Hepatoprotective and Antioxidant Capacity of Clerodendrum paniculatum Flower Extracts against Carbon Tetrachloride-Induced Hepatotoxicity in Rats

The aim of the presented work involves the isolation, characterization, and evaluation of hepatoprotective potential of Clerodendrum paniculatum flower extracts. For this purpose, petroleum ether, chloroform, ethyl acetate, alcohol, and water extracts of C. paniculatum flower were screened for the flavonoid and phenolic content and quantified. Various antioxidant activity assays including 2,2′-diphenyl-1-picrylhydrazyl (DPPH), nitric oxide (NO) radical scavenging, 2,2-azinobis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), and reducing ability were carried out. Of the above methods, the alcoholic extract exhibited high antioxidant potential and was selected further for the hepatoprotective evaluations. Hepatoprotective evaluation of the alcoholic extract was carried out for carbon tetrachloride (CCl4)-intoxicated model systems. Enzymes associated with liver functions were estimated, and histopathological evaluations were carried out to monitor the liver architecture. Prominently, reduced levels of various associated enzymes along with increased protein content were observed when the liver specimen was pretreated with the extract. Moreover, the liver architecture was almost comparable to that of the normal control group. The column chromatographic analysis of the extract revealed 13 fractions to possess high phenolics and flavonoid contents. The best two fractions were identified for in vitro hepatoprotective evaluation in the goat liver model. Furthermore, the GC–MS analyses of the fractions were carried out followed by a library search, to identify the constituents responsible for the hepatoprotective activity which revealed the presence of four major constituentspilocarpine, glyceric acid, pangamic acid, and gallic acid. An in vitro hepatoprotective study of the isolated fractions showed better activity compared to the whole alcoholic extract, and the results were comparable to the normal group taken as a control. The investigations with an in vitro model suggest that the isolated fraction with rich flavonoid content showed better hepatoprotective activity. GC–MS analysis of the fractions that displayed good hepatoprotective activity suggested the presence of pilocarpine, glyceric acid, pangamic acid, and gallic acid, while HPTLC analysis revealed the presence of quercetin

One-Pot, Telescopic Approach for the Chemoselective Synthesis of Substituted Benzo[<i>e</i>]pyrido/pyrazino/pyridazino[1,2‑<i>b</i>][1,2,4]thiadiazine dioxides and Their Significance in Biological Systems

The one-pot telescopic approach has been developed for the chemoselective synthesis of substituted benzo­[e]­pyrido/pyrazino/pyridazino­[1,2-b]­[1,2,4]­thiadiazine dioxides using readily available 2-aminopyridines/pyrazines/pyridazine and 2-chloro benzene sulfonyl chloride. This one-pot procedure involves the chemoselective sulfonylation of 2-aminopyridines/pyrazines/pyridazine with 2-chloro benzene sulfonyl chloride followed by a Cu­(I)-catalyzed Ullmann-type C–N coupling reaction to obtain benzo­[e]­pyrido/pyrazino/pyridazino­[1,2-b]­[1,2,4]­thiadiazine dioxides with broad substrate scope and high functional group tolerance. The synthetic sequence merges well with the nucleophilic attack on the 2-amino group of pyridines/pyrazines/pyridazines on the 2-chloro benzene sulfonyl chloride, followed by Cu­(I)-catalyzed ipso chloro displacement to C–N bond formation resulting in a more modular and straightforward approach. Moreover, the biological significance of the synthesized benzothiadiazine dioxides was evaluated by following their ability to bind to protein macromolecules and their anti-inflammatory activity

One-Pot, Telescopic Approach for the Chemoselective Synthesis of Substituted Benzo[<i>e</i>]pyrido/pyrazino/pyridazino[1,2‑<i>b</i>][1,2,4]thiadiazine dioxides and Their Significance in Biological Systems

