Synthesis, Spectral Characterization and Photoluminescence of 3-chloro-6-methoxy-2-(methylsulfanyl)quinoxaline in Different Solvents: An Experimental and Theoretical Investigation Using DFT.

In the present work, we synthesized 3-chloro-6-methoxy-2-(methyl sulfanyl) quinoxaline (3MSQ) using a microwave-assisted synthesis method. The physicochemical structural analysis of the synthesized compound utilizing 1H-NMR, 13C-NMR, and FT-IR spectroscopy techniques. The photophysical properties of 3MSQ was examined through absorption and fluorescence spectroscopy. Spectroscopic analyses revealed a bathochromic shift in both absorption and fluorescence spectra, attributed to the π → π* transition. Ground and excited state dipole moments was experimentally determined using the solvatochromic shift method, employing various correlations such as Lippert's, Bakhshiev's, Kawski-Chamma-Viallet's equations, and solvent polarity parameters. Our findings indicate that the excited state dipole moments exceed those of the ground state, suggesting increased polarity in the excited state. Further, the while detailed bond length, bond angles, dihedral angles, Mulliken charge distribution, ground state dipole moments and HOMO-LUMO energy gap estimated through ab initio computations using Gaussian-09W. The value of energy band gap obtained from both the methods are in good agreement. Furthermore, employing DFT computational analysis, we identified reactive centers such as electrophilic and nucleophilic sites using molecular electrostatic potential (MESP) 3D plots. Additionally, CIE chromaticity analysis was performed to understand the photoluminescent properties of 3MSQ. The insights derived from these analyses contribute to a better understanding of the molecule's electronic structure, photophysical properties, and solute-solvent interactions, thus providing valuable information regarding its behaviour and characteristics under diverse conditions. These results contribute to a comprehensive understanding of the molecular structure and properties of 3-chloro-6-methoxy-2-(methyl sulfanyl) quinoxaline (3MSQ).

Purification and characterization of acid phosphatase from Macrotyloma uiflorum seeds.

Acid phosphatases play a crucial role in food processing industries to reduce phosphate content of food. Here in acid phosphatase from the seeds of Macrotyloma uniflorum has been purified to homogeneity using UNOsphere-S cation exchange chromatography followed by gel filtration with 81.85 fold purification. Molecular weight of purified enzyme was 55,000 (± 1040) Daltons under physiological conditions. It was a heterodimer of subunits having molecular weights 27,093 and 28,241 Daltons as determined by MALDI-TOF analysis. The optimum pH and temperature for the purified enzyme was 5.0 and 50 °C respectively. The enzyme was stable in the pH range 3.5-5.5 and showed temperature stability up to 60 °C. Substrate specificity of enzyme was checked with different substrates namely, p-nitrophenyl phosphate (p-NPP), ATP, ADP, glucose 6-phosphate, glucose-1-phosphate, fructose 6-phosphate, phenyl phosphate, α-naphthyl-phosphate, pyridoxyl phosphate and ß-glycerophosphate. Enzyme showed high substrate specificity towards p-NPP, phenyl phosphate, ATP and α-naphthyl phosphate. Km and Vmax of enzyme were found to be 0.934 mM and 1.333 mM/min respectively with respect to p-NPP as a substrate. Chemical modification studies showed that tryptophan was present at the active site of the enzyme.

An in-vitro study to compare the temperature rise in the pulp chamber by direct method using three different provisional restorative materials.

