Chemical constituents from the branches and leaves of Alchornea annamica.

Phytochemical investigation of the branches and leaves of Alchornea annamica led to isolation of ten secondary metabolites, including two new megastigmane glucosides alnamicosides A (1) and B (2). The structure elucidation was confirmed by 1 D and 2 D NMR, ECD as well as HR-QTOF-MS experiments. The megastigmane derivatives 1 - 3 exhibited inhibitory effects on LPS-induced NO production in RAW264.7 cells with IC50 values of 78.72 ± 1.90, 77.40 ± 9.40 and 82.16 ± 4.56 µM, respectively. This is the first report on chemical constituents and biological activity of the plant A. annamica.

Polyacetylene and phenolic constituents from the roots of Codonopsis javanica.

Chemical investigation of the roots of Codonopsis javanica resulted in isolation of 12 compounds, including one new polyacetylene, codojavanyol (1), one new phenolic glycoside, codobenzyloside (7), and 10 known compounds, (2E,8E)-9-(tetrahydro-2H-pyran-2-yl)nona-2,8-diene-4,6-diyl-1-ol (2), lobetyol (3), lobetyolin (4), lobetyolinin (5), cordifolioidyne B (6), benzyl-α-L-arabinopyranosyl (1-6)-ß-D-glucopyranoside (8), (Z)-8-ß-D-glucopyranosyloxycinnamic acid (9), syringin (10), syringaresinol (11), and tryptophan (12). Their structures were elucidated by 1 D and 2 D NMR and MS spectroscopic analyses in comparison with the data reported in the literature. The stereochemistry of the C-2' position of 1 was identified based on time-dependent density functional theory (TDDFT) electronic circular dichroism (ECD) calculation. Among the isolates, compounds 3-5 were shown to have weak cytotoxicity toward three human carcinoma cell lines, including lung (A549), liver (HepG2), and breast (MCF7), with the induction of 41.4 to 55.6% cell death at the concentration of 100 µM.

Chemical Constituents from the Branches and Leaves of Alchornea trewioides.

Two new megastigmane glucosides namely trewiosides A (1) and B (2), along with 20α-hydroxypregn-4-en-3-one ß-D-glucopyranoside (3), sugeroside (4), and schizandriside (5) were isolated from the branches and leaves of Alchornea trewioides. The structure elucidation was confirmed by extensive analysis of the one and two dimensional (1 and 2D) NMR, electronic circular dichroism (ECD) as well as high resolution electrospray ionization quadrupole time-of-flight (HR-ESI-QTOF) mass spectra. Noteworthily, the isolation of compounds 1 and 2 represents the second finding of megastigmane derivatives with a methoxycarbonyl group at C-5 to date. In addition, compound 3 showed weak cytotoxicity against three human cancer cell lines as A549 (lung carcinoma), HepG2 (hepatocarcinoma), and MCF7 (breast carcinoma). Besides, compounds 2 and 3 exhibited moderate inhibitory effects on lipopolysaccharide (LPS)-induced nitric oxide (NO) production in RAW264.7 cells. Whereas, the remaining compounds 1, 4 and 5 showed weak inhibitory activity.

Design, Synthesis and Bioevaluation of Two Series of 3-[(1-Benzyl-1H-1,2,3-triazol-4-yl)methyl]quinazolin-4(3H)-ones and N-(1-Benzylpiperidin-4-yl)quinazolin-4-amines.

Two series of 3-[(1-benzyl-1H-1,2,3-triazol-4-yl)methyl]quinazolin-4(3H)-ones and N-(1-benzylpiperidin-4-yl)quinazolin-4-amines were designed initially as potential acetylcholine esterase inhibitors. Biological evaluation demonstrated that N-(1-benzylpiperidin-4-yl)quinazolin-4-amines significantly inhibited AChE activity. Especially, two compounds of them were found to be the most potent with relative AChE inhibition percentages of 87 % in comparison to donepezil. The docking studies with AChE showed similar interactions between donepezil and four derivatives. N-(1-Benzylpiperidin-4-yl)quinazolin-4-amines also exhibited significant DPPH scavenging effects. The two series of compound also exerted moderate to good cytotoxicity against three human cancer cell lines, including SW620 (human colon cancer), PC-3 (prostate cancer), and NCI-H23 (lung cancer), with 3-[(1-benzyl-1H-1,2,3-triazol-4-yl)methyl]quinazolin-4(3H)-one being the most cytotoxic agent. 3-[(1-Benzyl-1H-1,2,3-triazol-4-yl)methyl]quinazolin-4(3H)-one significantly induced early apoptosis and arrested the SW620 cells at G2/M phase. From this study, two compounds of N-(1-benzylpiperidin-4-yl)quinazolin-4-amines could serve as new leads for further design and AChE inhibitors, while 3-[(1-benzyl-1H-1,2,3-triazol-4-yl)methyl]quinazolin-4(3H)-one could serve as a new lead for the design and development of more potent anticancer agents.

