Enhancing the water-solubility of curcuminoids-rich extract using a ternary inclusion complex system: Preparation, characterization, and anti-cancer activity.

Curcuminoids are known to exert diverse pharmacological effects and used in some pharmaceutical formulations. This study describes the preparation, characterization, and enhancement in the solubility and anticancer activity of a curcuminoids-rich extract (CRE) using a ternary inclusion complex system. CRE containing 88.9% w/w curcuminoids was prepared using a 'green' microwave extraction coupled with fractionation on a column of hydrophobic adsorbent resin. The ternary complex consisting of CRE, hydroxylpropyl-ß-cyclodextrin and polyvinylpyrrolidone K30 was prepared using the solvent evaporation method and thoroughly characterized using Fourier-transform infrared spectroscopy, powder X-ray diffractograms, differential scanning calorimetry and scanning electron microscopy. The ternary complex of CRE improved the water-solubility of curcuminoids (up to 70.3 µg/mL) as well as the dissolution rate when compared to those of CRE (0 µg/mL). In addition, the ternary complex exhibited significantly stronger anticancer activity against human lung adenocarcinoma (A-549), human cervical adenocarcinoma (HeLa) and human colon adenocarcinoma (HT-29) cell lines than CRE.

Non-competitive inhibition of acetylcholinesterase by bromotyrosine alkaloids.

Fifteen bromotyrosine-derived alkaloids were isolated from the sponge Pseudoceratina cf. purpurea. The acetylcholinesterase-inhibiting activity of all the isolated compounds were examined; to purealidin Q, isoanomoian A, aplyzanzine A, and aplysamine 2 were active with IC50 values of 1.2, 70, 104, and 1.3 µM, respectively. On the other hand, antiproliferative activity against MCF-7 cells of aerophobin 1 gave an IC50 value of 0.8 µM. The Michaelis-Menten plots of the active alkaloids indicated that all the four compounds inhibited acetylcholinesterase in a non-competitive manner. The structures of the active compounds suggested that the N,N-dimethylaminopropyloxydibromotyramine moiety may play an important role in the enzyme-inhibiting activity, presumably on the anionic and hydrophobic binding sites.

Three types of cytotoxic natural caged-scaffolds: pure enantiomers or partial racemates.

Two rare new natural products, the neocaged-xanthone pruniflorone T (1) and the rearranged caged-xanthone pruniflorone U (3), and the known caged-xanthone cochinchinone C (2) were isolated from the roots of Cratoxylum formosum ssp. pruniflorum. The unique structures of 1-3 were determined by analysis of NMR and X-ray diffraction data. The X-ray data of 1-3 revealed that they all exist with both enantiomers in their crystal packing. Separation of 1-3 by chiral HPLC led to the isolation of three pairs of enantiomers, (-)-1/(+)-1, (-)-2/(+)-2, and (-)-3/(+)-3, and their absolute configurations were determined by analysis of single-crystal X-ray diffraction and ECD spectroscopic data. A 1:1 mixture of 1 and 3 showed potent in vitro cytotoxicity against an MCF-7 human breast cancer cell line with an IC50 value of 0.11 µg/mL.

Carboxymethylcellulose-tetrahydrocurcumin conjugates for colon-specific delivery of a novel anti-cancer agent, 4-amino tetrahydrocurcumin.

Several curcumin derivatives are now becoming increasingly of interest because of their bioactive attributes, especially their action as antioxidants and anti-carcinogenic activities. Tetrahydrocurcumin (THC), an active metabolite of curcumin, was selected to be a proper starting material for the work presented here as it is stable in physiological pH and has the typical pharmacological properties of curcumin. We have now reported that novel synthesized water-soluble polymeric macromolecule prodrugs can specifically deliver the drug to the colon. To study the drug loading and drug release, THC was conjugated with a hydrophilic polymer, carboxymethylcellulose (CMC) with the degree of substitution (DS) values of 0.7 and 1.2. THC was also attached to two different spacers including p-aminobenzoic acid (PABA) and p-aminohippuric acid (PAH) via an azo bond that was cleaved by the azoreductase activities of colonic bacteria. The novel active molecule, 4-amino-THC, was readily released from the conjugates in the colon (>62% within 24h) with only very small amounts released in the upper GI tract (<12% over 12h). The polymer conjugates showed chemical stability at various pH values along the gastrointestinal tract and increased water solubility of up to 5mg/mL. 4-Amino-THC demonstrated cytotoxic ability against the human colon adenocarcinoma cell lines (HT-29) with an IC50 of 28.67 ± 1.01 µg/mL, and even greater selectivity (∼ 4 folds) to inhibit HT-29 cells than to normal human colon epithelial cell lines while curcumin was a non-selective agent against both cell lines. Our study has demonstrated that the use of THC-CMC conjugates may be a promising colon-specific drug delivery system with its sustained release in the colon to be an effective treatment for colonic cancer.