The one-pot telescopic approach has been developed for the chemoselective synthesis of substituted benzo­[e]­pyrido/pyrazino/pyridazino­[1,2-b]­[1,2,4]­thiadiazine dioxides using readily available 2-aminopyridines/pyrazines/pyridazine and 2-chloro benzene sulfonyl chloride. This one-pot procedure involves the chemoselective sulfonylation of 2-aminopyridines/pyrazines/pyridazine with 2-chloro benzene sulfonyl chloride followed by a Cu­(I)-catalyzed Ullmann-type C–N coupling reaction to obtain benzo­[e]­pyrido/pyrazino/pyridazino­[1,2-b]­[1,2,4]­thiadiazine dioxides with broad substrate scope and high functional group tolerance. The synthetic sequence merges well with the nucleophilic attack on the 2-amino group of pyridines/pyrazines/pyridazines on the 2-chloro benzene sulfonyl chloride, followed by Cu­(I)-catalyzed ipso chloro displacement to C–N bond formation resulting in a more modular and straightforward approach. Moreover, the biological significance of the synthesized benzothiadiazine dioxides was evaluated by following their ability to bind to protein macromolecules and their anti-inflammatory activity

Microwave-Assisted Linear Approach Toward Highly Substituted Benzo[<i>d</i>]oxazol-5-yl-1<i>H</i>-benzo[<i>d</i>]imidazole on Ionic Liquid Support

A novel and efficient diversity-oriented synthetic approach was employed to access the benzo­[<i>d</i>]­oxazol-5-yl-1<i>H</i>-benzo­[<i>d</i>]­imidazole on ionic liquid support, which helps to absorb microwave irradiation. In this paper, we successfully coupled 4-hydroxy-3-nitrobenzoic acid onto ionic liquid-immobilized <i>o</i>-phenylenediamine, which subsequently underwent an acid mediated, ring closure reaction leading to benzimidazole derivatives. After hydrogenation of the nitro group to an amine, the resulting ionic liquid conjugate was reacted with 1,1-thiocarbonyldiimidazols to yield an ionic liquid tagged-benzoxazol. Final skeletal diversity of the present scaffold was further achieved by S-alkylation with alkyl and aryl bromides. The benzo­[<i>d</i>]­oxazol-5-yl-1<i>H</i>-benzo­[<i>d</i>]­imidazole was finally cleaved smoothly from the ionic liquid support with sodium methoxide in methanol under microwave irradiation. This methodology has provided access to a small, diverse library by straightforward and simple operations and could be applied readily in various drug discovery programs

Aqueous Phase Synthesis of Palladium Tripod Nanostructures for Sonogashira Coupling Reactions

In this work, palladium tripod nanocrystals have been synthesized by mixing an aqueous solution of cetyltrimethylammonium bromide (CTAB) surfactant, Na2PdCl4, copper acetate, and ascorbic acid at 30 °C for 3 h. Addition of a small amount of copper ion source is critical to the formation of these tripods with a pod length reaching 100 nm. The incorporation of Cu atoms into the Pd tripods has been verified. The entire Pd tripod is single-crystalline with their branches growing along the [111] and [200] directions. Formation of side branches can be observed in some tripods. Triangular nanoplates are initially formed and evolved into the tripod structure in 20–30 min of reaction. Further growth leads to elongation of the pods. The large Pd tripods can serve as active and recyclable catalysts for a broad range of Sonogashira coupling reactions in water using a variety of aromatic halides containing electron-donating and -withdrawing substituents

Microwave Controlled Reductive Cyclization: A Selective Synthesis of Novel Benzimidazole-alkyloxypyrrolo[1,2‑<i>a</i>]quinoxalinones

An efficient cascade synthesis of novel benzimidazole linked alkyloxypyrrolo­[1,2-<i>a</i>]­quinoxalinones was explored on soluble polymer support under microwave irradiation. Two exclusive protocols have been developed for the partial and full reductive cyclization by controlling the microwave energy. Commencing from the same substrate, ortho nitro pyrrol carboxylates, <i>N</i>-hydroxy pyrroloquinoxalinones were obtained by partial reductive cyclization (60 °C, 7 min), and the synthesis of pyrroloquinoxalinones was accomplished by full reductive cyclization (85 °C, 12 min). This method represents the first synthesis of <i>N</i>-hydroxy pyrroloquinoxalinones using Pd/C and ammonium formate as reducing agents. Further employing a variety of alkyl bromides, the obtained pyrroloquinoxalinones were transformed to their corresponding O- and N-alkylated analogues to deliver the diversified, novel molecular entities

Rapid Construction of an Imidazo[4,5‑<i>b</i>]pyridine Skeleton from 2‑Chloro-3-nitropyridine via Tandem Reaction in H₂O‑IPA Medium

