173 publications from this institution
Novel azo-bis-ebselen compounds 7 were prepared by reduction of 7-nitro-2-aryl-1,2-benzisoselenazol-3(2H)-ones 3 and 6 with sodium benzenetellurolate, NaTeC6H5, and by reaction of 2-bromo-3-nitrobenzamides with Na2Se2. The X-ray structure of 7b showed that the molecule, due to strong intramolecular secondary Se···N interactions, is completely planar. Azo-compounds 7 upon further reaction with NaTeC6H5 were reductively cleaved to provide 2 equiv of the corresponding aromatic amine. The weak Se-N bond was not stable enough to survive the reaction conditions, and diselenides 8 were isolated after workup. Whereas azo-bis-ebselens 7 were poor mimics of the glutathione peroxidase (GPx)-enzymes, nitroebselens 3, 6, and 11b and diselenides 8 were 3-6-fold more active than ebselen. Based on 77Se NMR spectroscopy, a catalytic cycle for diselenide 8b, involving aminoebselen 14, was proposed. As assessed by chemiluminescence measurements, the good GPx-mimics could reduce production of reactive oxygen species (ROS) in stimulated human mononuclear cells more efficiently than Trolox. No toxic effects of the compounds were seen in MC3T3-cells at 25 μM.
No abstract is provided for this article.
An unexpected intramolecular coupling of imines (I) and (III) under conditions A) produces the title compounds as major or sole products.
One of the vitamin B6 vitamers, pyridoxine, was modified to incorporate selenium in various oxidation states in place of the methyl group in position 2. Such compounds were conveniently accessed by treatment of bis‐4,5‐(carboethoxy)‐2‐iodo‐3‐pyridinol with disodium diselenide and LiAlH 4 ‐reduction. After work‐up, selone 7 was isolated in good yield as an air‐stable crystalline material. Hydrogen bonding to the neighboring hydroxyl group, as revealed by the short intramolecular Se ⋅⋅⋅ H distance in the crystal structure is likely to provide extra stabilization to the compound. Computational studies showed that selone 7 is more stable than the corresponding selenol tautomer by 12.2 kcal mol −1 . Hydrogen peroxide oxidation of the selone 7 afforded diselenide 12 , and, on further oxidation, seleninic acid 13 . Treatment of the seleninic acid with thiophenol provided an isolable selenosulfide 14 . The glutathione peroxidase‐like properties of the pyridoxine‐derived compounds were assessed by using the coupled reductase method. Seleninic acid 13 was found to be twofold more active than ebselen. The chain‐breaking capacity of the pyridoxine compounds were studied in a water/chlorobenzene membrane model containing linoleic acid as an oxidizable substrate and N ‐acetylcysteine as a thiol reducing agent. Diselenide 15 could match α‐tocopherol when it comes to reactivity towards peroxyl radicals and inhibition time.
Singlet fission (SF) is a process of multi-exciton generation in molecular aggregates where two independent triplet states are formed <i>via</i> an intermediate correlated triplet-triplet <sup>1</sup>(TT) pair state. SF has been shown to occur within a minimal dimeric unit with chromophores having monomer triplet energies that are half the allowed bright singlet state energy. However, optimal singlet fission rates can only be derived if structural rules are formulated for tunable interchromophoric coupling between the two monomer units, which has remained a significant challenge in the community. In order to uncover the electronic nature of the dynamic <sup>1</sup>(TT) stabilization in generic supramolecular dimeric constructs, herein we have synthesized five new napthalene-diimde (NDI) cyclophanes by altering the distance and angle between the NDI units. Using a combination of transient absorption spectroscopy supported by high-level electronic structure calculations, we find that SF is tolerant in these rigid dimeric structures up to distances of 4.5 Å while the rise of the <sup>1</sup>(TT)-state gradually slows down from 400 fs to 4.6 ps concomitant with the decrease in the inter-chromophoric electronic coupling. Our work therefore demonstrates that the thermodynamic criterion of singlet exciton fission isn't in the singlet-triplet energetics of the constitutive monomer but rather in the stabilization of the multiexcitonic <sup>1</sup>(TT) pair state in its minimal dimeric unit.
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.
Experimental studies have indicated the importance of cAMP and cGMP in modulation of peripheral sensory neurons leading to hyperalgesic response. The conce
Persistent stimulation of nociceptors and C-fibers by tissue injury causes hyperalgesia and allodynia by sensitization of nociceptors and facilitation of s
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.
No abstract is provided for this article.
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.
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.
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.
Although the phenomenon of opioid tolerance and dependence has been widely investigated, neither opioid nor non-opioid mechanisms are completely understood. In view of the modulation of 5-HT transport into presynaptic terminals in the brain by nitric oxide (NO) via cGMP, and the existence of a tonic 5-HTergic inhibition of dopamine release, the present study investigated the effect of fluoxetine, a selective serotonin reuptake inhibitor, and NO modulators L-N(G)-nitroarginine methyl ester (L-NAME; NO synthase inhibitor) and L-Arginine (substrate for nitric oxide synthase) alone or in combination against morphine tolerance and dependence. Animals developed tolerance to the antinociceptive effect of morphine (10 mg/kg s.c. twice daily) on day 3 and the degree of tolerance was further enhanced on days 9 and 10. The development of tolerance to the antinociceptive effect of morphine was delayed by prior administration of fluoxetine (10 mg/kg i.p, twice daily for 9 days) and L-NAME (10 mg/kg i.p. twice daily for 9 days) alone or in combination. It was accentuated by L-Arginine (50 mg/kg i.p. twice daily for 9 days) alone or in combination with fluoxetine (10 mg/kg i.p. twice daily for 9 days). Similarly, fluoxetine (10 mg/kg i.p.) or L-NAME (10 mg/kg i.p.), when administered acutely on day 10, reversed morphine-induced tolerance. L-Arginine (50 mg/kg i.p.) however, when administered acutely on day 10, accentuated morphine tolerance. Fluoxetine (10 mg/kg i.p. twice daily for 9 days) suppressed the development of morphine dependence as assessed by naloxone (2 mg/kg i.p.)-precipitated withdrawal jumps. This suppression of dependence was potentiated by L-NAME (10 mg/kg i.p. twice daily for 9 days) and reversed by L-Arginine (50 mg/kg i.p. twice daily for 9 days), respectively. Acute administration of the respective drugs on day 10 modulated morphine dependence in a similar fashion. L-Arginine also reversed fluoxetine-induced weight loss in morphine-dependent animals. The present study demonstrated that fluoxetine suppressed the dependence and development of tolerance to the antinociceptive effect of morphine. Fluoxetine-induced suppression was potentiated by L-NAME and accentuated by L-Arginine. The results therefore suggest that a complex phenomenon such as morphine tolerance and dependence might involve close interplay of the NO-c GMP/5-HT/DA receptor system. To the best of the authors' knowledge, this is the first report to suggest targeting this cascade for amelioration of opioid tolerance and withdrawal syndrome.
