Functionalised cyclopentadienyl zirconium compounds as potential anticancer drugs

New neutral and ionic functionalised zirconocene dichloride compounds have been isolated and characterised. The ionic zirconocene exhibits excellent cytotoxicity against a range of human tumour cell lines, which represents the first active anticancer zirconocene dichloride compound.     

Functionalised cyclopentadienyl titanium compounds as potential anticancer drugs

A number of new ionic titanocene compounds have been isolated and characterised, which exhibit excellent cytotoxicity against different human tumour cell lines including a defined cisplatin resistant cell line. A range of biological assays have been carried out to determine levels of cytotoxicity and levels of DNA interstrand crosslinking.     

Photodecomposition of several compounds commonly used as sunscreen agents

The photolysis reactions of three compounds commonly used as a sunscreen agents, Parsol 1789 (1-[4-(1,1-dimethylethyl)phenyl]-3-(4-methoxyphenyl)-1,3- propanedione), Oxybenzone ((2-hydroxy-4-methoxyphenyl)phenyl-methanone) and Padimate O (2-ethylhexyl-4-(dimethylamino)benzoate), were investigated to provide a chemical background to aid in the understanding of the photosensitization of the sunscreen agents. Photolysis was carried out in cyclohexane for 70–140 h using a mercury vapor lamp (450W) without excluding oxygen.

Irradation of Parsol 1789 in cyclohexane yielded tert-butylbenzene, p-tert-butylbenzoic acid and p-methoxybenzoic acid; products obtained from the combination of the sunscreen with the solvent included the cyclohexyl esters of p-methoxybenzoic acid, p-tert-butylbenzoic acid and methanoic acid; products obtained from the solvent included cyclohexanol, cyclohexanone and dicyclohexyl ether.

Irradiation of Oxybenzone in the cyclohexane for 100 h produced no detectable products by either gas or liquid chromatographic analysis. Oxybenzone was recovered unchanged and no products were observed from the photoinitiated reaction of oxygen with the solvent.

Irradiation of Padimate O in cyclohexane yielded the ethylhexyl esters of p-aminobenzoic acid, p-monomethylaminobenzoic acid and p-dimethylamino (o/m)-methylbenzoic acid, as well as products from the photoinitiated reaction of oxygen with the solvent.     

Comparative study of the oxidative and thermal stability of vegetable oils to be used as lubricant bases

Demand for lubricating oils is increasing in the growing Brazilian economy. The use of vegetable bases in exchange of minerals can bring socio-economic and environmental benefits for Brazil. The purpose of this study is to compare the thermal and oxidative stability of vegetable oils related to the bases commonly used as lubricants. In this study, thermogravimetric analysis of castor oil, cotton oil, macauba’s almond oil, passion oil, paraffinic mineral oil, naphthenic oil (NH-140) and synthetic oil (Etro) was performed in inert and oxidative atmosphere to study the thermal and oxidative degradation of the vegetable oils related to the most common lubricants’ oils base. These oils’ oxidation stability were determined by standard procedures (ISO 6886). The use of mineral oil’s additives in these vegetable oils was tested to verify the viability of these additives to improve the oxidative stability of the vegetable oils. The castor oil and the cotton oil presented results of thermal analysis similar to the mineral and synthetic bases values. The castor oil was the only vegetable oil that showed a great oxidative stability. All other vegetable oils had their oxidative stability significantly increased by the additives.     

Liquid chromatographic separation of fluoroquinolone antibacterials used as veterinary drugs

Summary A liquid chromatographic method has been developed to separate a series of quinolones which are widely used as veterinary drugs: danofloxacin, difloxacin, enrofloxacin (and its metabolite ciprofloxacin), marbofloxacin, norfloxacin and sarafloxacin. Separation was performed by using an end-capped high-purity silica-based C₈ column and a mobile phase consisting of acetonitrile-aqueous oxalic acid buffer solution. In order to establish the optimal conditions for an isocratic separation, a three-factor Doehlert experimental design was applied. Gradient elution was applied which reduced analysis time. Figures of merit of the method proposed, with fluorimetric detection, were evaluated.     

