Synthesis and Investigations of Building Blocks with Dibenzo[b,f] Oxepine for Use in Photopharmacology

The synthesis of photoswitchable azo-dibenzo[b,f]oxepine derivatives and microtubule inhibitors were described. Subsequently, we examined the reaction of methoxy derivative 3-nitrodibenzo[b,f]oxepine with different aldehydes and in the presence of BF3·OEt2 as a catalyst. Our study provided a very concise method for the construction of the azo-dibenzo[b,f]oxepine skeleton. The analysis of products was run using experimental and theoretical methods. Next, we evaluated the E/Z isomerization of azo-dibenzo[b,f]oxepine derivatives, which could be photochemically controlled using visible-wavelength light.

Gut Microbiota Induced by Pterostilbene and Resveratrol in High-Fat-High-Fructose Fed Rats: Putative Role in Steatohepatitis Onset

Resveratrol and its 2-methoxy derivative pterostilbene are two phenolic compounds that occur in foodstuffs and feature hepato-protective effects. This study is devoted to analysing and comparing the metabolic effects of pterostilbene and resveratrol on gut microbiota composition in rats displaying NAFLD induced by a diet rich in saturated fat and fructose. The associations among changes induced by both phenolic compounds in liver status and those induced in gut microbiota composition were also analysed. For this purpose, fifty Wistar rats were distributed in five experimental groups: a group of animals fed a standard diet (CC group) and four additional groups fed a high-fat high-fructose diet alone (HFHF group) or supplemented with 15 or 30 mg/kg bw/d of pterostilbene (PT15 and PT30 groups, respectively) or 30 mg/kg bw/d of resveratrol (RSV30 group). The dramatic changes induced by high-fat high-fructose feeding in the gut microbiota were poorly ameliorated by pterostilbene or resveratrol. These results suggest that the specific changes in microbiota composition induced by pterostilbene (increased abundances of Akkermansia and Erysipelatoclostridium, and lowered abundance of Clostridum sensu stricto 1) may not entirely explain the putative preventive effects on steatohepatitis.

Structural investigation of N-[2-(4-fluoro-3-phenoxybenzoyl)hydrazinecarbothioyl]benzamide and N-[2-(4-fluoro-3-phenoxybenzoyl)hydrazinecarbothioyl]-4-methoxybenzamide

The compound N-[2-(4-fluoro-3-phenoxybenzoyl)hydrazinecarbothioyl]benzamide, C21H16FN3O3S, crystallizes in the monoclinic centrosymmetric space group P21/c and its molecular conformation is stabilized via an intramolecular N—H...O hydrogen bond. The corresponding para-methoxy derivative, namely, N-[2-(4-fluoro-3-phenoxybenzoyl)hydrazinecarbothioyl]-4-methoxybenzamide, C22H18FN3O4S, crystallizes in the monoclinic centrosymmetric space group C2/c. The supramolecular network mainly comprises N—H...O, N—H...S and C—H...O hydrogen bonds, which contribute towards the formation of the crystal structures for the two molecules. The different intermolecular interactions have been further analysed using Hirshfeld surface analysis and fingerprint plots.

Hyaluronidase and degranulation inhibitors from the edible roots of Oenanthe javanica including seric acids F and G that were obtained by heating

ABSTRACT Oenanthe javanica is a vegetable grown in East Asia and Australia in which the roots and aerial parts are boiled together to make certain traditional dishes. Nineteen compounds (1-19) were isolated from O. javanica roots and the chemical structures of 2 new norlignans were determined. The inhibitory effects of the compounds on hyaluronidase and degranulation in RBL-2H3 cells were evaluated to determine antiallergic and antiinflammation activities. Saponins (2-4) and the new norlignan seric acid G (12) were among the active compounds identified. Seric acid G (12), a methoxy derivative of seric acid F (11), was obtained as an interconverting mixture of 3:1 trans-cis isomers. Seric acids F and G (11, 12) were derived from seric acids C (10) and E, respectively, by decarboxylation and dehydration reactions that occurred during heating. It was confirmed by HPLC analysis that all eleven of the O. javanica cultivars contained seric acid C (10).

