activity. The 1H- and 13C-NMR properties of 1, 3 and 8 were extensively studied.

Roots of Nepenthes thorelii yielded plumbagin, 2-methylnaphthazarin, octadecyl caffeate, isoshinanolone, and droserone. In addition, seven derivatives were prepared from plumbagin. Each of these natural and semisynthetic compounds was evaluated for in vitro antimalarial potential.

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.

The structure of pyramidatine [1], a new bisamide alkaloid from leaves of Aglaia pyramidata, was determined through extensive nmr studies, including homonuclear COSY, NOESY, APT, HETCOR, and selective INEPT techniques. Revision of the 13C-nmr assignment of piriferine [2], an alkaloid previously isolated from A. pirifera, was achieved by examination of several 2D nmr spectra (homonuclear COSY, NOESY, and HETCOR) and confirmed by selective INEPT nmr experiments. Evaluation of the cytotoxic potential of the two alkaloids, along with two other bisamides from Aglaia odorata, odorine [3] and 5'-epi-odorine [4], was carried out in eleven human cancer cell lines. None of these bisamides showed significant cytotoxicity. Nevertheless, piriferine [2], odorine [3], and 5'-epi-odorine [4] were found to inhibit the growth of the vinblastine-resistant KB cells by enhancing the anticancer activity of vinblastine.

(+)-2-N-Methyltelobine [1], a new alkaloid, together with twelve known bisbenzylisoquinolines, was isolated from the tubers of Stephania erecta. The structure determination and the complete 1H- and unambiguous 13C-nmr assignments of 1 were obtained through extensive use of several 1D and 2D nmr techniques. All alkaloids inhibited the growth of cultured Plasmodium falciparum strains D-6 and W-2 and displayed nonselective cytotoxicity with a battery of cultured mammalian cells. These data were used for the calculation of selectivity indices. Relative to known antimalarial agents, these bisbenzylisoquinoline alkaloids do not appear to be promising clinical candidates at the present time.

Chromatographic separation of the EtOH extract of the bark of Garcinia dulcis (Guttiferae) furnished five xanthones, viz 1,7-dihydroxyxanthone (1), 12b-hydroxy-des-D-garcigerrin A (2), 1-O-methylsymphoxanthone (3), symphoxanthone (4), and garciniaxanthone (5). These xanthones 1-5 showed inhibitory effects on the growth of Plasmodium falciparum with IC50 values of 0.96-3.88 micrograms/ml. In addition, revised 13C-NMR assignments of 3 and complete 13C-NMR assignments of 4 were obtained through analysis of their COSY, NOESY, HMQC, and HMBC spectra.

Six components have been isolated from the bark of Michelia rajaniana, and their structures have been determined by spectroscopic analysis. Four of the components have been reported previously: The germacranolide (-)-parthenolide and the oxoaporphinoid alkaloid liriodenine have been observed as constituents of several species, and (-)-bisparthenolidine and (+)-paramicholide have been reported recently by us as constituents of Paramichelia baillonii. The two new components 3 and 4, which are novel derivatives of parthenolide and contain an unusual N-acetyl substituent at C-13, have been given the names (+)-N-acetylparthenolidine and (+)-N-acetyl-8 alpha-hydroxyparthenolidine, respectively. The crude CHCl3 extract of the bark of M. rajaniana exhibited strong cytotoxicity in the KB cell culture assay.