Determination of drugs used as anti-Parkinson's disease drugs in urine and serum by capillary electrophoresis

A new capillary electrophoresis method to determine simultaneously eight of the most important anti-Parkinson's disease compounds has been developed. The generic names of the drugs studied are benactyzine (BA), trihexyphenidyl (TP), fenpiverin (FP), diphemin (DF), scopolamine (BL), adiphenine (TS), diethylaminoethylester 1-phenylcyclopentane-1-carboxylate (EKK), and diethylaminoethylester tetramethoxydiphenylacetate (EKO). An untreated fused-silica capillary tube (75 microns i.d., 57 cm total length, 49.5 cm length to the detector) was used with detection at 190 nm. The optimal separation conditions were 50 mM phosphate buffer (pH 2.7) with 7 mM-beta-cyclodextrin, electrokinetic injection for 15 sec at 5 kV, temperature 25 degrees C, and 15-20 kV separation voltage. Complete separation of all compounds was achieved in less than 16 min. The procedure was applied for the determination in urine and serum. The limits of detection (LOD, S/N = 3) for serum were 209 (FP), 234 (EKO), 168 (DF), 182 (BA), 168 (TP), 220 (BL), 174 (TS), and 163 (EKK) ppb. The method can be used for the therapeutic drug monitoring of these central active cholinolytics in clinical laboratories.     

New coordination compounds of tin(IV) with Schiff bases of dialdehyde/diketones and sulpha drugs

New tin(IV) complexes have been synthesized by the reaction of dimethyltindichloride with nitrogen donor ligands. The ligands used in these studies were condensation products of dialdehydes/diketones and sulpha drugs. Their structural studies have been carried out on the basis of elemental analyses, ultraviolet, infrared, ¹H-NMR and ¹¹⁹Sn-NMR spectral studies. The monomeric and non-electrolytic nature of these complexes has been confirmed by their molecular weight determination and conductance measurements.     

三唑类药物研究新进展

三唑类化合物作为药物广泛应用于临床,是目前药物研究开发的重点领域之一．越来越多的高活性、低毒性、不良反应少、多药耐药性小、生物利用率高、药代动力学性质好、药物靶向性强、给药方式多样化、广谱、高疗效的三唑类化合物作为候选药物或药物用于临床医治多种疾病,显示出了三唑类化合物在医药领域的巨大开发价值和潜在的宽广应用．本文结合自己的工作,参考国内外近五年文献系统地综述了三唑类化合物作为药物在整个医药领域的研究与开发近况,包括抗真菌、抗细菌、抗结核、抗癌、抗病毒、抗炎镇痛、抗惊厥等,并展望其发展趋势与前景．希望该评论有助于为高活性低毒性三唑类医药合理设计提供新思路．     

Principal component analysis of thermal decomposition of magnesium salts used as drugs

Thermal decomposition of magnesium salts of organic acids used in medicine (Mg acetate, Mg valproate, Mg lactate, Mg citrate, Mg hydrogen aspartate, Zn hydrogen aspartate) was analyzed by thermoanalytical, calorimetrical, and computational methods. Thermoanalytical studies were performed with aid of a derivatograph. 50-, 100-, and 200-mg samples were heated in a static air atmosphere at a heating rate of 3, 5, 10, and 15 °C min⁻¹ up to the final temperature of 700–900 °C. By differential thermal analysis (DTA), thermogravimetry (TG), and derivative thermogravimetry (DTG) methods, it has been established that thermal decomposition of the salts under study occurs via two stages. The first stage (dehydratation) was distinctly marked on the thermoanalytical curves. Calorimetrical studies were carried out by using of a heat-flux Mettler Toledo differential scanning calorimetry (DSC) system. Ten milligram samples of compounds under study were heated in the temperature range from 20 to 400 °C at a heating rate of 10 and 20 °C min⁻¹ under an air stream. The studies showed that the values of transitions heats and enthalpies of dehydration for investigated salts varied with the increasing of heating rate. For chemometric evaluation of thermoanalytical results, the principal component analysis (PCA) was applied. This method revealed that points on PC1 versus PC2 diagrams corresponding to the compounds of similar chemical constitution are localized in the similar ranges of the first two PC’s values. This proves that thermal decomposition reflects similarity in the structure of magnesium salts of organic acids.     