STATEMENT OF PROBLEM: The provisional restorative materials in fixed prosthodontics are basically bis-GMA resins which releases exothermic temperature while polymerization which can damage the pulp. Intrapulpal temperature exceeding 42.5°C found to result in irreversible damage to the pulp. The remaining thickness of dentine after tooth preparation control the conduction of heat released by the resins. PURPOSE: (1) To quantify the temperature changes in the pulp chamber using different provisional restorative materials. (2) To evaluate the peak temperature time of different materials used. (3) To compare the intrapulpal temperature changes with a variation in the width of the finish line. METHODOLOGY: Two intact mandibular molars were selected and designated as Specimen A and B. Tooth preparation was done to prepare a finish line of 1.2 mm and 1 mm width, respectively. Three provisional restorative materials were considered and they were grouped as Group I-Cool temp, Group II-Protemp-4, Group III-Integrity. A J thermocouple probe was placed into the pulp chamber to determine the rise in temperature. The temperature was recorded during polymerization at 30-s intervals until the peak temperature was reached. The same procedure was repeated for fabricating remaining provisional crowns. A total of 45 provisional crowns were fabricated for each specimen. RESULTS: Kruskal-Wallis test revealed that there was a significant difference in the temperature changes associated with the provisional restorative materials used. All the three provisional restorative materials were compared for 1.2 mm and 1 mm wide finish line. Integrity produced the highest temperature rise and the maximum temperature recorded was 40.2°C in 1.2 mm wide finish line. However, for a 1 mm wide finish line, Protemp-4 produced the highest temperature rise and the maximum temperature recorded was 40.3°C. It was observed that peak temperatures with Specimen B were more when compared with Specimen A. CONCLUSION: Cool temp showed least temperature rise in the pulp chamber. The order of rise in intrapulpal temperature in tested provisional materials using direct technique would be Cool temp, Integrity, and Protemp-4.

α-Geminal dihydroxymethyl piperidine and pyrrolidine iminosugars: synthesis, conformational analysis, glycosidase inhibitory activity, and molecular docking studies.

The Jocic-Reeve and Corey-Link type reaction of dichloromethyllithium with suitably protected 5-keto-hexofuranoses followed by treatment with sodium azide and sodium borohydride reduction gave 5-azido-5-hydroxylmethyl substituted hexofuranoses 7a-c with required geminal dihydroxymethyl group. Removal of protecting groups and converting the C-1 anomeric carbon into free hemiacetal followed by intramolecular reductive aminocyclization with in situ generated C5-amino functionality afforded corresponding 5C-dihydroxymethyl piperidine iminosugars 2a-c. Alternatively, removal of protecting groups in 7b and 7c and chopping of C1-anomeric carbon gave C2-aldehyde that on intramolecular reductive aminocyclization with C5-amino gave 4C-dihydroxymethyl pyrrolidine iminosugars 1b and 1c, respectively. On the basis of the (1)H NMR studies, the conformations of 2a/2b were assigned as (4)C(1) and that of 2c as (1)C(4). The glycosidase inhibitory activities of all five iminosugars were studied with various glycosidase enzymes and compared with natural d-gluco-1-deoxynojirimycin (DNJ). All the five compounds were found to be potent inhibitors of rice α-glucosidase with K(i) and IC(50) values in the nanomolar concentration range. Iminosugars 2b and 1b were found to be more potent inhibitors than their parent iminosugar. These results were substantiated by in silico molecular docking studies.

Bicyclic amino acid-carbohydrate-conjugates as conformationally restricted hydroxyethylamine (HEA) transition-state isosteres.

This communication describes a general synthetic route to bicyclic amino acid-carbohydrate-conjugates, which would be useful as conformationally restricted hydroxyethylamine (HEA) transition-state isosteres. The synthesis was achieved in 12 steps starting from D-glucose. The striking features of this system are the bicyclic rigid core displaying an α-amino acid side chain and hydroxyethylamine moiety--both of which would be potentially important for receptor interactions, leading to various biomedical responses, as described in the literature. Crystal structure investigation suggested extensive intermolecular hydrogen-bonding interactions in this system, involving the backbone amide and hydroxyl groups.

Synthesis of new six- and seven-membered 1-N-iminosugars as promising glycosidase inhibitors.

New six- and seven-membered 1-N-iminosugars were prepared from d-glucose by the stereoselective Michael addition of nitromethane to d-glucose derived α,ß-unsaturated ester A followed by one pot reduction of nitro/ester functionality and subsequent amine protection to get N-Cbz protected aminol 6. Hydrolysis of 1,2-acetonide and reductive aminocyclization gave seven membered 1-N-iminosugar 5b. While, hydrolysis of 1,2-acetonide followed by NaIO(4) oxidative cleavage and hydrogenation using 10% Pd(OH)(2)/C, H(2) gave six membered 1-N-iminosugar 4a; the hydrogenation using 10% Pd/C-H(2) however, gave N-methyl substituted 1-N-iminosugar 4b. The hydrochloride salts of 4a/4b and 5b were found to be specific α-galactosidase and moderate α-glucosidae inhibitors, respectively, in micro molar range.

