Novel benzofurane-pyrazole derivatives with anti-inflammatory, cyclooxygenase inhibitory and cytotoxicity evaluation

Novel benzofurane-pyrazolone hybrids have been synthesized for evaluating their anti-inflammatory and cytotoxic properties. 4-(2-chloroacetyl)-1,5-dimethyl-2-phenyl-1,2-dihydro-3H-pyrazol-3-one were reacted with α-hydroxy aldehyde or α-hydroxy ketone derivatives to obtain nine novel pyrazolone derivatives. Structures were successfully elucidated by 1H NMR, 13C NMR, IR and HRMS. Enzyme inhibitory activity was measured on cyclooxygenases (COXs) as considered to address anti-inflammatory activity. Compound 2 showed the highest activity on both COX-1 and COX-2 subtypes with 12.0 μM and 8.0 μM IC50, respectively. This activity was found close to indomethacin COX-2 inhibition measured as 7.4 μM IC50. Rest of the compounds (1, 3–9) showed 10.4–28.1 μM IC50 on COX-2 and 17.0–35.6 μM IC50 on COX-1 (Compound 1 has no activity on COX-1). Tested compounds (1–9) showed activity on NO production. Only compound was the 4, which showed a low inhibition on IL-6 levels. Cell viability was up to 60% at 100 μM for all compounds (1–9) on RAW 264.7 and NIH3T3 cell lines, thus compounds were reported to be noncytotoxic.

A method to construct the dynamic landscape of a bio-membrane with experiment and simulation

Biomolecular function is based on a complex hierarchy of molecular motions. While biophysical methods can reveal details of specific motions, a concept for the comprehensive description of molecular dynamics over a wide range of correlation times has been unattainable. Here, we report an approach to construct the dynamic landscape of biomolecules, which describes the aggregate influence of multiple motions acting on various timescales and on multiple positions in the molecule. To this end, we use 13C NMR relaxation and molecular dynamics simulation data for the characterization of fully hydrated palmitoyl-oleoyl-phosphatidylcholine bilayers. We combine dynamics detector methodology with a new frame analysis of motion that yields site-specific amplitudes of motion, separated both by type and timescale of motion. In this study, we show that this separation allows the detailed description of the dynamic landscape, which yields vast differences in motional amplitudes and correlation times depending on molecular position.

Immunosuppressive Isopimarane Diterpenes From Cultures of the Endophytic Fungus Ilyonectria robusta

Five new isopimarane diterpenes, robustaditerpene A-E (1–5), which include 19-nor-isopimarane skeleton and isopimarane skeleton, were isolated from the liquid fermentation of the endophytic fungus Ilyonectria robusta collected from Bletilla striata. The structure elucidation and relative configuration assignments of all compounds were accomplished by interpretation of NMR and HRESIMS spectrometric analyses and 13C NMR calculation. And the absolute configuration of 1-5 were identified by single-crystal X-ray diffraction and ECD calculation. Compound 3 inhibited lipopolysaccharide-induced B lymphocytes cell proliferation with an IC50 value at 17.42 ± 1.57 μM while compound 5 inhibited concanavalin A-induced T lymphocytes cell proliferation with an IC50 value at 75.22 ± 6.10 μM. These data suggested that compounds 3 and 5 may possess potential immunosuppressive prospect.

Structural Characterization, DFT Geometry Optimization, Cyclic Voltammetry and Biological Assay of (Tellurite-pyridine) Mixed Ligandcomplexesof Cd(II)

This research work presents spectral characterizations (IR, 1H NMR and 13C NMR) of anionic tellurito Cd(II) complexes that prepared using cyanopyridine derivatives as a polydentate ligands. Also, X-ray based techniques involving (EDX and XRD) are applied for cadmium complexes to realize elemental composition and average crystallographic coherence. Moreover, the electrochemical studies represented on cyclic voltammetry are determined for Cd)II) in (absence/presence) of ligands to detect the role of complexation in solution measurements. All the previous experimental investigations are supported with molecular modeling of the geometric optimized structures based on density function theory (DFT) for all compounds accompanied by the calculations of different energetic parameters such as EHOMO and ELUMO. Finally, anti-microbial (antibacterial and antifungal), anti-oxidant and Bleomycin dependent DNA damage are screened for all samples to predict the influence of metal complex formation on the biological activity of pyridyl ligands besides their priority.

Determination of chemical shifts in 6-condensed syringylic lignin model compounds

A small library of 6-substituted syringyl model compounds with aliphatic, carboxylic, phenylic, benzylic alcohols and brominated substituents were prepared. The influence of the substituents on the chemical shifts of the compounds was analyzed. All of model compounds showed a characteristic increase in the 13C NMR chemical shift of the methoxy group vicinal to the substitution. This 13C NMR peak and its corresponding correlation peak in HSQC could potentially be used to identify 6-condensation in syringylic lignin samples.