18F used as tracer to study water uptake and transport imaging of a cowpea plant

We present the water uptake ability of cowpea (Vigna unguliculata Walp)which has been regarded as one of the most drought resistant species amongthe pulse crops. It has been suggested that in the lower part of the stem,parenchymatous tissue for storing water has been developed for the functionof drought resistance. We confirmed that in this tissue, water amount washigh compared to the other stems by neutron radiography. Then the water uptakemanner was measured by positron emitting tracer imaging system (PETIS) using ¹⁸F labeled water produced by a cyclotron. Comparing the water uptakemanner of cowpea plant with that of common bean, cowpea plant was found tomaintain high water uptake activity after drying treatment, suggesting thehigh drought resistant character.     

An investigation of phenolic compounds from plant sources as trypsin inhibitors

In the search of new trypsin inhibitors caffeic acid (1), cinnamic acid (2), gallic acid (3) and eugenol (4) from Cinnamomum zeylanicum, ferulic acid (5) from Impatiens bicolor, vanillin (6) from Melia azedarach and catechol (7) from Allium cepa were isolated through bioassay guided fractionation of the plant extracts. IC (50) values of the compounds 1, 2 and 5 were found to be 0.35?±?0.02?mM, 0.96?±?0.05?mM and 1.22?±?0.06?mM, respectively. Lineweaver-Burk and Dixon plots and their secondary replots showed that 1 was non-competitive inhibitor of this enzyme with K(i) value 0.102?±?0.006?mM.     

Bioassay and bioactivity of polymer as carrier for some active compounds such as anticancer drugs

The present work deals with the development of a new slow release polymeric material, based on maize starch/cellulose acetate blend polymerized with acrylic acid monomer by free-radical mechanism. The polymerization was initiated by a redox system. The synthesized polymeric material may be used as a carrier for some active compounds such as anticancer drugs and has been characterized by Fourier transform spectroscopy. The active compounds are a new series of heterocyclic derivatives that had an anticancer effect and were prepared from pyrimidine and coumarin compounds, namely: 7-(2-methoxyphenyl)-5-thioxo-5,6-dihydro[1,2,4]triazolo[4,3-c] pyrimidine-8-carbonitrile (compound I), 8-(2-methoxyphenyl)-3,4-dioxo-6-thioxo-3,4,6,7-tetrahydro-2h-pyrimido[6,1-c]-[1,2,4]triazine-9-carbonitrile (compound II), and 4-substituted-1-(1-(7-methoxy-4-methyl-coumarin-8-yl) ethylidene) thiosemi-carbazide (compound III). They were incorporated into the prepared polymer matrix. The polymer-carried drug was tested for slow release drug delivery through testing it in aqueous media for different time periods and examining it as an anti-proliferative agent against human liver cancer cell line (HEPG2). The release rate of the drug was evaluated in aqueous media at different pHs as well as in dimethyl formamide which is the good solvent of such drugs. The release was measured spectrophotometrically. It was found that the release rate depends on the pH of the aqueous media. The release of the drug in the alkaline media was found to be high compared with other media. Also, the sustained release of the drug was extended to about 20 days. The activity of the released drug against human liver cancer cell line was tested. The results showed that compound (III) gave the highest growth inhibition activity followed by compound (II), while compound (I) indicated the lowest activity against the human liver (HEPG2) cancer cell line.     

Protons as the triggers to regulate hydrogen-bonding receptors

[reaction: see text] The protonation of alkylamines in two novel receptors results in intramolecular host-guest associations between the resulting ammonium ions and crown ether macrocycles. These interactions result in conformational changes of the receptors and prevent them from acting as hydrogen bond complements for uracil and carboxylate guest species.     

Niflumic acid-collagen delivery systems used as anti-inflammatory drugs and analgesics in dentistry

Collagen sponges are known to be safe and well-characterized supports for drug delivery systems. The aim of this study was to prepare, characterize and test drug delivery systems that contain collagen as support and niflumic acid as a drug. Type-I collagen and niflumic acid gels were cross-linked with different concentrations of glutaraldehyde and then freeze-dried in order to obtain collagen matrices (spongious form). The physical-chemical properties were assessed by infrared spectroscopy (FTIR) and morphological properties were evaluated by water absorption. Niflumic acid release from cross-linked collagen spongious forms was also investigated and the kinetic mechanism was discussed.     