Involvement of opioid, adenosine and 5-HT(3) receptors in antinociceptive effects of an ayurvedic polyherbal formulation.

OBJECTIVE: The present study was undertaken to evaluate the antinociceptive effects of an ayurvedic polyherbal formulation in rats and mice employing the tail immersion test and acetic acid-induced writhing test, respectively. MATERIALS AND METHODS: With the tail immersion method, rats received two different doses (270 and 405 mg/kg BW, p.o.) of a formulation, pethidine (5.4 mg/kg BW, p.o.) as a reference standard and the combination of the higher dose of the formulation with naloxone (2 mg/kg, i.p.), an opioid receptor antagonist, and caffeine (16 mg/kg, i.p.), used as an adenosine receptor antagonist. In the acetic acid-induced writhing test, mice received two different doses (390 and 585 mg/kg, BW, p.o.) of formulation, diclofenac sodium (15 mg/kg, BW, p.o.) as a reference standard and the combination of the higher dose of the polyherbal formulation with ondansetron (0.5 mg/kg, i.p.), a serotonin receptor antagonist. RESULTS: The polyherbal formulation (405 mg/kg) exhibited a significant (p < 0.01) antinociceptive effect using the tail immersion method. In the acetic acid-induced writhing test, the formulation showed significant (p < 0.01) dose-dependent activity. The antinociceptive effect of the polyherbal formulation apparently involved an opiate-like mechanism, since its antinociceptive action was attenuated by naloxone pretreatment. In addition, antinociceptive activity was attenuated by caffeine and reversed by ondansetron pretreatment. CONCLUSION: Our data suggest that the polyherbal formulation possessed centrally and peripherally mediated antinociceptive properties. The activity could be mediated through opioid, adenosine, and serotonin receptors and via inhibition of cyclo-oxygenase- and/or lipoxygenase-dependent pathways.

Antidiabetic potential of α-amylase inhibitor from the seeds of Macrotyloma uniflorum in streptozotocin-nicotinamide-induced diabetic mice.

CONTEXT: Macrotyloma uniflorum (Lam.) Verdc. (Leguminosae) seeds, known as the poor man's pulse crop in India, have been used as a food and also used in the traditional method for treatment of kidney stones, diabetes, obesity, etc. OBJECTIVE: To investigate the antidiabetic effect of α-amylase inhibitor isolated from the seeds of Macrotyloma uniflorum seeds in streptozotocin-nicotinamide induced diabetic mice. MATERIALS AND METHOD: α-Amylase inhibitor was purified using a carboxymethyl cellulose (CMC) column. Kinetic studies were done using mouse pancreatic and human salivary α-amylase. Its antidiabetic effect was studied in streptozotocin-nicotinamide-induced diabetic mice. Biochemical parameters such as serum total cholesterol, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels were determined. Histopathological investigation was performed on the pancreas, kidney, and liver tissue samples. RESULTS: Macrotyloma uniflorum α-amylase inhibitor (MUAI) inhibited both the mouse pancreatic and human salivary α-amylase in a non-competitive manner with K(i) values of 11 and 8.8 µM and IC(50) value of 30 and 12.5 µg/mL, respectively. It decreased the serum glucose level in the treated diabetic mice. Histological findings suggested minimum pathological changes in the treated diabetic mice as compared to the diabetic control. DISCUSSION AND CONCLUSION: The results suggest that MUAI has an antihyperglycemic activity and therefore can be used in the dietary treatment of non-insulin dependent diabetes mellitus.

Intramolecular reductive cyclization strategy to the synthesis of (-)-6-methyl-3-hydroxy-piperidine-2-carboxylic acid, (+)-6-methyl-(2-hydroxymethyl)-piperidine-3-ol and their glycosidase inhibitory activity.

