Copper-azide nanoparticle: a 'catalyst-cum-reagent' for the designing of 5-alkynyl 1,4-disubstituted triazoles.

A single pot, wet chemical route has been applied for the synthesis of polymer supported copper azide, CuN3, nanoparticles (CANP). The hybrid system was used as 'catalyst-cum-reagent' for the azide-alkyne cyclo-addition reaction to construct triazole molecules using substituted benzyl bromide and terminal alkyne. The electron donating group containing terminal alkyne produced 5-alkynyl 1,4-disubstituded triazole product whereas for alkyne molecule with terminal electron withdrawing group facilitate the formation of 1,4-disubstituted triazole molecule.

A bis-indole/carbazole based C5-curcuminoid fluorescent probe with large Stokes shift for selective detection of biothiols and application to live cell imaging.

A series of heterocyclic C5-curcuminoids (bis(arylmethylidene)acetones) (PJ1-PJ6) having a large Stokes shift (Δλ = 104-173 nm) have been synthesized for the selective detection of cysteine (Cys), homocysteine (Hcy) and glutathione (GSH) in living cells. The compounds were synthesized using a new methodology via deacetylation under microwave conditions. The photophysical properties of these compounds have been studied. Prominent colour changes from bright yellow to colourless in the presence of thiols were observed for PJ1. Live cell imaging has been employed with PJ1 for the utilization of the probe to detect homocysteine in A375 cells and apoptosis in AGS cells.

Carbon nitride supported copper nanoparticles: light-induced electronic effect of the support for triazole synthesis.

The composite framework of graphitic carbon nitride (gCN) supported copper nanoparticle can act as a high-performance photoreactor for the synthesis of 1,2,3-triazole derivatives under light irradiation in the absence of alkaline condition. The photoactivity of gCN originates from an electron transition from the valence band to the conduction band, in the presence of photon energy, and the hot electron acts as a scavenger of the terminal proton of the alkyne molecule to facilitate the formation of copper acetanilide complex. In this study, we have performed the experiment under a different photonic environment, including dark condition, and in the presence and absence of base. A comparative study was also executed using Cu-TiO2 system, as a reference material, in the support of our proposed mechanism. The recycling performance and the photocorrosion effect of the catalyst have also been reported in this study.

Light effect on Click reaction: Role of photonic quantum dot catalyst.

Due to the light excitation, the valence band electron of the copper (I) sulfide quantum dot transfer to the conduction band and act as a scavenger of the terminal proton of the alkyne in the presence of organic azide with the formation of 1,4-disubstituted 1,2,3-triazoles, where the copper(I) species of Cu2S act as a catalyst for the reaction. The above cycloaddition reaction between alkyne and azide is commonly known as the Click reaction. In this study, experiments were carried out under the exposure of ultra-violate and daylight and also dark environment. According to the original recommendation for the Click reaction, the role of the base was also considered for this experiment. We found that the effect of conduction band electron is more efficient than the recommended conventional base mediated reaction procedure.

One-step synthesis of isocoumarins and 3-benzylidenephthalides via ligandless Pd-catalyzed oxidative coupling of benzoic acids and vinylarenes.

A straightforward synthetic method for the preparation of isocoumarins and 3-benzylidenephthalides via C-H olefination and oxidative coupling of readily available benzoic acids and vinylarenes was developed. The directing effect of the substituents on the benzoic acid allows for the synthesis of both types of lactone in pure form.

Regulation of NF-κB activation through a novel PI-3K-independent and PKA/Akt-dependent pathway in human umbilical vein endothelial cells.