Chiral separation of cathinone derivatives used as recreational drugs by cyclodextrin-modified capillary electrophoresis

In recent years, cathinone derivatives have entered the global drug market and caused serious social problems in many European countries. Modification of the basic structure of cathinone leads to a multitude of derivatives, including the most popular representative mephedrone. All those substances contain a stereogenic center and therefore two isoforms exist. As it is the case with many chiral active pharmaceutical ingredients, even the pharmacological effect of the enantiomers of those psychoactive compounds may differ. During this research, an easy-to-prepare chiral capillary zone electrophoresis method for the enantioseparation of a set of 19 cathinone derivatives was developed. Testing different types of cyclodextrin (CD), including native-β-CD, carboxymethyl-β-CD, 2-hydroxypropyl-β-CD, sulfated-β-CD, and native γ-CD, best results were obtained with the negatively charged sulfated-β-CD. The effect of the CD concentration, the temperature, and the addition of ACN to the BGE on the enantioseparation is shown by three model compounds. Under optimal conditions, using 20 mg/mL sulfated-β-CD in 50 mM ammonium acetate buffer pH?= 4.5 containing 10% v/v ACN at a cassette temperature of 40°C and with an applied voltage of 20 kV, all derivatives except methedrone were resolved in their enantiomers within 20 min.     

Lecithin organogels used as bioactive compounds carriers. A microdomain properties investigation

Organogels were obtained by adding small amounts of water to a solution of lecithin in organic solvents. Either isooctane or isopropyl palmitate and isopropyl myristate were used as the continuous organic phase of the gels. EPR spectroscopy using both DSA membrane-sensitive and lipophilic spin probes was applied to define the dynamic structure of the surfactant monolayer and the continuous oil phase of lecithin organogels. It was found that by increasing the water quantity, an increase of the polar head area per lecithin molecule was induced, and as a consequence the total interface expanded. It was found that the use of esters as organic solvents induced a decrease of the size of the dispersed structures. The interconnection of the aqueous microdomains and their dynamics were monitored by both static and time-resolved fluorescence quenching spectroscopy using Ru(bipy)32+ as fluorophore and Fe(CN)63- as quencher. It was found that the rates of inter- and/or intra-micellar exchange of water molecules were very slow because they appeared quite immobilized close to the lecithin polar heads. According to the results of the dynamic studies, appropriate organogels were formulated and used to incorporate model bioactive compounds with medicinal or cosmetic interest such as caffeine and theophylline. When these systems were tested for trans-membrane diffusion, they showed a 24 h permeation of 20% and 35%, respectively.     

Assessment of methods used for predicting lipophilicity: Application to nucleosides and nucleoside bases

Estimating log P (logarithm of “1-octanol to water” partition coefficients) as a measure of lipophilicity for organic compounds is of considerable importance in drug discovery. Several methods have been developed for this purpose, each with its own drawbacks and advantages. In this article, a systematic comparison of three well-documented and fully computerized methods has been attempted for a set of nucleosides and bases. The first method (BLOGP) is based on overall molecular properties derived from a molecular orbital calculation to predict log P. The second method (CLOGP) uses fragmental lipophilicity constants with correction factors and treats log P as an additive-constitutive property. The third method (ALOGP) is based on an additivity scheme of atomic lipophilicity constants, with the constitutive factor governed by an elaborate list of atom types. However, none of these methods take into account conformational flexibility or intramolecular hydrogen bonding, which can cause substantial discrepancy between observations and predictions. A comparison of predictions from each of these methods indicates that the atomic contribution method (ALOGP with r = 0.842 and SD = 0.51) is better than other methods (with r = 0.395 and SD = 1.2 for BLOGP and r = 0.713 and SD = 0.93 for CLOGP) for this class of compounds. Our overall assessment is that we do not have, as yet, a highly reliable, fully computerized log P prediction method applicable to flexible heterocycles such as nucleoside analogs. © John Wiley & Sons, Inc.