The first stereoselective synthesis of (2S,3R,6S)-6-methyl-3-hydroxy-piperidine-2-carboxylic acid (-)-6 and (2R,3R,6S)-6-methyl-(2-hydroxymethyl)-piperidine-3-ol (+)-7 was achieved starting from readily available d-glucose in 14 steps with 17% overall yield for both the compounds. The key feature of the present strategy includes the Wittig-olefination for the preparation of required conjugated keto-azide 9 and construction of 2,3,6-trisubstituted piperidine skeleton 11 by applying intramolecular reductive cyclization of conjugated keto-azide intermediate. The glycosidase inhibitory activity of compounds 6 and 7 towards several glycosidases has been evaluated.

Nootropic activity of Celastrus paniculatus seed.

The effect of Celastrus paniculatus Willd. (Celastraceae) seed aqueous extract on learning and memory was studied using elevated plus maze and passive avoidance test (sodium nitrite induced amnesia rodent model). The aqueous seed extract was administered orally in two different doses to rats (350 and 1050 mg/kg) and to mice (500 and 1500 mg/kg). The results were compared to piracetam (100 mg/kg, p.o.) used as a standard drug. Chemical hypoxia was induced by subcutaneous administration of sodium nitrite (35 mg/kg), immediately after acquisition training. In elevated plus maze and sodium nitrite-induced amnesia model, Celastrus paniculatus extract has showed statistically significant improvement in memory process when compared to control. The estimation of acetylcholinesterase enzyme in rat brain supports the plus maze and passive avoidance test by reducing acetylcholinesterase activity which helps in memory performance. The study reveals that the aqueous extract of Celastrus paniculatus seed has dose-dependent cholinergic activity, thereby improving memory performance. The mechanism by which Celastrus paniculatus enhances cognition may be due to increased acetylcholine level in rat brain.

A versatile access to calystegine analogues as potential glycosidases inhibitors.

An efficient metathetic strategy and nitrone chemistry have been suitably tethered to construct 8-azabicyclo[3.2.1]octanes as versatile precursors for the synthesis of several calystegine analogues. This synthetic strategy relies on the ability of mannose-derived nitrone to undergo a highly stereoselective nucleophilic addition of various Grignard reagents to access syn orientation of alkenes, which then smoothly undergo ring-closing metathesis (RCM) to provide this framework. These RCM products 18 and 20 have been successfully used as advance precursors to synthesize many calystegine analogues (27, 36, 38, 40, 43, and 44) either by syn-dihydroxylation or by hydrogenation and followed by global deprotection. Interestingly, both compounds 36 and 40 exhibited significant noncompetitive inhibition against alpha-mannosidase and N-acetyl-beta-D-glucosaminidase.

Leaf Whorl Inoculation Method for Screening Sugarcane Rust Resistance.

Brown rust, caused by Puccinia melanocephala, and orange rust, caused by P. kuehnii, are agronomically important diseases of sugarcane in Florida. Cultivar resistance is the best means of controlling these diseases. Natural infection has been the primary means of assessing resistance in sugarcane cultivars against rusts; unfortunately, natural infection is not always efficient in identifying resistant cultivars due to variable environmental conditions. Therefore, a more reliable screening method is needed to effectively select resistant genotypes. An inoculation technique was evaluated for identification of brown and orange rust resistance in sugarcane cultivars. Inoculations were performed in the field by placing a 0.5-ml urediniospore suspension in the leaf whorl of three individual sugarcane stalks per plant using a pipette. Symptoms developed on leaves of all the susceptible cultivars after 4 weeks, and appeared as a band of pustules. Plants were rated for their reaction to rust 4 weeks after inoculation. The optimum concentrations of inoculum for expression of brown and orange rust symptoms were determined. The most severe brown rust and orange rust symptoms were observed using inoculum containing 105 and 104 urediniospores/ml, respectively. Clones in several stages of the Canal Point breeding program were screened for their rust reaction by leaf whorl inoculation. The technique enabled rapid screening of a large number of cultivars in field plantings using a small amount of inoculum and limited man hours.

Isolation of nucleotide binding site-leucine rich repeat and kinase resistance gene analogues from sugarcane (Saccharum spp.).