A highly efficient, clean, and simple procedure for the synthesis of a privilege imidazo­[4,5-<i>b</i>]­pyridine scaffold from 2-chloro-3-nitropyridine in combination with environmentally benign H₂O-IPA as a green solvent is presented. The scope of the novel method has been demonstrated through the tandem sequence of S_NAr reaction with substituted primary amines followed by the in situ nitro group reduction and subsequent heteroannulation with substituted aromatic aldehydes to obtain functionalized imidazo­[4,5-<i>b</i>]­pyridines with only one chromatographic purification step. The synthesis pathway appears to be green, simple, and superior compared with other already reported procedures, with the high abundance of reagents and great ability in expanding the structural diversity

Multicomponent Solvent-Free Synthesis Of Benzimidazolyl Imidazo[1,2‑<i>a</i>]‑pyridine Under Microwave Irradiation

A novel one-pot, three-component reaction employing variously substituted benzimidazole-linked amino pyridines, aldehydes, and isonitriles catalyzed by scandium­(III) triflate under solvent-free conditions were accomplished. This new synthetic methodology facilitates the rapid generation of intricate molecular frameworks in three-dimensional fashion leading to benzimidazole-imidazo­[1,2-<i>a</i>] pyridines. This approach is envisioned as an environmentally benign process and a simple operation to the biological interesting compounds. The present synthetic sequence permits the introduction of three points of structural diversity to expand chemical space with high purity and excellent yields

Formation of Diverse Supercrystals from Self-Assembly of a Variety of Polyhedral Gold Nanocrystals

Cubic, rhombic dodecahedral, octahedral, and corner-truncated octahedral gold nanocrystals with sizes of tens of nanometers have been used as building blocks to form micrometer-sized supercrystals by slowly evaporating a water droplet on a substrate placed in a moist environment. Drying the droplet at 90 °C was found to yield the best supercrystals. Supercrystals were evenly distributed throughout the entire substrate surface originally covered by the droplet. Diverse supercrystal morphologies have been observed. Nanocubes formed roughly cubic supercrystals. Rhombic dodecahedra were assembled into truncated triangular pyramidal supercrystals. Rhombic dodecahedral, octahedral, and hexapod-shaped supercrystals were generated through the assembly of octahedra. Corner-truncated octahedra formed tetrapod-shaped supercrystals at room temperature, but octahedral, truncated triangular pyramidal, and square pyramidal supercrystals at 90 °C. Nanocrystal assembly was found to be strongly shape-guided. Expulsion of excess surfactant to the surfaces of supercrystals suggests that responsive adjustment of surfactant concentration during particle assembly mediates supercrystal formation. Transmission X-ray microscopy and optical microscopy have been employed to follow the supercrystal formation process. Surprising rotational water current near the droplet perimeter carrying the initially formed supercrystals has been observed. Supercrystals appear to grow from the edge of the droplet toward the central region. Supercrystals assembled from octahedra inherently contain void spaces and possibly connected channels. The mesoporosity of these supercrystals was confirmed by infiltrating H₂PdCl₄ into the supercrystal interior and reducing the precursor to form Pd nanoparticles. The embedded Pd particles can still catalyze a Suzuki coupling reaction, demonstrating the application of these supercrystals for molecular transport, sensing, and catalysis

Altered Levels of Long NcRNAs Meg3 and Neat1 in Cell And Animal Models Of Huntington’s Disease

Altered expression levels of protein-coding genes and microRNAs have been implicated in the pathogenesis of Huntington’s disease (HD). The involvement of other ncRNAs, especially long ncRNAs (lncRNA), is being realized recently and the related knowledge is still rudimentary. Using small RNA sequencing and PCR arrays we observed perturbations in the levels of 12 ncRNAs in HD mouse brain, eight of which had human homologs. Of these, Meg3, Neat1, and Xist showed a consistent and significant increase in HD cell and animal models. Transient knock-down of Meg3 and Neat1 in cell models of HD led to a significant decrease of aggregates formed by mutant huntingtin and downregulation of the endogenous Tp53 expression. Understanding Meg3 and Neat1 functions in the context of HD pathogenesis is likely to open up new strategies to control the disease.</p