Novel 3,4-dihydro-4-oxoquinazoline-based acetohydrazides: Design, synthesis and evaluation of antitumor cytotoxicity and caspase activation activity.

In search for novel small molecules with antitumor cytotoxicity via activating procaspase-3, we have designed and synthesized three series of novel (E)-N'-benzylidene-4-oxoquinazolin-3(4H)-yl)acetohydrazides (5a-j, 6a-h, and 7a-h). On the phenyl ring ò the benzylidene part, three different substituents, including 2-OH-4-OCH3, 4-OCH3, and 4-N(CH3)2, were introduced, respectively. Biological evaluation showed that the acetohydrazides in series 5a-j, in which the phenyl ring of the benzylidene part was substituted by 2-OH-4-OCH3 substituent, exhibited potent cytotoxicity against three human cancer cell lines (SW620, colon; PC-3, prostate; NCI-H23, lung). Most of the compounds, in this series, especially compounds 5c, 5b and 5h, also significantly activated caspase-3 activity. Among these, compound 5c displayed 1.61-fold more potent than PAC-1 as caspase-3 activator. Cell cycle analysis showed that compounds 5b, 5c, and 5h significantly arrested the cell cycle in G1 phase. Further apoptotic studies also demonstrated compounds 5b, 5c, and 5h as strong apoptotic cell death inducers. The docking simulation studies showed that these compounds could activate procaspase via chelating Zn2+ ion bound to the allosteric site of the zymogen.

(E)-N'-Arylidene-2-(4-oxoquinazolin-4(3H)-yl) acetohydrazides: Synthesis and evaluation of antitumor cytotoxicity and caspase activation activity.

In our search for novel small molecules activating procaspase-3, we have designed and synthesised a series of novel acetohydrazides incorporating quinazolin-4(3H)-ones (5, 6, 7). Biological evaluation revealed eight compounds with significant cytotoxicity against three human cancer cell lines (SW620, colon cancer; PC-3, prostate cancer; NCI-H23, lung cancer). The most potent compound 5t displayed cytotoxicity up to 5-fold more potent than 5-FU. Analysis of structure-activity relationships showed that the introduction of different substituents at C-6 position on the quinazolin-4(3H)-4-one moiety, such as 6-chloro or 6-methoxy potentially increased the cytotoxicity of the compounds. In term of caspase activation activity, several compounds were found to exhibit potent effects, (e.g. compounds 7 b, 5n, and 5l). Especially, compound 7 b activated caspases activity by almost 200% in comparison to that of PAC-1. Further docking simulation also revealed that this compound potentially is a potent allosteric inhibitor of procaspase-3.

Quinazolin-4(3H)-one-Based Hydroxamic Acids: Design, Synthesis and Evaluation of Histone Deacetylase Inhibitory Effects and Cytotoxicity.

The present article describes the synthesis and biological activity of various series of novel hydroxamic acids incorporating quinazolin-4(3H)-ones as novel small molecules targeting histone deacetylases. Biological evaluation showed that these hydroxamic acids were potently cytotoxic against three human cancer cell lines (SW620, colon; PC-3, prostate; NCI-H23, lung). Most compounds displayed superior cytotoxicity than SAHA (suberoylanilide hydroxamic acid, Vorinostat) in term of cytotoxicity. Especially, N-hydroxy-7-(7-methyl-4-oxoquinazolin-3(4H)-yl)heptanamide (5b) and N-hydroxy-7-(6-methyl-4-oxoquinazolin-3(4H)-yl)heptanamide (5c) (IC50 values, 0.10-0.16 µm) were found to be approximately 30-fold more cytotoxic than SAHA (IC50 values of 3.29-3.67 µm). N-Hydroxy-7-(4-oxoquinazolin-3(4H)-yl)heptanamide (5a; IC50 values of 0.21-0.38 µm) was approximately 10- to 15-fold more potent than SAHA in cytotoxicity assay. These compounds also showed comparable HDAC inhibition potency with IC50 values in sub-micromolar ranges. Molecular docking experiments indicated that most compounds, as represented by 5b and 5c, strictly bound to HDAC2 at the active binding site with binding affinities much higher than that of SAHA.

N'-[(E)-Arylidene]-2-(2,3-dihydro-3-oxo-4H-1,4-benzoxazin-4-yl)-acetohydrazides: Synthesis and Evaluation of Caspase Activation Activity and Cytotoxicity.

In our search for novel small cytotoxic molecules potentially activating procaspase-3, we have designed and synthesized a series of novel N'-[(E)-arylidene]-2-(2,3-dihydro-3-oxo-4H-1,4-benzoxazin-4-yl)acetohydrazides (5, 6). Biological evaluation revealed that seven compounds, including 5h, 5j, 5k, 5l, 5n, 6a, and 6b, exhibited moderate to strong cytotoxicity against three human cancer cell lines (SW620, colon cancer; PC-3, prostate cancer; NCI-H23, lung cancer). Among these compounds, two most cytotoxic compounds (5h and 5j) displayed from 3- up to 10-fold higher potency than PAC-1 and 5-FU in three cancer cell lines tested. Three compounds 5j, 5k, and 5n were also found to display better caspases activation activity in comparison to PAC-1. Especially, compound 5k activated the level of caspases activity by 200% higher than that of PAC-1. From this study, three compounds 5j, 5k, and 5n could be considered as potential leads for further design and development of caspase activators and anticancer agents.