BACKGROUND: Resistance gene analogues (RGAs) have been isolated from many crops and offer potential in breeding for disease resistance through marker-assisted selection, either as closely linked or as perfect markers. Many R-gene sequences contain kinase domains, and indeed kinase genes have been reported as being proximal to R-genes, making kinase analogues an additionally promising target. The first step towards utilizing RGAs as markers for disease resistance is isolation and characterization of the sequences. RESULTS: Sugarcane clone US01-1158 was identified as resistant to yellow leaf caused by the sugarcane yellow leaf virus (SCYLV) and moderately resistant to rust caused by Puccinia melanocephala Sydow & Sydow. Degenerate primers that had previously proved useful for isolating RGAs and kinase analogues in wheat and soybean were used to amplify DNA from sugarcane (Saccharum spp.) clone US-01-1158. Sequences generated from 1512 positive clones were assembled into 134 contigs of between two and 105 sequences. Comparison of the contig consensuses with the NCBI sequence database using BLASTx showed that 20 had sequence homology to nuclear binding site and leucine rich repeat (NBS-LRR) RGAs, and eight to kinase genes. Alignment of the deduced amino acid sequences with similar sequences from the NCBI database allowed the identification of several conserved domains. The alignment and resulting phenetic tree showed that many of the sequences had greater similarity to sequences from other species than to one another. CONCLUSION: The use of degenerate primers is a useful method for isolating novel sugarcane RGA and kinase gene analogues. Further studies are needed to evaluate the role of these genes in disease resistance.

Simplified purification approach of urinary neutrophil gelatinase-associated lipocalin by tangential flow filtration and ion exchange chromatography.

This investigation reports a simplified approach for the purification of urinary siderocalin known as neutrophil gelatinase-associated lipocalin (NGAL). Urinary NGAL was purified by tangential flow filtration and ion exchange chromatography. Isolated NGAL was analyzed by SDS-PAGE, immunoblotting and mass spectrometry (MS). The relative molecular mass of NGAL is 23674Da. Peptide mass fingerprinting of the purified NGAL yielded peptides that partially matched with known sequence of P80188 (NGAL_HUMAN). The tryptic digestion profile of isolated NGAL infers that it may be unique and additive molecule in the dictionary of urinary proteins. This is the first report of purification and validation of urinary NGAL from large volume sample by using tangential flow filtration and peptide sequencing respectively. This cost-effective and simplified approach to purification of NGAL, together with the easy availability of urine sample makes the large-scale production of NGAL possible, allowing exploration of various bioclinical as well as biodiagnostic applications.

Halogenated D-xylono-δ-lactams: synthesis and enzyme inhibition study.

A concise synthesis of four C-3 fluoro/chloro-D-xylono-δ-lactams 3/4 has been reported. The methodology involves Corey-Link approach with suitably protected 3-oxo-D-gluco-furanose to introduce F/Cl as well as ester/amide functionalities at C-3 of glucose. In next steps, 5,6-O-isopropylidene group was converted to the 5-azido xylosugars that on opening of 1,2-acetonide group, and intramolecular Schmidt-Boyer reaction with TFA/H2O, in one pot, afforded lactams 3/4. Conformational aspect of δ-lactams was studied by the 1H NMR spectroscopy. The halogenated δ-lactams 3/4 showed no inhibition against different glycosidase enzymes.

Synthesis, conformational study, glycosidase inhibitory activity and molecular docking studies of dihydroxylated 4- and 5-amino-iminosugars.

An efficient methodology for the synthesis of new amino iminosugars 6a, 7a and 8, starting from D-glucose, is reported. The conformational study using (1)H NMR data showed that the amino iminosugar 6a exists in the (2)C5 while; the 7a and 8 exist in the (5)C2 conformation. The inhibition activities with different glycosidases showed that 6a and 7a are poor glycosidase inhibitors. However, amino iminosugar 8 showed selective inhibition against the ß-galactosidase (IC50 = 43 µM, Ki = 153 µM). These results are substantiated by the molecular docking studies.

