Organic Selenium Compounds,Part IV: Synthesis and Applications of Some New Diaryl Selenides Containing Azomethine and Oxazole Moieties

3,3′-Diacetyloxy (2), 3,3′-dihydroxy (3), 4,4′-diamino (4), and 4-amino (5) diphenylselenide derivatives were prepared as new precursors for the title studies. Compound 6 was obtained by condensation of 4 with an appropriate aromatic aldehyde. Unsymmetrical diphenylselenides 7 and 8 were obtained by condensation of 4 and/or 5 with an aromatic aldehyde. Compound 7 undergoes facile condensation with the same aldehyde present in its arylidene moiety to yield 6, while condensation with another different aromatic aldehyde yielded unsymmetrical 4-arylideneamino diphenylselenide derivative 9. Oxidation of 6, 8, and 9 using lead tetra acetate and/or N-bromosuccinimide yielded symmetrical bis-(2-aryl benzoxazol-6-yl) (10), unsymmetrical 3′-hydroxy, 2-aryl benzoxazol-6-yl selenides (11), and 2-aryl benzoxazol-6-yl, 2′-aryl′ benzoxazol-6′-yl selenide derivatives (12), respectively. Compound 10 was prepared in one-pot unequivocal synthesis by fusion of 4 with the appropriate aromatic aldehyde, while 12 was prepared by fusion of 4 with two different aromatic aldehydes. In certain cases, 6 and 9 were heated on a direct flame until complete homogeneity afforded the corresponding 10 and 12. The structures of the synthesized compounds are based on physical data, IR, ¹H NMR, ¹³C NMR, chemical means, and mass spectral data. Some of the synthesized compounds were biologically tested.

Supplemental materials are available for this article. Go to the publisher's online edition of Phosphorus, Sulfur, and Silicon and the Related Elements to view the free supplemental file.     

Electron- and energy-transfer properties of hydrophilic carotenoids

The antioxidant activities-expressed as the electron-donating properties-of five hydrophilic carotenoids (carotenoid surfactants) and three related hydrophobic carotenoids were investigated by flash photolysis. The electron-transfer rates of the carotenoids to the triplet state of the sensitizer 2-nitronaphthalene and the energy transfer rates of triplet 2-nitronaphthalene to the carotenoids were determined. The results demonstrate that the electron-donating effects of the hydrophilic and hydrophobic carotenoids were comparable when evaluated in acetonitrile. In the presence of water, however, electron transfer (i.e., antioxidant efficiency) was enhanced by a factor of four for the hydrophilic carotenoids. The increased hydrophilicity of carotenoids, therefore, could expand their antioxidant properties, thus facilitating their use as aqueous-phase radical scavengers. At the same time, it was shown that supramolecular assembly ("aggregation") of the amphiphilic carotenoids prevented electron transfer, thus deactivating the antioxidant function. Modulation of the biophysical properties of carotenoids through synthetic modification is capable of increasing the biological and medical utility of this natural class of predominantly hydrophobic antioxidant compound.     

The Anti-Inflammatory Effect of a γ-Lactone Isolated from Ostrich Oil of Struthio camelus (Ratite) and Its Formulated Nano-Emulsion in Formalin-Induced Paw Edema

The ostrich oil of Struthio camelus (Ratite) found uses in folk medicine as an anti-inflammatory in eczema and contact dermatitis. The anti-inflammatory effect of a γ-lactone (5-hexyl-3H-furan-2-one) isolated from ostrich oil and its formulated nano-emulsion in formalin-induced paw edema was investigated in this study. Ostrich oil was saponified using a standard procedure; the aqueous residue was fractionated, purified, and characterized as γ-lactone (5-hexyl-3H-furan-2-one) through the interpretation of IR, NMR, and MS analyses. The γ-lactone was formulated as nano-emulsion using methylcellulose (MC) for oral solubilized form. The γ-lactone methylcellulose nanoparticles (γ-lactone-MC-NPs) were characterized for their size, shape, and encapsulation efficiency with a uniform size of 300 nm and 59.9% drug content. The γ-lactone was applied topically, while the formulated nanoparticles (NPs) were administered orally to rats. A non-steroidal anti-inflammatory drug (diclofenac gel) was used as a reference drug for topical use and ibuprofen suspension for oral administration. Edema was measured using the plethysmograph method. Both γ-lactone and γ-lactone-MC-NPs showed reduction of formalin-induced paw edema in rats and proved to be better than the reference drugs; diclofenac gel and ibuprofen emulsion. Histological examination of the skin tissue revealed increased skin thickness with subepidermal edema and mixed inflammatory cellular infiltration, which were significantly reduced by the γ-lactone compared to the positive control (p-value = 0.00013). Diuretic and toxicity studies of oral γ-lactone-MC-NPs were performed. No diuretic activity was observed. However, lethargy, drowsiness, and refusal to feeding observed may limit its oral administration.     