Antiproliferative effects of 12-oxoheteronemin vs heteronemin.

The antiproliferative activities of 12-oxoheteronemin and heteronemin were evaluated in six cancer cell lines and IC50 values ranging from 0.66 to 1.35 microM were obtained. In four of the cell lines, 12-oxoheteronemin and heteronemin were equipotent; however, in two estrogenic receptor-positive cell lines, heteronemin showed a stronger potency. Both compounds had no overt effects on cell cycle distribution in HeLa cells, but did rapidly initiate apoptosis as evidenced by increased sub-G1 populations of cells and caspase-dependent PARP cleavage.

3-oxoabolene and 1-oxocurcuphenol, aromatic bisabolanes from the sponge Myrmekioderma sp.

Two new aromatic bisabolane sesquiterpenes possessing an oxo functionality on the prenyl chain, (+)-3-oxoabolene (3) and (+)-l-oxocurcuphenol (4), along with two known sesquiterpenes, (+)-curcuphenol (1) and (+)-curcudiol (2), were isolated from the sponge Myrmekioderma sp. The antiproliferative activity of 2-4 was determined and showed an interesting selectivity; i.e., a good activity against HT-29 cells with IC50s in the microM range, but a weak and incalculable toxicity against Hela and normal fibroblast cells.

Bridged tricyclic sesquiterpenes from the tubercle nudibranch Phyllidia coelestis Bergh.

A new sesquiterpene, 1-formamido-10(1→2)-abeopupukeanane (1), was isolated from the tubercle nudibranch Phyllidia coelestis Bergh, along with 2-formamidopupukeanane (2), which is reported here as a natural product for the first time. A rearrangement pathway toward the unprecedented tricyclo[4.4.0.0(2,8)]decane skeleton is proposed. Both compounds showed antiproliferative activity when targeting HeLa, MCF-7, KB, and HT-29 cancer cell lines in the range 0.05-10 µM.

Anti-cancer activity of compounds from Bauhinia strychnifolia stem.

ETHNOPHARMACOLOGICAL RELEVANCE: The stem and root of Bauhinia strychnifolia Craib (Fabaceae family) have been traditionally used in Thailand to treat fever, alcoholic toxication, allergy and cancer. An EtOH extract of Bauhinia strychnifolia showed good inhibitory activity against several cancer cell lines including HT-29, HeLa, MCF-7 and KB. As there has been no previous reports on chemical constituents of Bauhinia strychnifolia, this study is aimed to isolate the pure compounds with anti-cancer activity. MATERIALS AND METHODS: Five pure compounds were isolated from EtOH extract of Bauhinia strychnifolia stem using silica gel, dianion HP-20 and sephadex LH-20 column chromatography and were tested for their cytotoxic effects against HT-29, HeLa, MCF-7 and KB cell lines using the Sulforhodamine B (SRB) assay. RESULTS: Among five compounds, 3,5,7,3',5'-pentahydroxyflavanonol-3-O-α-l-rhamnopyranoside (2) possessed very potent activity against KB (IC50=0.00054µg/mL), HT-29 (IC50=0.00217 µg/mL), MCF-7 (IC50=0.0585 µg/mL) and HeLa cells (IC50=0.0692 µg/mL). 3,5,7-Trihydroxychromone-3-O-α-l-rhamnopyranoside (3) also showed good activity against HT-29 (IC50=0.02366 µg/mL), KB (IC50=0.0412 µg/mL) and MCF-7 (IC50=0.297 µg/mL), respectively. The activity of 2 (IC50=0.00054 µg/mL) against KB cell was ten times higher than that of the positive control, Camptothecin (anti-cancer drug, IC50=0.0057 µg/mL). All compounds did not show any cytotoxicity with normal cells at the concentration of 1 µg/mL. CONCLUSION: This is the first report of compounds 2 and 3 on anti-cancer activity and based on the anti-cancer activity of extracts and pure compounds isolated from Bauhinia strychnifolia stem, it might be suggested that this plant could be useful for treatment of cancer.

