Publications

CCDC 874501: Experimental Crystal Structure Determination

An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.

CCDC 808890: Experimental Crystal Structure Determination

Effect of a Bromo Substituent on the Glutathione Peroxidase Activity of a Pyridoxine-like Diselenide

In search for better mimics of the glutathione peroxidase enzymes, pyridoxine-like diselenides 6 and 11, carrying a 6-bromo substituent, were prepared. Reaction of 2,6-dibromo-3-pyridinol 5 with sodium diselenide provided 6 via aromatic nucleophilic substitution of the 2-bromo substituent. LiAlH4 caused reduction of all four ester groups and returned 11 after acidic workup. The X-ray structure of 6 showed that the dipyridyl diselenide moiety was kept in an almost planar, transoid conformation. According to NBO-analysis, this was due to weak intramolecular Se···O (1.1 kcal/mol) and Se···N-interactions (2.5 kcal/mol). That the 6-bromo substituent increased the positive charge on selenium was confirmed by NPA-analysis and seen in calculated and observed 77Se NMR-shifts. Diselenide 6 showed a more than 3-fold higher reactivity than the corresponding des-bromo compound 3a and ebselen when evaluated in the coupled reductase assay. Experiments followed for longer time (2 h) confirmed that diselenide 6 is a better GPx-catalyst than 11. On the basis of 77Se-NMR experiments, a catalytic mechanism for diselenide 6 was proposed involving selenol, selenosulfide and seleninic acid intermediates. At low concentration (10 μM) where it showed only minimal toxicity, it could scavenge ROS produced by MNC- and PMNC-cells more efficiently than Trolox.

Generation and Sonication of α-synuclein Fibrils v1

Animal models that accurately recapitulate the accumulation of alpha-synuclein (α-syn) inclusions, progressive neurodegeneration of the nigrostriatal system and motor deficits can be useful tools for Parkinson's disease (PD) research. The preformed fibril (PFF) synucleinopathy model in rodents generally displays these PD-relevant features, however, the magnitude and predictability of these events is far from established. We therefore have optimized the synthesis generation of α-syn fibrils to ensure reliable, robust results. These fibrils can be added to neurons in culture, differentiated iPSCs, or injected into mice or rats. The protocol includes steps for fibril synthesis as well as sonication for fibril fragmentaion which is a critical step for inducing formation of α-syn inclusions.

Synthesis, Characterization and Computational studies of Some New Vanillin Derivatives for Cosmetic Purpose

Prolonged exposure to sun radiation may lead to early onset of skin aging and development of skin cancer. Skin possesses inherent antioxidant protection, but, when these defenses are not properly balanced, reactive oxygen species have the potential to harm cellular structures. Therefore, it is essential to produce novel vanillin derivatives as promising lead candidates in the field of pharmaceutical research. This study aimed to synthesize vanillin derivatives, preparation of nanoemulsions and evaluate their Sun protection factor (SPF) response. Vanillin derivatives (V-1 to V-5) were synthesized by condensing 4-(benzyloxy)-3-methoxybenzaldehyde (I) with substituted anilines in ethanol, using glacial acetic acid as a catalyst. The key intermediate, 4-(benzyloxy)-3-methoxybenzaldehyde (I), was obtained through the reaction of vanillin with benzyl bromide in the presence of anhydrous potassium carbonate in dimethylformamide (DMF). The structures of the newly synthesized derivatives were characterized using IR, ¹H NMR and ¹³C NMR spectroscopy. Various physicochemical and pharmacokinetic properties of the synthesized derivatives were computed to evaluate their potential as drug candidates. All synthesized compounds were docked with MMP1 and MMP2. Subsequently, nanoemulsion formulations NEV-1 to NEV-5 were prepared and characterized, followed by in vitro and in vivo SPF evaluations. All the compounds satisfied the Lipinski's rule and might be candidates for biological study. All the-synthesized derivatives showed toxicity class classification 4. Toxicological prediction results showed that all the synthesized compounds were predicted to be nonhepatotoxic, nonmutagenic and noncytotoxic. The synthesized compounds V-5, V-4 and V-3 shown the strongest binding affinity with Matrix metalloproteinase-1 (MMP1) but V-3 and V-4 showed the strong binding affinities with Matrix metalloproteinase-2 (MMP2). Nanoemulsion prepared successfully and the maximum particle size 902 was obtained for NEV-2 but minimum 66.30 obtained for NEV-4. NEV-5 showed the highest PDI value 0.511. NEV-2 showed the highest zeta potential value 5.92. In vitro SPF study, it was found that NEV-4 and NEV-3 showed the highest SPF values 8.641 and 6.876 respectively. The in vivo SPF determination was done and it was found that NEV-4 and NEV-3 showed the highest SPF values 8.73 and 6.860 respectively. Based upon present findings, it was concluded that synthesized derivatives are new and significantly potent to have beneficial impact on skin to protect from sunburn and same may be used for cosmetic purpose.

Response to Puvanendran et al.

No abstract is provided for this article.

Kinetics & Mechanism of Alkaline Ferricyanide Oxidation of 2-Methylpentane-2,4-diol & Pentane-1,5-diol

CCDC 1538259: Experimental Crystal Structure Determination

An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.

