maleic-acid and malonic-acid

ST segment elevation myocardial infarction (STEMI) is one of the most common global causes of cardiovascular disease-related death. Several metabolites may change during STEMI. Hence, analysis of metabolites in body fluid may be considered as a rapid and accurate test for initial diagnosis. This study has therefore attempted to determine the variation in metabolites identified in the serum of STEMI patients (n = 20) and 15 controls. Samples collected from the Cardiology Department, Medical Faculty, Ataturk University, were extracted by liquid-liquid extraction and analysed using liquid chromatography quadrupole time-of-flight mass spectrometry. The METLIN database was used for the identification and characterization of metabolites. According to Q-TOF/MS measurements, 231 m/z values, which were significantly different between groups (P < 0.01 and fold analysis >1.5) were detected. Metabolite identification was achieved via the Human Metabolome database. According to the multivariate data analysis, leucine, isoleucine, l-proline, l-alanine, glycine, fumaric acid, citrate, succinate and carnitine levels were decreased, whereas levels of propionic acid, maleic acid, butyric acid, urea, oleic acid, palmitic acid, lysoPC [18:2(9Z)], glycerol, phoshpatidylethanolamine, caffeine and l-lactic acid were increased in STEMI patients compared with controls. In conclusion, malonic acid, maleic acid, fumaric acid and palmitic acid can be used as biomarkers for early risk stratification of patients with STEMI.

Topics: Amino Acids; Chromatography, Liquid; Female; Fumarates; Humans; Male; Maleates; Malonates; Mass Spectrometry; Metabolome; Metabolomics; Middle Aged; ST Elevation Myocardial Infarction

In this work, three polycrystalline materials containing co-crystals of theophylline with malonic, maleic, and glutaric acids were studied using (13)C, (15)N and (1)H solid-state NMR and FT-IR spectroscopy. The NMR assignments were supported by gauge including projector augmented waves (GIPAW) calculations of chemical shielding, performed using X-ray determined geometry. The experimental (13)C cross polarization/magic angle spinning (CP/MAS) NMR results and the calculated isotropic chemical shifts were in excellent agreement. A rapid and convenient method for theophylline co-crystals crystal structure analysis has been proposed for co-crystals, which are potentially new APIs.

Topics: Chemistry, Pharmaceutical; Crystallization; Crystallography, X-Ray; Dicarboxylic Acids; Glutarates; Hydrogen Bonding; Kinetics; Magnetic Resonance Spectroscopy; Maleates; Malonates; Molecular Structure; Spectroscopy, Fourier Transform Infrared; Technology, Pharmaceutical; Theophylline

The inhibition of the beta-carbonic anhydrases (CAs, EC 4.2.1.1) from the pathogenic fungi Cryptococcus neoformans (Can2) and Candida albicans (Nce103) with carboxylates such as the C1-C5 aliphatic carboxylates, oxalate, malonate, maleate, malate, pyruvate, lactate, citrate and some benzoates has been investigated. The best Can2 inhibitors were acetate and maleate (K(I)s of 7.3-8.7 microM), whereas formate, acetate, valerate, oxalate, maleate, citrate and 2,3,5,6-tetrafluorobenzoate showed less effective inhibition, with K(I)s in the range of 42.8-88.6 microM. Propionate, butyrate, malonate, L-malate, pyruvate, L-lactate and benzoate, were weak Can2 inhibitors, with inhibition constants in the range of 225-1267 microM. Nce103 was more susceptible to inhibition with carboxylates compared to Can2, with the best inhibitors (maleate, benzoate, butyrate and malonate) showing K(I)s in the range of 8.6-26.9 microM. L-Malate and pyruvate together with valerate were the less efficient Nce103 inhibitors (K(I)s of 87.7-94.0 microM), while the remaining carboxylates showed a compact behavior of efficient inhibitors (K(I)s in the range of 35.1-61.6 microM). Notably the inhibition profiles of the two fungal beta-CAs was very different from that of the ubiquitous host enzyme hCA II (belonging to the alpha-CA family), with maleate showing selectivity ratios of 113.6 and 115 for Can2 and Nce103, respectively, over hCA II inhibition. Therefore, maleate is a promising starting lead molecule for the development of better, low nanomolar, selective beta-CA inhibitors.

Topics: Acetic Acid; Benzoates; Butyrates; Candida albicans; Carbonic Anhydrase Inhibitors; Carbonic Anhydrases; Carboxylic Acids; Catalytic Domain; Cryptococcus neoformans; Maleates; Malonates; Structure-Activity Relationship; Zinc

Experiments have been performed with a semicontinuous batch reactor to compare the degradation efficiency of nitrobenzene in aqueous solution by the ultrasonic processes of single field, opposite dual fields, and orthogonal dual fields. Ultrasound with dual fields can improve the degradation efficiency of nitrobenzene compared to that of single field, and the improvement phenomenon is even more pronounced in the orthogonal dual-field system. The degradation reactions of nitrobenzene in the three processes all follow the pseudofirst-order kinetic model. The mechanism investigation indicates the degradation proceeds via hydroxyl radical (*OH) oxidation. The enhancement efficiency of orthogonal dual fields is attributed to an obvious synergetic effect, which accelerates the *OH initiation from 0.28 micromol L(-1) min(-1) for a single field to 0.98 micromol L(-1) min(-1) compared with 0.42 micromol L(-1) min(-1) for opposite dual fields, resulting in rapid formation of an increased diversity of byproducts and an advanced degree of mineralization of total organic carbon (TOC). The introduction of an ultrasonic field placed in the different spatial position causes a variable kinetic order during the removal of TOC. The degradation byproducts are identified by gas chromatography mass spectrometry and ion chromatography, including p-, m-nitrophenol, malonic acid, nitrate ion, 4-nitrocatechol, phenol, maleic acid, oxalic acid, hydroquinone, 1,2,3-trihydroxy-5-nitrobenzene, and acetic acid.