Two new simple iridoids from the ant-plant Myrmecodia tuberosa and their antimicrobial effects.

Six iridoid derivatives (1-6), including two new compounds myrmecodoides A and B (1 and 2), were isolated from the ant-plant Myrmecodia tuberosa. Their structures were determined on the basis of spectroscopic data ((1)H and (13)C NMR, HSQC, HMBC, (1)H-(1)H COSY, NOESY and HR-ESI-MS) and by comparison with the literature values. Among isolates, 3 and 4 exhibit weak antibacterial effect against Staphylococcus aureus subsp. aureus with MIC value of 100.0 µg/mL.

Anti-inflammatory tirucallane saponins from Paramignya scandens.

Five new tirucallane saponins, paramignyosides A-E (1-5), were isolated from the water fraction of the Paramignya scandens stem and leaves. Their structures were elucidated on the basis of spectroscopic evidence including high-resolution electrospray ionization mass spectrometry (HR-ESI-MS) and one dimensional (1D)- and 2D-NMR. The effects of isolated compounds on pro-inflammatory cytokines were evaluated by measuring the production of interleukin (IL)-12 p40, IL-6, and tumor necrosis factor-α (TNF-α) in lipopolysaccharide (LPS)-stimulated bone marrow-derived dendritic cells (BMDCs). Paramignyoside C (3) exhibited selective and potent inhibitory effect (IC50=5.03±0.19 µM) on the production of IL-12 p40 comparable to that of the positive control, SB203580 (IC50=5.00±0.16 µM). Further studies are required to confirm efficacy in vivo and the mechanism of anti-inflammatory effects.

Choice of healthcare provider following reform in Vietnam.

BACKGROUND: In Vietnam, the health-sector reforms since 1989 have lead to a rapid increase in out-of-pocket expenses. This paper examines the choice of medical provider and household healthcare expenditure for different providers in a rural district of Vietnam following healthcare reform. METHODS: The study consisted of twelve monthly follow-up interviews of 621 randomly selected households. The households are part of the FilaBavi project sample - Health System Research Project. The heads of household were interviewed at monthly intervals from July 2001 to June 2002. RESULTS: The use of private health providers and self-treatment are quite common for both episodes (60% and 23% of all illness episodes) and expenditure (60% and 12.8% of healthcare expenditure) The poor tend to use self-treatment more frequently than wealthier members of the community (31% vs. 14.5% of illness episodes respectively). All patients in this study often use private services before public ones. The poor use less public care and less care at higher levels than the rich do (8% vs.13% of total illness episodes, which decomposes into 3% vs. 7% at district level, and 1% vs. 3% at the provincial or central level, respectively). The education of the patients significantly affects healthcare decisions. Those with higher education tend to choose healthcare providers rather than self-treatment. Women tend to use drugs or healthcare services more often than men do. Patients in two highest quintiles use health services more than in the lowest quintile. Moreover, seriously ill patients frequently use more drugs, healthcare services, public care than those with less severe illness. CONCLUSION: The results are useful for policy makers and healthcare professionals to (i) formulate healthcare policies-of foremost importance are methods used to reduce self-treatment and no treatment; (ii) the management of private practices and maintaining public healthcare providers at all levels, particularly at the basic levels (district, commune) where the poor more easily can access healthcare services, is also important, as is the management of private practices and (iii) provide a background for further studies on both short and long-term health service strategies.

Household out-of-pocket payments for illness: evidence from Vietnam.

BACKGROUND: In Vietnam, illnesses create high out-of-pocket health care expenditures for households. In this study, the burden of illness in the Bavi district, Vietnam is measured based upon individual household health expenditures for communicable and non-communicable illnesses. The focus of the paper is on the relative effect of different illnesses on the total economic burden of health care on households in general and on households that have catastrophic health care spending in particular. METHODS: The study was performed by twelve monthly follow-up interviews of 621 randomly selected households. The households are part of the FilaBavi project sample--Health System Research Project. The heads of household were interviewed at monthly intervals from July 2001 to June 2002. RESULTS: For the population in the Bavi district, communicable illnesses predominate among the episodes of illness and are the reason for most household health care expenditure. This is the case for almost all groups within the study and for the study population as a whole. However, communicable illnesses are more dominant in the poor population compared to the rich population, and are more dominant in households that have very large, or catastrophic, health care expenditure, compared to those without such expenditures. CONCLUSION: The main findings indicate that catastrophic health care spending for a household is not usually the result of one single disastrous event, but rather a series of events and is related more to "every-day illnesses" in a developing country context than to more spectacular events such as injuries or heart illnesses.