Sildenafil induces hyperalgesia via activation of the NO-cGMP pathway in the rat neuropathic pain model

Persistent stimulation of nociceptors and C-fibers by tissue injury causes hyperalgesia and allodynia by sensitization of nociceptors and facilitation of s

Exploring Arsenic Transformation and Chemotaxis in a Pseudomonas sp.

An arsenic-resistant bacteria (strain PKA 200) was isolated from the Hindon River (Ghaziabad) after analyzing its water sample. Strain PKA 200 belongs to the Pseudomonas genus and can convert harmful arsenite [As (III)] into less harmful arsenate [As(V)]. Strain PKA 200 exhibits a remarkable ability to sense and move towards arsenite. Strain PKA 200 is a promising candidate for studying how bacteria sense and transform arsenic. Here, we report a novel circular plate assay to demonstrate both chemotaxis and biotransformation of arsenite by Pseudomonas sp. PKA 200.

Regenerable Thiophenolic Radical-Trapping Antioxidants

Diphenyl disulfides carrying alkyltelluro groups in the o-, m-, and p-positions were prepared using ortho-lithiation and lithium halogen exchange reactions. The novel antioxidants showed only minimal inhibitory effect on the azo-initiated peroxidation of linoleic acid in chlorobenzene until reduced to the corresponding thiophenols by tris(2-carboxyethyl)phosphine (TCEP). The best in situ generated thiophenol (from 7c) under these conditions quenched peroxyl radicals more efficiently than α-tocopherol with an almost 3-fold increase in inhibition time.

Anti‐inflammatory effect of licofelone against various inflammatory challenges

We investigated the pharmacological profile of licofelone [6‐(4‐chlorophenyl)‐2,3‐dihydro‐2,2‐dimethyl‐7‐phenyl‐1H‐pyrrolizine‐5‐acetic acid] against different inflammogens. The anti‐inflammatory and anti‐hyperalgesic effect of licofelone (2, 30 and 100 mg/kg, p.o.) against all the challenges was statistically significant ( P < 0.05) when compared with control and indomethacin (10 mg/kg, p.o.). The ED 50 value of 19.1 mg/kg (onset by 2 h, duration: short), 13.0 mg/kg and 16.8 mg/kg (onset by 1 h, duration: long) was observed for licofelone against carrageenan‐, arachidonic acid‐ and bradykinin‐induced paw oedema, respectively. Similarly, licofelone showed ED 50 value of 47.6 mg/kg (onset by 1 h, duration: long), 92.2 mg/kg (onset by 1 h, duration: medium), and 78.6 mg/kg (onset by 2 h, duration: medium) against carrageenan‐, arachidonic acid‐ and bradykinin‐induced mechanical hyperalgesia, respectively. The rank order of potency based on percent inhibition and percent reversal against inflammation and mechanical hyperalgesia, respectively, was found to be licofelone > indomethacin. Moreover, licofelone (10–100 mg/kg, p.o.) significantly ( P < 0.05) and dose‐dependently prevented the Freund's adjuvant‐induced increased vascularity in mice (vascularity index; 10 mg/kg: 0.059 ± 0.015; 20 mg/kg: 0.048 ± 0.004; 30 mg/kg: 0.039 ± 0.012; 100 mg/kg: 0.025 ± 0.015 vs. control: 0.0285 ± 0.003). Furthermore, the results suggested that dual inhibitors of cyclooxygenase and lipoxygenase like licofelone provide an effective control of inflammation and hyperalgesia against acute inflammation/hyperalgesia in rats and mice.

Predicting compound dry-hot events over global land areas based on large-scale climate indices

On the antinociceptive effect of fluoxetine, a selective serotonin reuptake inhibitor

Antidepressant drugs are reported to be used as co-analgesics in clinical management of migraine and neuropathic pain. The mechanism through which they alleviate pain remains unknown. The present study explores the possible mechanism of a selective serotonin reuptake inhibitor (SSRI) fluoxetine-induced antinociception in animals. Acetic acid-induced writhing, hot plate and tail-flick test were used to assess fluoxetine-induced antinociception. Fluoxetine (5–20 mg kg−1, i.p.) produced a significant and dose-dependent antinociceptive effect against acetic acid-induced writhing in mice. Fluoxetine (20 mg kg−1) also exhibited antinociceptive effect in tail flick as well as hot plate assays. Further, i.c.v. administration of fluoxetine showed significant antinociception against writhing test in rats. However, fluoxetine (1 μg/10 μl/rat, i.c.v.) did not exhibit any antinociceptive effect in serotonin-depleted animals. Further, pindolol (10 mg kg−1, i.p.) enhanced fluoxetine-induced antinociceptive effect. The antinociceptive effect of fluoxetine was sensitive to blockade by naloxone (5 mg kg−1, i.p.) and naltrexone (5 mg kg−1, i.p.). These data suggest that fluoxetine-induced antinociception involves both central opioid and the serotoninergic pathways.

Positioning dual inhibitors in the treatment of pain and inflammatory disorders

CCDC 734614: Experimental Crystal Structure Determination

An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.

CCDC 996308: Experimental Crystal Structure Determination

An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.

ChemInform Abstract: Intramolecular C-C Coupling of 2,6-Disubstituted-1-bromoaryls for Dihydrophenanthridines.

An unexpected intramolecular coupling of imines (I) and (III) under conditions A) produces the title compounds as major or sole products.

CCDC 1427923: Experimental Crystal Structure Determination

An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.