Molecular and Biochemical Basis of Fluoroquinolones-Induced Phototoxicity—The Study of Antioxidant System in Human Melanocytes Exposed to UV-A Radiation

Phototoxicity of fluoroquinolones is connected with oxidative stress induction. Lomefloxacin (8-halogenated derivative) is considered the most phototoxic fluoroquinolone and moxifloxacin (8-methoxy derivative) the least. Melanin pigment may protect cells from oxidative damage. On the other hand, fluoroquinolone–melanin binding may lead to accumulation of drugs and increase their toxicity to skin. The study aimed to examine the antioxidant defense system status in normal melanocytes treated with lomefloxacin and moxifloxacin and exposed to UV-A radiation. The obtained results demonstrated that UV-A radiation enhanced only the lomefloxacin-induced cytotoxic effect in tested cells. It was found that fluoroquinolones alone and with UV-A radiation decreased superoxide dismutase (SOD) activity and SOD1 expression. UV-A radiation enhanced the impact of moxifloxacin on hydrogen peroxide-scavenging enzymes. In turn, lomefloxacin alone increased the activity and the expression of catalase (CAT) and glutathione peroxidase (GPx), whereas UV-A radiation significantly modified the effects of drugs on these enzymes. Taken together, both analyzed fluoroquinolones induced oxidative stress in melanocytes, however, the molecular and biochemical studies indicated the miscellaneous mechanisms for the tested drugs. The variability in phototoxic potential between lomefloxacin and moxifloxacin may result from different effects on the antioxidant enzymes.

Control of the Photo-Isomerization Mechanism in 3H-Naphthopyrans to Prevent Formation of Unwanted Long-Lived Photoproducts

In the photochromic reactions of 3H-naphthopyrans, two colored isomers TC (transoid-cis) and TT (transoid-trans) are formed. In terms of optimized photo-switchable materials, synthetic efforts are nowadays evolving toward developing 3H-naphthopyran derivatives that would not be able to photoproduce the long-living transoid-trans, TT, photoproduct. The substitution with a methoxy group at position 10 results in significant reduction of the TT isomer formation yield. The TC photophysics responsible for TT suppression were revealed here using a combination of multi-scale time resolved absorption UV-vis spectroscopy and ab initio calculations. The substitution changes the TC excited-state potential energy landscape, the bicycle-pedal isomerization path is favored over the rotation around a single double bond. The bicycle-pedal path is aborted in halfway to TT formation due to S1→S0 internal conversion populating back the TC species in the ground electronic state. This is validated by a shorter TC S1 state lifetime for methoxy derivative in comparison to that of the parent-unsubstituted compound (0.47 ± 0.05 ps vs. 0.87 ± 0.09 ps) in cyclohexane.

Antispasmodic Activity of Prenylated Phenolic Compounds from the Root Bark of Morus nigra

Black mulberry is a widely acknowledged ancient traditional medicine. Its extract and constituents have been reported to exert various bioactivities including antimicrobial, hypotensive, analgesic etc. effects. While black mulberry preparations are also used as antispasmodic agents in folk medicine, no related studies are available on its isolated constituents. Through an extensive chromatographic purification, seven phenolic compounds were isolated from the methanol extract of Morus nigra root bark, including morusin (1), kuwanon U (2), kuwanon E (3), moracin P (4), moracin O (5), albanol A (6), and albanol B (7). A complete NMR signal assignment of moracin P and O was achieved, and related literature errors confusing the identity of moracin derivatives are hereby clarified. Compounds 2, 5 and 7 were identified as strong antispasmodic agents on isolated rat ileum and tracheal smooth muscles, while compound 3, a methoxy derivative of 2, was inactive. Moracin O (5) inhibited the ileal and tracheal smooth muscle contractions with Emax values of 85% and 302 mg, respectively. Those actions were superior as compared with papaverine. Our findings demonstrate that prenylated arylbenzofurans, geranylated flavonoids and Diels-Alder adducts from Morus nigra are valuable antispasmodic agents. Compounds 2, 5 and 7 are suggested as marker compounds for quality control of antispasmodic mulberry preparations. Moracin O (5) is a new lead compound for related drug development initiatives.