The transcription factor NF-κB regulates numerous inflammatory diseases, and proteins involved in the NF-κB-activating signaling pathway are important therapeutic targets. In human umbilical vein endothelial cells (HUVECs), TNF-α-induced IκBα degradation and p65/RelA phosphorylation regulate NF-κB activation. These are mediated by IKKs (IκB kinases) viz. IKKα, ß and γ which receive activating signals from upstream kinases such as Akt. Akt is known to be positively regulated by PI-3K (phosphoinositide-3-kinase) and differentially regulated via Protein kinase A (PKA) in various cell types. However, the involvement of PKA/Akt cross talk in regulating NF-κB in HUVECs has not been explored yet. Here, we examined the involvement of PKA/Akt cross-talk in HUVECs using a novel compound, 2-methyl-pyran-4-one-3-O-ß-D-2',3',4',6'-tetra-O-acetyl glucopyranoside (MPTAG). We observed that MPTAG does not directly inhibit IKK-ß but prevents TNF-α-induced activation of IKK-ß by blocking its association with Akt and thereby inhibits NF-κB activation. Interestingly, our results also revealed that inhibitory effect of MPTAG on Akt and NF-κB activation was unaffected by wortmannin, and was completely abolished by H-89 treatment in these cells. Thus, MPTAG-mediated inhibition of TNF-α-induced Akt activation was independent of PI-3K and dependent on PKA. Most importantly, MPTAG restores the otherwise repressed activity of PKA and inhibits the TNF-α-induced Akt phosphorylation at both Thr308 and Ser473 residues. Thus, we demonstrate for the first time the involvement of PKA/Akt cross talk in NF-κB activation in HUVECs. Also, MPTAG could be useful as a lead molecule for developing potent therapeutic molecules for diseases where NF-κB activation plays a key role.

Anti-leukemic activity of Wattakaka volubilis leaf extract against human myeloid leukemia cell lines.

ETHNOPHARMACOLOGICAL RELEVANCE: Wattakaka volubilis has been traditionally used in Ayurvedic medicine in India for treatment of several ailments such as bronchial asthma, inflammations, tumors, piles, leucoderma, application to boils, rat bite etc. AIM OF THE STUDY: The present study was designed to investigate anti-leukemic activity of the crude aqueous methanolic extract and to identify active compounds from the leaves of Wattakaka volubilis. MATERIALS AND METHODS: The leaves of Wattakaka volubilis were extracted with aqueous methanol. Liquid-liquid fractionation of the crude methanolic extract with different organic solvents was done and the fractions were screened for in vitro anti-leukemic activity using different leukemic cell lines. The active fractions were then subjected to chromatographic separation for isolation of bioactive compounds. Structure of isolated compound was elucidated by spectroscopic methods. The in vitro anti-leukemic activities of different extracts of the leaves and isolated compound WVP were studied in U-937, HL-60 and K-562 cell-lines by using cell count, MTT [(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide] and DNA laddering assays, flow-cytometric and confocal microscopic techniques. RESULTS: Kaempferol-3-O-[α-l-rhamnopyranosyl-(1→4)-O-α-l-rhamnopyranosyl-(1→6)-O]-ß-d-glucopyranoside (WVP) was isolated from crude leaves extract of Wattakaka volubilis. Both the n-butanolic extract (WVB) of Wattakaka volubilis and its isolate WVP were found to be responsible for in vitro anti-leukemic activity. The IC(50) values of WVB were found be 120, 100 and 50(µg/ml) in U937, K562, and HL-60 cell lines, respectively. Whereas, the pure isolate WVP exhibited anti-leukemic activity with IC(50) values of 13.5, 10.8, and 13.2(µg/ml) in U937, K562, and HL-60 cell lines, respectively. The flow-cytometric analysis confirms that the cell cycle arrest occurs at G1 phase in case of U937 and K562 cell lines and G2/M phase in case of HL60 cell lines. Similarly both confocal microsocopic analysis and DNA laddering assay confirm the apoptosis and cell cycle arrests of leukemic cells. CONCLUSION: The overall results provide evidence for the ethnopharmacological relevance for use of the plant Wattakaka volubilis in developing novel agents for the treatment of leukemia.

Pd(0)-catalyzed decarboxylative coupling and tandem C-H arylation/decarboxylation for the synthesis of heteroaromatic biaryls.

An effective Pd(0) carbene complex was successfully employed in the decarboxylative coupling of the heteroaromatic carboxylic acids (imidazo[1,2-a]pyridine and isoxazole) with aryl halides. For carboxyindoles, either decarboxylative coupling or tandem C-H arylation and decarboxylation occurred, leading to the formation of C2-monoarylated indoles.

Ethyl gallate isolated from Pistacia integerrima Linn. inhibits cell adhesion molecules by blocking AP-1 transcription factor.

