Design,synthesis and biological evaluation of 5-(2-(4-(substituted benzo[d]isoxazol-3-yl)piperazin-1-yl)acetyl)indolin-2-one and 5-(2-(4-substitutedpiperazin-1-yl)acetyl)indolin-2-one analogues as novel anti-tubercular agents

A series of thirty-six novel 5-(2-(4-(benzo[d]isoxazol-3-yl)piperazin-1-yl)acetyl)indolin-2-one and 5-(2-(4-substitutedpiperazin-1-yl)acetyl)indolin-2-one analogues were synthesized, characterized and screened for their in vitro anti-tubercular activity against Mycobacterium tuberculosis H37Rv strain. These compounds exhibited minimum inhibitory concentration between 1.56 and 50 μg/mL. Among these derivatives, compounds 10c, 10d, 10j, 10o and 10v (MIC 6.25 μg/mL) displayed moderate activity, while compounds 10e, 10l, 10q, 10w,10x, 12d, 12e and 12i (MIC 3.12 μg/mL) showed good anti-tubercular activity and compounds 10f, 10k, 10p, 10r, 12f, 12j and 12k (MIC 1.56 μg/mL) exhibited excellent anti-tubercular activity. In addition, MTT assay was accomplished on the active analogues of the series against mouse macrophage (RAW 264.7) cells to evaluate the cytotoxic effect of the newly synthesized compounds and selectivity index of the compounds was determined.     

Enantiomeric separation of a melatonin agonist Ramelteon using amylose-based chiral stationary phase

A new simple isocratic chiral liquid chromatographic method was developed for the enantiomeric purity of Ramelteon[(S)-N-[2-(1,6,7,8-tetrahydro-2H-indeno[5,4-b]furan-8-yl) ethyl]-propionamide], a melatonin agonist in bulk drugs. The chromatographic separation was achieved on Chiralpak AD-H, 250 mm × 4.6 mm, 5 μm column using a mobile phase system consisting of n-hexane, ethanol and methanesulfonic acid in the ratio of 900:100:0.1 (v/v/v). The mobile phase was pumped on the column at the flow rate of 1 mL min^?1. Addition of methane sulfonic acid in the mobile phase enhanced chromatographic efficiency and resolution between the enantiomers. The resolution between the enantiomers was found to be more than four. The developed method was subsequently validated and proved to be accurate and precise. The experimentally established limit of detection and quantification of (R)-enantiomer were found to be 25.5 and 77.2 ng ml^?1, respectively, for 20 μl injection volumes. The percentage recovery of (R)-enantiomer was ranged from 98.5 to 101.9 in bulk drug samples of Ramelteon. The stability of Ramelteon sample in analytical solution was checked for about 48 h at room temperature and was found to be stable for about 48 h. The proposed method was found to be suitable and accurate for the quantitative determination of (R)-enantiomer in drug substance.     

Intramolecular O‐arylation using nano‐magnetite supported N‐heterocyclic carbene‐copper complex with wingtip ferrocene

Nano‐magnetite supported N‐heterocyclic carbene‐copper complex with wingtip ferrocene has been prepared via multi‐step procedure. The complex has been characterized by various analytical techniques such as fourier transform infrared (FT‐IR), fourier transform Raman (FT‐Raman), X‐ray photoelectron spectroscopy (XPS), X‐ray diffraction (XRD), transmission electron microscopy (TEM) and vibrating sample magnetometer (VSM) analysis. The catalytic activity of the complex has been exploited in intramolecular O‐arylation of o‐iodoanilides under heterogeneous conditions. The complex could be successfully recycled up to twelve consecutive cycles.     

Sulfated tin oxide (SO4−2/SnO2): an efficient heterogeneous solid superacid catalyst for the facile synthesis of 2,3-dihydroquinazolin-4(1H)-ones

Research on Chemical Intermediates - A novel methodology for the facile synthesis of 2,3-dihydroquinazolin-4(1H)-ones by using sulfated tin oxide (SO4?2/SnO2) as a heterogeneous solid...     