Dimethyloxonium and Methoxy Derivatives of nido-Carborane and Metal Complexes Thereof

9-Dimethyloxonium, 10-dimethyloxonium, 9-methoxy and 10-methoxy derivatives of nido-carborane (9-Me2O-7,8-C2B9H11, 10-Me2O-7,8-C2B9H11, [9-MeO-7,8-C2B9H11]−, and [10-MeO-7,8-C2B9H11]−, respectively) were prepared by the reaction of the parent nido-carborane [7,8-C2B9H12]− with mercury(II) chloride in a mixture of benzene and dimethoxymethane. Reactions of the 9 and 10-dimethyloxonium derivatives with triethylamine, pyridine, and 3-methyl-6-nitro-1H-indazole result in their N-methylation with the formation of the corresponding salts with 9 and 10-methoxy-nido-carborane anions. The reaction of the symmetrical methoxy derivative [10-MeO-7,8-C2B9H11]− with anhydrous FeCl2 in tetrahydrofuran in the presence of t-BuOK results in the corresponding paramagnetic iron bis(dicarbollide) complex [8,8′-(MeO)2-3,3′-Fe(1,2-C2B9H10)2]−, whereas the similar reactions of the asymmetrical methoxy derivative [9-MeO-7,8-C2B9H11]− with FeCl2 and CoCl2 presumably produce the 4,7′-isomers [4,7′-(MeO)2-3,3′-M(1,2-C2B9H10)2]− (M = Fe, Co) rather than a mixture of rac-4,7′- and meso-4,4′-isomers.

Structural, energetic and spectroscopic studies of new luminescent complexes based on 2-(2′-hydroxyphenyl)imidazo[1,2-a]pyridines and 1,2-phenylenediboronic acid

Three new blue-luminescent complexes of selected imidazo[1,2-a]pyridine derivatives and 1,2-phenylenediboronic acid have been synthesized and structurally characterized using single-crystal X-ray diffraction. Additionally, the crystal structures of two of the (N,O)-donor compounds have been evaluated for the first time. The crystal packing and molecular motifs observed in the studied crystals have been thoroughly analysed, including computational studies, and are also discussed within the context of analogous systems reported in the literature. It appears that the new compounds form different crystal networks with regard to the asymmetric unit content and packing, although some similarities can be found. In all cases a typical centrosymmetric dimer bound via boronic acid groups is formed, characterized by an interaction energy of about −80 kJ mol−1, while the 2-(2′-hydroxyphenyl)imidazo[1,2-a]pyridine complex and its methoxy derivative form solvate structures, somewhat resembling the previously studied 8-oxyquinolinate analogues. As far as the spectroscopic properties are concerned, the lowest energy excitation observed in the studied complexes is based on the highest occupied molecular orbital–lowest unoccupied molecular orbital transition, and both these molecular orbitals are centred predominantly on the (N,O)-donor species according to the results of time-dependent density functional theory. Thus, the charge transfer observed for the 8-oxyquinolinate equivalents does not occur in these cases. Consequently, the spectroscopic behaviour of the series is very much comparable with that of the parent imidazo[1,2-a]pyridine derivatives, if the excited-state intramolecular proton-transfer process does not take place, as shown by the absorption and emission spectra collected in toluene and acetone solutions. Complexation causes a reduction in the Stokes shift compared with the respective (N,O)-donor molecules.

2-Iodo-N-isopropyl-5-methoxybenzamide as a highly reactive and environmentally benign catalyst for alcohol oxidation

Several N-isopropyliodobenzamides were evaluated as catalysts for the oxidation of benzhydrol to benzophenone in the presence of Oxone® (2KHSO5·KHSO4·K2SO4) as a co-oxidant at room temperature. A study on the substituent effect of the benzene ring of N-isopropyl-2-iodobenzamide on the oxidation revealed that its reactivity increased in the following order of substitution: 5-NO2 < 5-CO2Me, 3-OMe < 5-OAc < 5-Cl < H, 4-OMe < 5-Me < 5-OMe. The oxidation of various benzylic and aliphatic alcohols using a catalytic amount of the most reactive 5-methoxy derivative successfully resulted in moderate to excellent yields of the corresponding carbonyl compounds. The high reactivity of the 5-methoxy derivative at room temperature is a result of the rapid generation of the pentavalent species from the trivalent species during the reaction. 5-Methoxy-2-iodobenzamide would be an efficient and environmentally benign catalyst for the oxidation of alcohols, especially benzylic alcohols.