Efficient continuous flow-synthesis of novel spiro-naphthalene-1,2'-[1,3,4]oxadiazol-4-ones

The highly efficient cycloaddition reaction of hydrazonyl chlorides with 2,3-dichloro-1,4-naphthoquinone yielded pharmaceutically important spiro-naphthalene-1,2'-[1,3,4]oxadiazol-4-ones with moderate to good yields under batch and flow synthesis methods. The obtained products were elucidated by IR, 1H NMR, 13C NMR, HRMS and single crystal X-ray diffraction technique (only for 6h). The synthesized molecules have been subjected to theoretical analysis by quantum chemical calculations at B3LYP/6-31G(d,p) level, which provided supporting data for the experimental findings.

A Handy and Accessible Tool for Identification of Sn(II) in Toothpaste: Inclination to an Eco-Friendly Environment

An easily accessible colorimetric probe, a carbazole-naphthaldehyde conjugate (CNP), was successfully prepared for the selective and sensitive recognition of Sn(II) in different commercially-available toothpaste and mouth wash samples. The binding mechanism of CNP for Sn2+ was confirmed by UV-Vis, 1H and 13C NMR titrations. The proposed sensing mechanism was supported by quantum chemical calculations. Selective detection of Sn(II) in the nanomolar range (85 nM), among other interfering metal ions, makes it exclusive. Moreover, Sn2+ can be detected with a simple paper strip from toothpaste, which makes this method handy and easy accessible. The potential application of this system for monitoring Sn2+ can be used as an expedient tool in environmental and industrial purpose.

Triterpenoids From Kadsura coccinea With Their Anti-inflammatory and Inhibited Proliferation of Rheumatoid Arthritis-Fibroblastoid Synovial Cells Activities

One new 3,4-seco-17,13-friedo-lanostane triterpenoid heilaohuacid A (1), one new 3,4-seco-17,14-friedo-lanostane triterpenoid heilaohuacid B (2), five new 3,4-seco-lanostane triterpenoids heilaohuacids C-D (3–4) and heilaohumethylesters A-C (7–9), one new 3,4-seco-cycloartane triterpenoid heilaohuacid E (5), and one new intact-lanostane triterpenoid heilaohuacid F (6), together with twenty-two known analogues (10–31), were isolated from heilaohu. Their structures were determined using HR-ESI-MS data, 1D and 2D NMR spectra, 13C NMR calculations, and electronic circular dichroism (ECD) calculations. Heilaohuacids A and B (1 and 2) contain a 3,4-seco ring A and unprecedented migration of Me-18 from C-13 to C-17 or C-14 to C-18. This type of lanostane triterpenoid derivatives was rarely reported so far. More importantly, all compounds against inflammatory cytokines IL-6 and TNF-α levels on LPS-induced RAW 264.7 macrophages were evaluated, and compounds 4 and 31 significantly inhibited the release level of IL-6 with IC50 values of 8.15 and 9.86 μM, respectively. Meanwhile, compounds 17, 18, and 31 significantly inhibited proliferation of rheumatoid arthritis-fibroblastoid synovial (RA-FLS) cells in vitro with IC50 values of 7.52, 8.85, and 7.97 μM, respectively.

Synthesis, Characterization and Photophysicochemical Properties of Zinc(Ii) Phthalocyanine With New Benzenesulfonamide Derivative Substituents

Novel (E)-4-((5-bromo-2-hydroxy-3-methoxybenzylidene)amino)-N-(pyridin-2-yl)benzenesulfonamide 1, (E)-4-((5-bromo-2-(3,4-dicyanophenoxy)-3-methoxybenzylidene)amino)-N-(pyridin-2-yl)benzene sulfonamide 2 and 2(3),9(10),16(17),23(24)-tetra-[(E)-4-((5-bromo-3-methoxy-2-(λ1-oxidanyl)benzyl idene)amino)-N-(pyridine-2-yl)benzenesulfonamide]phthalocyaninato zinc(II) phthalocyanine 3 were synthesized. Their (1-3) structures were illuminated with spectroscopic methods such as FT-IR, 1H NMR,13C NMR, UV–vis, MALDI-TOF mass spectra and also elemental analysis. The spectroscopic, photophysical and photochemical properties of the zinc(II) phthalocyanine 3 were investigated in dimethyl sulfoxide and its effects on the above mentioned properties were reported as a result of containing new type benzenesulfonamide derivatives as substituents. In addition, its above-mentioned properties were reported by comparing different species with those of their substituted and/or unsubstituted counterparts. The zinc(II) phthalocyanine 3 has photosensitizing abilities suitable and sufficient especially for photocatalytic applications.

Design, synthesis, and biological evaluation of novel urolithins derivatives as potential phosphodiesterase II inhibitors

A series of urolithins derivatives were designed and synthesized, and their structures have been confirmed by 1H NMR, 13C NMR, and HR-MS. The inhibitory activity of these derivatives on phosphodiesterase II (PDE2) was thoroughly studied with 3-hydroxy-8-methyl-6H-benzo[C]chromen-6-one and 3-hydroxy-7,8,9,10-tetrahydro-6H-benzo[C] chromen-6-one as the lead compounds. The biological activity test showed that compound 2e had the best inhibitory activity on PDE2 with an IC50 of 33.95 μM. This study provides a foundation for further structural modification and transformation of urolithins to obtain PDE2 inhibitor small molecules with better inhibitory activity.