Evaluation of thermal stability and parameters of dissolution of nifedipine crystals

Nifedipine is a calcium channel blocker as well as a powerful vasodilator used to treat ischemic heart disease and hypertension. Its photosensitivity and very low solubility in water have been widely acknowledged as important properties deserving improvements. The main thrust of this study is to characterize the nature and the solid-state of nifedipine crystals obtained using different solvents as well as assess the stability by thermal methods (TG and DSC) and crystals structure by means of spectroscopic techniques (MID FTIR and XRD) and assess the dissolution parameters for such crystals. The calculated kinetic parameters activation energy (E _a = 123.3 kJ mol^?1 ± 0.1), the factor frequency (A = 25.93 ± 0.9 min^?1), and the reaction order (n = 0.2) of the main stage of thermal decomposition of nifedipine raw material were performed according to the Ozawa model. The data showed a zero-order kinetic behavior for all crystals despite the different values of E _a and A. The dissolution profiles were obtained for such crystals in three dissolution media with different pH values. After 1 h of dissolution, the higher amount of nifedipine dissolved was observed for crystals obtained in isopropyl alcohol (52.5 %, pH 4.5), followed by those in chloroform (48.1 %, pH 1.2) and subsequently in acetone (32.5 %, pH 6.8). Results showed different thermal stabilities and significant variations in the solubility of the crystals.     

Synthesis and structural characterization of a zinc(II) complex of the mycobactericidal drug isoniazid - Toxicity against Artemia salina

A new zinc(II) complex of the mycobactericidal drug isoniazid (complex 1) was synthesized and characterized by XRD, vibrational spectroscopy (IR, Raman) and thermogravimetric analysis. The complex is constituted by two isoniazid (INH) molecules, six hydration water molecules and two perchlorate counter-ions for each metal center (C₁₂H₂₆N₆Cl₂O₁₆Zn). Zinc(II) adopts a distorted octahedral geometry, where two INH molecules coordinate in a bidentate manner through the hydrazide group (N, O) and the other two isoniazid residues complete the coordination sphere of zinc(II) through their aromatic nitrogen atoms. This coordination pattern gives rise to a 2-D coordination polymer. Complex 1 belongs to the monoclinic system [a = 8.1190(2) Å, b = 17.977(4) Å, c = 9.1051(2) Å and β = 100.87(3)°], space group P2₁. A biological assay with Artemia salina was also performed. Complex 1 is almost 8.5 times more active than the free ligand. Its toxicity against A. salina correlates well with the cytotoxic activity for some human solid tumors. Therefore, antitumoral properties could be expected from complex 1.     

Macrocyclic multicenter complexes of nickel and copper of increasing complexity

Multicenter (bi-, tri-, and tetranuclear) tetraazamacrocyclic complexes were self-assembled from Ni and Cu tetraazamacrocyclic mononuclear units and α,ω-diamines as building blocks. The structures of all compounds studied were proved by spectroscopic methods (ESI MS and NMR spectroscopy). Electrochemical experiments revealed reversible one-electron electrode processes at each of the Ni(2+) and Cu(2+) centers with formation of metal cations in oxidation state +3. Long linkers allow bi- and trinuclear complexes with noninteracting metal centers to be obtained. In the case of the short linkers (e.g. ethylenediamine) higher, trinuclear species are formed as major product. The structures of the bis- and tris-macrocyclic systems were confirmed by single-crystal X-ray diffraction. The tris-macrocyclic systems form cations in the shape of triangles partially filled with counterions and solvent molecules. The cations form positively charged layers, which interact in the crystal lattice with the neighboring negatively charged layers of anions. In solution, the trinuclear complexes exhibit strong host-guest interactions with 9,10-dimethyltriptycene due to complementarity of shape and size of this guest molecule. The association constants were determined by NMR spectroscopy and voltammetry, and very good agreement was obtained. The structural flexibility of the tetranuclear complex with long linkers allows for attractive interactions between the metal-complexing macrocycles that result in folding of the molecule. On the contrary, no folding is possible in the case of short linkers consisting of two CH(2) groups.     

Comparison between otoacoustic and auditory brainstem response latencies supports slow backward propagation of otoacoustic emissions

Experimental measurements of the latency of transient evoked otoacoustic emission and auditory brainstem responses are compared, to discriminate between different cochlear models for the backward acoustic propagation of otoacoustic emissions. In most transmission-line cochlear models otoacoustic emissions propagate towards the base as a slow transverse traveling wave, whereas other models assume fast backward propagation via longitudinal compression waves in the fluid. Recently, sensitive measurements of the basilar membrane motion have cast serious doubts on the existence of slow backward traveling waves associated with distortion product otoacoustic emissions [He et al., Hear. Res. 228, 112-122 (2007)]. On the other hand, recent analyses of "Allen-Fahey" experiments suggest instead that the slow mechanism transports most of the otoacoustic energy [Shera et al., J. Acoust. Soc. Am. 122, 1564-1575 (2007)]. The two models can also be discriminated by comparing accurate estimates of the otoacoustic emission latency and of the auditory brainstem response latency. In this study, this comparison is done using human data, partly original, and partly from the literature. The results are inconsistent with fast otoacoustic propagation, and suggest that slow traveling waves on the basilar membrane are indeed the main mechanism for the backward propagation of the otoacoustic energy.     