Biotransformation of phorbol by human intestinal bacteria

Anaerobic incubation of phorbol (1) from Croton tiglium with human intestinal bacteria afforded five metabolites: isophorbol (2), deoxyphorbol (3), 4beta,9alpha,20-trihydroxy-13,15-seco-1,6,15-tigliatriene-3,13-dione (4), 4beta,9alpha,20-trihydroxy-15,16,17-trinor-1,6-tigliadiene-3,13-dione (5) and 4beta,9a,20-trihydroxy-14(13-->12)-abeo-12alphaH-1,6-tigliadiene-3,13-dione (6). All these metabolites (2-6) were identified and characterized by spectroscopic means, including two-dimensional (2D)-NMR. Nine defined strains from the human intestine showed an ability to transform 1 to these metabolites.     

Antianexiety activity of pyridine derivatives synthesized from 2-chloro-6-hydrazino-isonicotinic acid hydrazide

A series of oxadiazole pyridine derivatives were synthesized by using 2-chloro-6-hydrazinoisonicotinic acid hydrazide as starting material. Treatment of the hydrazide with carbon disulfide to afford the oxadiazole derivative, which was treated with 5-methyl-2-furancarbaldehyde, formic acid, acetic acid/acetic anhydride, or phthalic anhydride to yield the corresponding pyridinodiazoles and on imide. Condensation of the hydrazide with p-fluorobenzaldehyde in ethanol or acetic acid in the presence of sodium acetate afforded hydrazone and oxadiazole derivatives, which were acetylated and cyclized with acetic anhydride to N-acetyloxadiazole derivatives. The hydrazone was treated with acetic acid in the presence of sodium acetate, or bromine water/sodium acetate to give on oxadiazole, while it was cyclized with chloroacetyl chloride in the presence of TEA to oxoazetidinaminoisonicotinamide. Finally, condensation of the hydrazide with acid anhydrides in refluxing glacial acetic acid afforded the corresponding bisimide derivatives. The pharmacological screening showed that many of these obtained compounds have good antianexiety activity comparable to diazepam^® as positive control.     

Synthesis,Spectroscopy, and Anticancer Activity of Two New Nanoscale Au(III) N4 Schiff Base Complexes

Russian Journal of General Chemistry - Mononuclear Au(III) Schiff base complexes are synthesized by the reaction of 4-aminoantipyrine with hydrazine. The chemical structures of new Schiff bases and...     

Selenium-Containing Heterocycles: Synthetic Investigation of 3-Amino-2-Ethylselenopyridine Carboxylate Using Sodium Borohydride

3-amino-4,6-dimethyl-2-ethylseleno[2,3-b]pyridine carboxylate (5) was prepared by a reaction of dipyridyl diselenide derivative (3) with sodium borohydride as a reducing agent followed by α-haloester. The reaction of 5 with hydrazine hydrate afforded the corresponding carbohydrazide 8. The benzylidene derivative 9 provided novel heterocycles of pyrimidoseleno pyridine and thiazinoseleno pyridine derivatives (10–12), upon treatment with triethylorthoformate, acetic anhydride, and carbon disulfide, respectively.     

Selenium-Containing Heterocycles. Synthesis and Reactions of 2-Amino-4,5,6,7-tetrahydro-1-benzoselenophene-3-carbonitrile with Anticipated Biological Activity