Kabiramides J and K, trisoxazole macrolides from the sponge Pachastrissa nux.

Three trisoxazole macrolides possessing a 30-α,ß-enone moiety, including the known kabiramide G (1) and the new kabiramides J (2) and K (3), were isolated from the sponge Pachastrissa nux, along with the previously reported kabiramides B (4), C (5), and D (6). To date, the enone moiety has been found to associate solely with the trisoxazole macrolides from P. nux. All of the isolated macrolides showed moderate to strong antimalarial and cytotoxic activities, except for 1, which possessed only potent cytotoxicity.

Acetylcholinesterase-inhibiting activity of pyrrole derivatives from a novel marine gliding bacterium, Rapidithrix thailandica.

Acetylcholinesterase-inhibiting activity of marinoquinoline A (1), a new pyrroloquinoline from a novel species of a marine gliding bacterium Rapidithrix thailandica, was assessed (IC(50) 4.9 microM). Two related pyrrole derivatives, 3-(2'-aminophenyl)-pyrrole (3) and 2,2-dimethyl-pyrrolo-1,2-dihydroquinoline (4), were also isolated from two other strains of R. thailandica. The isolation of 3 from a natural source is reported here for the first time. Compound 4 was proposed to be an isolation artifact derived from 3. The two isolated compounds were virtually inactive in the acetylcholinesterase-inhibitory assay (enzyme inhibition < 30% at 0.1 g L(-1)).

Antitubercular sesterterpenes from the Thai sponge Brachiaster sp.

A new scalarane-type sesterterpene, 12-deacetoxyscalarin 19-acetate (2), and two naturally new derivatives of manoalide-type sesterterpenes, (E)- and (Z)-neomanoalide 24,25-diacetates (3 and 4), were isolated from the Thai sponge Brachiaster sp., along with five other known sesterterpenes: heteronemin (1), heteronemin acetate (5), 12-epi-19-deoxyscalarin (6), 12-deacetyl-12-epi-19-deoxyscalarin (7), and manoalide 25-acetate (8). The antitubercular and cytotoxic activities of all eight compounds were evaluated to reveal the potent activity of compounds 1, 2, 5, and 8. Among these, compound 2 showed an interesting bioactivity profile, in possessing potent antitubercular activity and being practically inactive in the cytotoxicity bioassay.

HIV-1 integrase inhibitory substances from Coleus parvifolius.

For the purpose of discovering anti-HIV-1 agents from natural sources, water and EtOH extracts of 50 Thai plants were screened for their inhibitory activity against HIV-1 integrase (IN), an enzyme essential for viral replication. Of these plants, an EtOH extract of Coleus parvifolius Benth. (aerial parts) showed potent activity against HIV-1 IN with an IC50 value of 9.2 microg/mL. From this extract, 11 compounds were isolated and identified as luteolin 5-O-beta-d-glucopyranoside (1), luteolin (2), luteolin 7-methyl ether (3), luteolin 5-O-beta-d-glucuronide (4), 5-O-beta-d-glucopyranosyl-luteolin 7-methyl ether (5), rosmarinic acid (6), rosmarinic acid methyl ester (7), daucosterol (8), a mixture of alpha- and beta-amyrin (9, 10) and phytol (11). Of these compounds, rosmarinic acid methyl ester (7), rosmarinic acid (6), luteolin (2) and luteolin 7-methyl ether (3) exhibited inhibitory activities against HIV-1 IN with IC50 values of 3.1, 5.0, 11.0 and 11.0 microM, respectively. Among rosmarinic acid derivatives, the HIV-1 IN inhibitory activity increased in turn for a dimer (IC50 = 5.0 microM), a trimer (IC50 = 1.4 microM), and a tetramer (IC50 = 1.0 microM).