Multicomponent synthesis of benzoxazinones via tandem Ugi/Mitsunobu reactions: an unexpected cine-substitution

A short (2 steps) synthesis of diverse benzoxazinones by coupling the Ugi multicomponent reaction with an intramolecular Mitsunobu substitution is reported. The cyclization step proceeds via an unexpected cine substitution.     

Evaluation of Anthelmintic and Anti-Inflammatory Activity of 1,2,4-Triazole Derivatives

Parasitic diseases, caused by intestinal helminths, remain a very serious problem in both human and veterinary medicine. While searching for new nematicides we examined a series of 1,2,4-triazole derivatives 9–22, obtained during reactions of N³-substituted amidrazones with itaconic anhydride. Two groups of compounds, 9–16 and 17–22, differed in the position of the double bond on the methacrylic acid moiety. The toxicity of derivatives 9–22 and the anti-inflammatory activity of 12 and 19–22 were studied on peripheral blood mononuclear cells (PBMC). Antiproliferative activity of compounds 12 and 19–22 was tested cytometrically in PBMC cultures stimulated by phytohemagglutinin. The influence of derivatives 12 and 19–22 on the TNF-α, IL-6, IL-10 and IFN-γ production was determined by ELISA in lipopolysaccharide-stimulated PBMC cultures. Anthelmintic activity of compounds 10–22 was studied in the Rhabditis sp. nematodes model. Most compounds (11–22) proved to be non-toxic to human PBMC. Derivatives 19–22 showed anti-inflammatory activity by inhibiting the proliferation of lymphocytes. Moreover, compounds 12 and 19–22 significantly reduced the production of TNF-α and derivatives 19–21 decreased the level of INF-γ. The strongest anti-inflammatory activity was observed for compound 21. Compounds 12 and 14 demonstrated anthelmintic activity higher than albendazole and may become promising candidates for anthelmintic drugs.     

Fiber Preparation from Micronized Oat By-Products: Antioxidant Properties and Interactions between Bioactive Compounds

This study aimed to investigate the possibility of utilizing oat by-products for fiber preparation. Oat husk (OH) and oat bran (OB) were micronized and used to prepare a novel product rich in fiber and with enhanced antioxidant properties. The basic chemical composition and phenolic acid profile were determined in OH and OB. The antioxidant properties of OH and OB were also analyzed. The type and strength of interactions between the biologically active compounds from their mixtures were characterized by an isobolographic analysis. The analyses showed that the sum of phenolic acids was higher in OH than in OB. Ferulic acid was dominant in both OH and OB; however, its content in OH was over sixfold higher than that in OB. The results also suggested that both OH and OB can be used for preparing fiber with enhanced antioxidant properties. The optimal composition of the preparation, with 60–70% of OH and 30–40% of OB, allows for obtaining a product with 60–70% fiber and enhanced antioxidant activity due to bioactive substances and their synergistic effect. The resulting product can be a valuable additive to various food and dietary supplements.     

Are Organic Certified Carrots Richer in Health-Promoting Phenolics and Carotenoids than the Conventionally Grown Ones?

The aim of the present study was to determine the concentrations of polyphenols and carotenoids by means of HPLC/UV-Vis in certified organic and non-organic carrots (Daucus carota L.) of two cultivars (Flacoro and Nantejska). The analyzed carrot root samples contained, on average, 4.29 ± 0.83 mg/100g f.w. of carotenoids (mainly β-carotene) and 9.09 ± 2.97 mg/100g f.w. of polyphenols, including 4.44 ± 1.42 mg/100g f.w. of phenolic acids and 4.65 ± 1.96 mg/100g f.w. of flavonoids. Significant effects of the production system on the carotenoids (total) and β-carotene concentration were found, with higher concentrations of these compounds generally identified in conventionally cultivated roots (4.67 ± 0.88 mg/100g f.w.) vs. organically grown ones (4.08 ± 0.74 mg/100g f.w.). There was a noticeable inter-sample (inter-farm) variation in the concentration of polyphenols in carrot roots. Despite a general trend towards higher concentrations of these compounds in the organic carrots (9.33 ± 3.17 mg/100g f.w.) vs. conventional carrots (8.64 ± 2.58 mg/100g f.w.), and in those of Nantejska (9.60 ± 2.87 mg/100g f.w.) vs. Flacoro (8.46 ± 3.02 mg/100g f.w.) cultivar, no consistent, statistically significant impact of the production system and/or cultivar on the level of these bioactive compounds was identified. More efforts should be encouraged to ensure that organic crops reaching the market consistently contain the expected high levels of health-promoting bioactive compounds, which could be brought through their shelf-life and all processing steps, in order to meet consumers’ expectations and provide the expected health benefits.     

Electrochemical Sulphenylation/Cyclization of Quinones: A Rapid,Green, and Efficient Access to Cytotoxic Compounds

Undivided electrochemical cells enable economical preparation of sulphur-containing naphthoquinones through electrochemical sulphenylation of quinoidal compounds. The environmentally friendly and efficient protocol eliminates the use of chemical oxidants and facilitates the synthesis of the desired molecules. This approach offers an efficient and versatile method to synthesize quinones that exhibit cytotoxicity against cancer cell lines.