ETHNOPHARMACOLOGICAL RELEVANCE: Galls from Pistacia integerrima Linn. (kakadshringhi) have been used as therapeutic agent for various inflammatory diseases in Indian system of traditional medicine. However, the active constituents underlying the medicinal properties of the Pistacia integerrima Linn. have not been thoroughly investigated yet. AIM OF THE STUDY: Deregulated expression of cell adhesion molecules (CAMs) on vascular endothelium aggravates the inflammatory condition in various chronic diseases. In this work, we aimed to identify the active constituent from leaf gall of Pistacia integerrima Linn. using CAMs expression assay in activity guided purification, followed by determining the molecular mechanism of action. MATERIAL AND METHODS: Cell based ELISA for LPS induced CAMs expression in human vein endothelial cells (HUVECs) was used for the activity guided isolation form Pistacia galls followed by structural determination of active constituent using IR, MS and NMR spectroscopy. Mechanism of action of the active constituent was investigated by western blot, RT-PCR and EMSA experiments. RESULTS: In our study, ethyl gallate (EG) was identified as the active constituent of Pistacia integerrima Linn. for mediating its anti-inflammatory activity. It significantly attenuated LPS induced ICAM-1 and VCAM-1 at the protein and mRNA levels. At a functional level, it inhibited the adhesion of neutrophils to LPS activated endothelium. To identify its mechanism of action, we demonstrated that EG inhibited LPS induced cell adhesion molecules expression by blocking AP-1 transcription factor without affecting nuclear transcription factor-κB (NF-κB). CONCLUSION: Our results suggest that EG could be useful as a lead molecule for developing therapeutic agent for various inflammatory diseases.

Antioxidant and antibacterial activities of bark extracts from Commiphora berryi and Commiphora caudata.

This study investigates the in vitro antioxidant and antimicrobial activities of eight extracts obtained from the dried barks of Commiphora berryi and Commiphora caudata (Burseraceae). The radical scavenging activity was assessed by 1,1-diphenyl-2-picryl hydrazyl (DPPH) and nitric oxide assays. The methanolic extracts of C. berryi and C. caudata showed significant DPPH radical scavenging activity, with IC50 values of 26.92 and 21.16 µg mL⁻¹, respectively, and low radical scavenging activity against the nitric oxide assay. The antimicrobial activity of the plants was tested against the Gram-positive and Gram-negative bacteria. The ethyl acetate, chloroform and petroleum ether extracts of C. berryi showed good antibacterial activity against Pseudomonas aeruginosa, with a minimum inhibitory concentration (MIC) of 0.26 mg mL⁻¹, whereas the ethyl acetate and methanol extracts of C. caudata showed moderate antimicrobial activity with an MIC of more than 2.0 mg mL⁻¹ against P. aeruginosa compared to the petroleum ether and chloroform extracts, which showed an MIC of 1.1 mg mL⁻¹. The methanolic extracts of C. berryi and C. caudata also showed moderate cytotoxic activity against a human mammary carcinoma cell line (MCF-7), with values IC50 of 82.6 and 88.4 µg mL⁻¹, respectively.

2-Methyl-pyran-4-one-3-O-ß-D-glucopyranoside isolated from leaves of Punica granatum inhibits the TNFα-induced cell adhesion molecules expression by blocking nuclear transcription factor-κB (NF-κB).

Here, we report bioactivity-guided isolation, purification and characterization of a novel compound, 2-methyl-pyran-4-one-3-O-ß-d-glucopyranoside (MPG) from the leaves of Punica granatum. The structure of MPG was established on the basis of its detailed spectral analyses. We demonstrated that MPG not only inhibited the expression of cell adhesion molecules but also significantly blocked its functional consequence, that is, the adhesion of neutrophils on human endothelial cells monolayer. To elucidate the molecular mechanism of action of MPG, we showed that MPG decreased the transcript levels of ICAM-1, VCAM-1 and E-selectin genes. Using electrophoretic mobility shift assay (EMSA) and western blot analyses, we demonstrated that MPG significantly blocked both the TNFα-induced translocation and activation of nuclear transcription factor-κB (NF-κB). Thus, MPG could be useful as a novel lead molecule for developing future anti-inflammatory agents.

Lewis acid-catalyzed one-pot, three-component route to chiral 3,3'-bipyrroles.

3,3'-Bipyrroles 3 could be synthesized using a double Michael addition reaction involving diaroyl acetylene 1 and the appropriate 1,3-dicarbonyls 2 using ammonium acetate as a nitrogen source. The axial chirality of bipyrrole was anticipated from the X-ray crystal structure and DFT calculations and confirmed by separating the racemates on a chiral column and subsequent CD spectra of the enantiomers. The absolute configuration of the enantiomers was achieved by theoretical CD spectra calculation using the ZINDO method.