Facile synthesis of ferrocenylamines in aqueous hydrotropic solution using microwaves

Microwave-assisted synthesis of secondary and tertiary ferrocenylamines is achieved by using an amine exchange reaction between ferrocenylmethyltrimethyl ammonium iodide and aryl amines in aqueous hydrotropic solution. The synthesis proceeds in excellent yields within short reaction times.     

A Highly Thermostable Alkaline Cellulase-Free Xylanase from Thermoalkalophilic <Emphasis Type="Italic">Bacillus</Emphasis> sp. JB 99 Suitable for Paper and Pulp Industry: Purification and Characterization

A highly thermostable alkaline xylanase was purified to homogeneity from culture supernatant of Bacillus sp. JB 99 using DEAE-Sepharose and Sephadex G-100 gel filtration with 25.7-fold increase in activity and 43.5% recovery. The molecular weight of the purified xylanase was found to be 20 kDA by SDS-PAGE and zymogram analysis. The enzyme was optimally active at 70 °C, pH 8.0 and stable over pH range of 6.0–10.0.The relative activity at 9.0 and 10.0 were 90% and 85% of that of pH 8.0, respectively. The enzyme showed high thermal stability at 60 °C with 95% of its activity after 5 h. The K _m and V _max of enzyme for oat spelt xylan were 4.8 mg/ml and 218.6 μM min⁻¹ mg⁻¹, respectively. Analysis of N-terminal amino acid sequence revealed that the xylanase belongs to glycosyl hydrolase family 11 from thermoalkalophilic Bacillus sp. with basic pI. Substrate specificity showed a high activity on xylan-containing substrate and cellulase-free nature. The hydrolyzed product pattern of oat spelt xylan on thin-layer chromatography suggested xylanase as an endoxylanase. Due to these properties, xylanase from Bacillus sp. JB 99 was found to be highly compatible for paper and pulp industry.     

1,2-Shift in the anodic oxidation of aromatic compounds

The 1,2-shift observed during oxidation of organic substrates can arise by involvement of cation radicals.     

Azo compounds with different sized fluorophores and characterization of their photophysical properties based on trans to cis conformational change

We synthesized fluorophores of different sizes attached to azo derivatives, such as thiophene-, naphthalene-, anthracene-, and pyrene-based azo compounds, and studied their photophysical properties. The compounds exhibited strong color and intensity changes in absorption and emission during the structural change from trans to cis, which also resulted in a large Stokes shift and a difference in quantum yield. Depending on their size, the compounds had different rates of transformation from the trans to cis structure: less conjugated (smaller) fluorophore azo compounds showed higher transition rates than more conjugated (larger) ones.     

NO-NSAIDs. Part 3: nitric oxide-releasing prodrugs of non-steroidal anti-inflammatory drugs

In continuation of our efforts to discover novel nitric oxide-releasing non-steroidal anti-inflammatory drugs (NO-NSAIDs) as potentially "Safe NSAIDs," we report herein the design, synthesis and evaluation of 21 new NO-NSAIDs of commonly used NSAIDs such as aspirin, diclofenac, naproxen, flurbiprofen, ketoprofen, sulindac, ibuprofen and indomethacin. These prodrugs have NO-releasing disulfide linker attached to a parent NSAID via linkages such as an ester (compounds 9-16), a double ester (compounds 17-24), an imide (compounds 25-30) or an amide (compounds 31-33). Among these NO-NSAIDs, the ester-containing NO-aspirin (9), NO-diclofenac (10), NO-naproxen (11), and the imide-containing NO-aspirin (25), NO-flurbiprofen (27) and NO-ketoprofen (28) have shown promising oral absorption, anti-inflammatory activity and NO-releasing property, and also protected rats from NSAID-induced gastric damage. NO-aspirin compound 25, on further co-evaluation with aspirin at equimolar doses, exhibited comparable dose-dependent pharmacokinetics, inhibition of gastric mucosal prostaglandin E(2) (PGE(2)) synthesis and analgesic properties to those of aspirin, but retained its gastric-sparing properties even after doubling its oral dose. These promising NO-NSAIDs could therefore represent a new class of potentially "Safe NSAIDs" for the treatment of arthritic pain and inflammation.