Topics: Acetic Acid; Carbon; Catechols; Chromatography, Gas; Hydroquinones; Hydroxyl Radical; Ions; Kinetics; Maleates; Malonates; Nitrates; Nitrobenzenes; Nitrophenols; Oxalic Acid; Ultrasonics; Water

The crystal form adopted by the respiratory drug theophylline was modified using a crystal engineering strategy in order to search for a solid material with improved physical stability. Cocrystals, also referred to as crystalline molecular complexes, were prepared with theophylline and one of several dicarboxylic acids. Four cocrystals of theophylline are reported, one each with oxalic, malonic, maleic and glutaric acids. Crystal structures were obtained for each cocrystal material, allowing an examination of the hydrogen bonding and crystal packing features. The cocrystal design scheme was partly based upon a series of recently reported cocrystals of the molecular analogue, caffeine, and comparisons in packing features are drawn between the two cocrystal series. The theophylline cocrystals were subjected to relative humidity challenges in order to assess their stability in relation to crystalline theophylline anhydrate and the equivalent caffeine cocrystals. None of the cocrystals in this study converted into a hydrated cocrystal upon storage at high relative humidity. Furthermore, the theophylline:oxalic acid cocrystal demonstrated superior humidity stability to theophylline anhydrate under the conditions examined, while the other cocrystals appeared to offer comparable stability to that of theophylline anhydrate. The results demonstrate the feasibility of pharmaceutical cocrystal design based upon the crystallization preferences of a molecular analogue, and furthermore show that avoidance of hydrate formation and improvement in physical stability is possible via pharmaceutical cocrystallization.

Topics: Bronchodilator Agents; Chemistry, Pharmaceutical; Crystallization; Dicarboxylic Acids; Drug Stability; Feasibility Studies; Glutarates; Hydrogen Bonding; Maleates; Malonates; Molecular Structure; Oxalic Acid; Theophylline; Water

Investigations based on computer simulated distributions of histamine in blood plasma were recently devoted to the assessment of the roles of cysteine, aspartic and glutamic acids as possible adjuvants of zinc to favour histamine tissue diffusion through mixed-ligand coordination. Since all tissues contain at least one of the two enzymes required for the catabolism of histamine, any increase of its tissue diffusion is expected to result in an acceleration of its degradation, which may be of interest for the treatment of anaphylactic disorders. As an extension of these studies, the present paper first reports (i) an experimental investigation of the tendency of four dicarboxylic acids, namely malate, malonate, tartrate and maleate, to mixed-ligand coordination with zinc and histamine, (ii) computer-based potential effects to be expected from the association of these agents to zinc with respect to histamine tissue diffusion. Cell culture studies were then used to test simulation expectations. Two series of experiments involving successively human lymphocytes and a lymphoblastoid cell line (8866) have been carried out, which led to the following conclusions: (i) the hypothesis formerly put forward that cysteine could favour histamine tissue diffusion through mixed-ligand coordination with zinc has been validated on the two cell models, (ii) the formerly established suppressive role of histamine versus lymphocyte proliferation has clearly been confirmed, (iii) moreover, this suppressive effect has been shown to occur correlatively to histamine uptake by these cells, (iv) the four dicarboxylic acids, more especially tartric acid, proved effective as catalysts of the two above processes. Possible biomedical applications of these results are discussed.

Topics: Cell Line; Cysteine; Diffusion; Histamine; Humans; Lymphocyte Activation; Lymphocytes; Malates; Maleates; Malonates; Tartrates; Zinc

The spermicidal effect of four organic acids (malonic, maleic, citric and caffeic acids) was evaluated by adding the acids to sperm, and by observing sperm survival and penetration following addition of these acids to human cervical mucus. Direct addition of 0.1% malonic, maleic and citric acid rendered the sperm immotile by a reduction of pH. In capillaries filled with cervical mucus, the incorporation of 0.01% maleic, malonic and citric acids was sufficient to reduce sperm penetration, and at 0.1%, penetration was completely abolished. Thus, malonic, and maleic and citric acids show promise as cervical or vaginal contraceptives. Caffeic acid was found to be unsuitable owing to its insolubility in aqueous media. Electron microscopy indicated that human sperm do not undergo the acrosome reaction while penetrating cervical mucus in vitro.

Topics: Caffeic Acids; Cervix Mucus; Cinnamates; Citrates; Citric Acid; Female; Humans; Male; Maleates; Malonates; Microscopy, Electron; Sperm Motility; Spermatozoa

Topics: Diuretics; Iodoacetates; Maleates; Malonates; Mercuric Chloride; Mercury; Mersalyl; Organomercury Compounds; Phlorhizin