Hypoglycemic and antihyperglycemic effect of Ceiba pentandra L. Gaertn in normal and streptozotocin-induced diabetic rats.

BACKGROUND: Ceiba pentandra (L.) Gaertn, commonly called silk-cotton tree, has been extensively used by traditional medicine practitioners in Northern and Eastern Nigeria in the control and management of diabetes. OBJECTIVE: To evaluate the hypoglycaemic and anti-hyperglycaemic effect of ethanolic extract of Ceiba pentandra bark in normal and streptozotocin induced diabetic rats. METHOD: Screening activity of the extract was carried out by OGTT. Diabetes mellitus was induced with streptozotocin and graded doses of the ethanolic bark extract (200 and 400 mg/kg, b.w.) were then administered to the experimentally diabetic rats. The blood glucose level was measured at different time intervals. RESULTS: The single dose study of C. pentandra extract at two different doses produced no significant hypoglycaemic effect in normal rats but C. pentandra (200 mg/kg) significantly decreased blood glucose level in diabetic rats. In OGTT, C. pentandra (200 mg/kg) significantly reduced elevated glucose level in normal and diabetic rats. In long term (21 days) study, C. pentandra (200 mg/kg) significantly decreased blood glucose level, total cholesterol and triglycerides level, prevented degeneration of liver and pancreas, and increased serum insulin level and liver glycogen content in diabetic rats. Acute toxicity study in rats did not show any signs of toxicity up to the dose of 2000 mg/kg b.w. CONCLUSION: The results reveal that the extract improved glucose tolerance in normal and streptozotocin-induced diabetic rats. Thus the study suggests that the C. pentandra bark extract could be beneficial in the management of type I diabetes.

Salacia reticulata improves serum lipid profiles and glycemic control in patients with prediabetes and mild to moderate hyperlipidemia: a double-blind, placebo-controlled, randomized trial.

The present randomized, double-blind, placebo-controlled study evaluated the efficacy and safety of Salacia reticulata leaves and root bark extracts in 29 patients with prediabetes and mild to moderate hyperlipidemia. Patients received either Salacia extracts (500 mg/day) or placebo along with therapeutic lifestyle changes for a period of 6 weeks. Efficacy was evaluated in terms of change in lipid profile and glycemic levels. The safety and tolerability was evaluated by a physical examination and clinical laboratory evaluations. Improvements in lipid profiles and glycemic levels were observed in Salacia extract-treated groups when compared to placebo at week 6. A statistical significant reduction was observed in low-density lipoprotein cholesterol and fasting blood sugar (FBS) levels at week 3 and 6 when treated with root bark extract. The leaves extract-treated group showed statistically significant reduction in FBS levels at week 6 only. No adverse events occurred and all safety parameters were within normal ranges during the study. This study revealed that treatment with S. reticulata was safe and well-tolerated and may be beneficial in the management of prediabetes and mild to moderate hyperlipidemia.

Polyhydroxylated homoazepanes and 1-deoxy-homonojirimycin analogues: Synthesis and glycosidase inhibition study.

The Johnson-Claisen rearrangement of D-gluco and L-ido-derived allylic orthoesters afforded gamma,delta-unsaturated ester that on ester reduction, epoxidation, regioselective oxirane opening by sodium azide and hydrogenation led to sugar amino alcohols--immediate precursors for 1-deoxy-homonojirimycin 3a,b, and polyhydroxylated homoazepanes 4a,b. Our synthetic approach and glycosidase inhibitory activity is reported.

Synthesis and evaluation of glycosidase inhibitory activity of N-butyl 1-deoxy-D-gluco-homonojirimycin and N-butyl 1-deoxy-L-ido-homonojirimycin.

Conjugate addition of n-butyl amine to d-glucose derived alpha,beta-unsaturated ester 4 afforded beta-amino esters 5a,b that on reduction of ester group, 1,2-acetonide deprotection, and reductive amination led to the formation of corresponding N-butyl 1-deoxy-D-gluco-homonojirimycin 2c and N-butyl 1-deoxy-L-ido-homonojirimycin 2d which were found to be selective beta-glucosidase inhibitors with an IC(50) value in millimolar range.