Reaction of 2-amino-4,5,6,7-tetrahydro-1-benzoselenophene-3-carbonitrile with ethylenediamine in the presence of a catalytic amount of carbon disulfide afforded 2-amino-3-(4,5-dihydro-1H-imidazol-2-yl)-4,5,6,7-tetrahydro-1-benzoselenophene. Cyclocondensation of the latter with triethyl orthoformate, benzaldehyde, and carbon disulfide gave tetracyclic imidazobenzoselenophenopyrimidine derivatives. Treatment of 2,3,5,6,8,9,10,11-octahydroimidazo[2,1-c][1]benzoselenopheno[3,2-e]pyrimidine-5-thione with hydrazine hydrate led to the corresponding 5-hydrazino derivative whose reactions with triethyl orthoformate and sodium nitrite were accompanied by closure of 1,2,4-triazole and tetrazole rings, respectively. Fused benzoseleno-phenopyrimidine systems were also obtained by reaction of 2-amino-4,5,6,7-tetrahydrobenzo-1-selenophene-3-carbonitrile with formamide, carbon disulfide, and phenyl isothiocyanate. Some newly synthesized compounds were tested for antimicrobial and antifungal activity.__________From Zhurnal Organicheskoi Khimii, Vol. 41, No. 3, 2005, pp. 406–410.Original English Text Copyright © 2005 by Abdel-Hafez.The original article was submitted in English.This study was presented at the 7th IUPAC International Conference on Heteroatom Chemistry (ICHAC-7), Shanghai, August 20–25, 2004.     

Inhibition of cytopathic effect of human immunodeficiency virus type-1 by various phorbol derivatives

Forty-eight derivatives of phorbol (9) and isophorbol (14) were evaluated for their inhibition of human immunodeficiency virus (HIV)-1 induced cytopathic effects (CPE) on MT-4 cells, as well as their activation of protein kinase C (PKC), as indices of anti-HIV-1 and tumor promoting activities, respectively. Of these compounds, the most potent inhibition of CPE was observed in 12-O-tetradecanoylphorbol 13-acetate (8) and 12-O-acetylphorbol 13-decanoate (6). The former also showed the strongest PKC activation activity, while the latter showed no activity at 10 ng/ml. Both activities were generally observed in those phorbol derivatives with an A/B trans configuration, but not in the isophorbol derivatives with an A/B cis configuration. Acetylation of 20-OH in the phorbol derivatives significantly reduced the inhibition of CPE, as shown in 12-O-, 20-O-diacetylphorbol 13-decanoate (6a) (IC100=15.6 microg/ml) vs. compound 6 (IC100=0.0076 microg/ml), and 12-O-tetradecanoylphorbol 13,20-diacetate (8a) (IC100=15.6 microg/ml) vs. 12-O-tetradecanoylphorbol 13-acetate (8) (IC100=0.00048 microg/ml), except in the case of 12-O-decanoylphorbol 13-(2-methylbutyrate) (4) and phorbol 12,13-diacetate (9c). The reduction of a carbonyl group at C-3 abruptly reduced the inhibition of CPE, as observed in 3beta-hydroxyphorbol 12,13,20-triacetate (9f) (IC100=500 microg/ml) vs. phorbol 12,13,20-triacetate (9d) (IC100=62.5 microg/ml). Although 8 was equipotent in the inhibition of CPE, and activation of PKC, both activities were abruptly decreased by the acetylation of 20-OH and methylation of 4-OH [as in 8a and 4-O-methyl-12-O-tetradecanoylphorbol 13,20-diacetate (8b), respectively]. On the other hand, its positional isomer (12-O-acetylphorbol 13-tetradecanoate (8c) showed neither activities. The removal of a long acyl group in 8 led to a substantial loss of both activities, as shown in phorbol 13-acetate (9b). Of the 12-O-acetyl-13-O-acylphorbol derivatives, the highest inhibition of CPE was observed in 6, which has a dodecanoyl residue at C-13. Both an increase and decrease in the number of fatty acid carbon chains resulted in significant reduction of the inhibition of CPE.     

Nano-Co3O4-catalyzed microwave-assisted one-pot synthesis of some seleno [2 , 3-b ] pyridine/quinoline derivatives

For the efficient synthesis of transition-metal cobalt oxide nanoparticles (Co₃O₄ NPs) without using any costly and toxic solvent or complicated equipment, the co-precipitation method was used in this work. Using scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDX), UV–Vis spectrophotometry, Fourier-transform infrared spectroscopy (FTIR) and X-ray diffraction (XRD), the prepared Co₃O₄ NPs were characterized and identified. The influence of prepared Co₃O₄ NPs on the developmental synthesis of some selenopyridine/quinoline derivatives under different microwave irradiation powers and irradiation times was investigated via click (reaction) chemistry. The reusable Co₃O₄ nanoparticles have high catalytic activity under microwave irradiation for the synthesis of organoselenium compounds with higher yields (>?90%), milder reaction conditions and shorter time without significantly decreasing the reaction rates and yields.