Physico-chemical characterization of disoxaril-dimethyl-beta-cyclodextrin inclusion complex and in vitro permeation studies

In this work we evaluated the ability of 2,6-di-O-methyl-beta-cyclodextrin (DM-beta-Cyd) to include the anti-rhinovirus drug Disoxaril (WIN 51711), increasing its water solubility and stability. The complex, prepared by kneading method, was characterized in the solid state by differential scanning calorimetry and in aqueous solution using circular dichroism and NMR spectroscopy. The formation of 1:1 and 1:2 drug-Cyd complexes was hypothesized. Stability constants for both complexes were determined on the basis of an Ap-type phase solubility diagrams and evidenced a very high stability for the 1:1 complex. Thermodynamic parameters of the binding process showed the existence of classical hydrophobic interactions in the 1:1 complex with the formation of a less ordered system after complexation. An enthalpic contribution rather than an entropic one accompanied the association of the second Cyd molecule. DM-beta-Cyd was able to significantly increase water solubility of WIN 51711, from 0.000123 to 0.47142 mg/ml. Free drug shows a very low water stability, it is completely hydrolyzed after 36 h in PBS (pH 7.0), at 4 degrees C. In the presence of DM-beta-Cyd only a 10% of WIN 51711 was degraded, to the same conditions, after 12 days. DM-beta-Cyd increases the permeation of WIN 51711 across excised bovine nasal mucosa mounted on Franz cells, with respect to the free drug. Nevertheless, the permeation process had a lag time of 2 h so that the drug might assure its pharmacological activity on the outer surface of the mucosa. In vivo studies on rabbits evidenced that WIN 51711 is well tolerated, having no observable effect on the nasal mucosa following repeated administration.     

Effect of hydrodynamic environment on tablet dissolution using flow-through dissolution apparatus

The main objective of this research is to investigate the principles underlying the dissolution process, study the phenomena of drug release in laminar flow, and better understand the effect of hydrodynamic condition on drug dissolution, in order to predict drug dissolution from a solid dosage form. Two drug models were selected, theophylline (Class I) and naproxen (Class II), and were formulated into conventional tablets containing 105 mg theophylline or 300 mg naproxen using wet granulation method. Additionally theophylline (105 mg) and naproxen (300 mg) matrices containing 30% hydroxypropylmethylcellulose (HPMC) polymer were prepared by direct compression and tested for dissolution using both USP II and IV dissolution apparatus. Tablets were tested for dissolution (USP IV) using different cell diameter, flow rate, and different position of the tablet inside the cell. In general, the drug dissolution at a given time is a direct function of the flow rate, increasing the flow rate increases drug release. The use of a small cell resulted in faster drug dissolution and higher Reynold's Number than using a large cell. Tablet position in the cell, also has an effect on drug dissolution, inserting the tablet in a horizontal position inside the cell gave faster dissolution than a vertical position. The hydrodynamic conditions did not affect the drug dissolution from HPMC controlled release tablets indicating that the drug dissolution is controlled by the matrix. An equation to predict drug dissolution from conventional tablets was established: Sh=-21.36+10.58Re(1/2) where R2=0.98. This study demonstrated that hydrodynamic conditions, and type of dissolution testing apparatus used have an effect on dissolution rate, mass transfer rate, and film thickness underlying dissolution process.     

Randomized phase III trial of concurrent chemoradiotherapy vs accelerated hyperfractionation radiotherapy in locally advanced head and neck cancer

The aim of this study was to compare the efficacy and safety of concurrent chemoradiotherapy (CCRT) vs accelerated hyperfractionation with concomitant boost (CCB) as a primary treatment for patients with Stage III–IV squamous cell carcinoma of head and neck (SCCHN). A total of 85 non-metastatic advanced SCCHN patients were accrued from January 2003 to December 2007. Of these, 48 and 37 patients received CCRT and CCB, respectively. The patients were randomized to receive either three cycles of carboplatin and 5-fluorouracil plus conventional radiotherapy (CCRT, 66 Gy in 6.5 weeks) or hybrid accelerated radiotherapy (CCB, 70 Gy in 6 weeks). The primary endpoint was determined by locoregional control rate. The secondary endpoints were overall survival and toxicity. With a median follow-up of 43 months (range, 3–102), the 5-year locoregional control rate was 69.6% in the CCRT arm vs 55.0% in the CCB arm (P = 0.184). The 5-year overall survival rate was marginally significantly different (P = 0.05): 76.1% in the CCRT arm vs 63.5% in the CCB arm. Radiotherapy treatment interruptions of more than three days were 60.4% and 40.5% in the CCRT arm and CCB arm, respectively. The median total treatment time was 55.5 days in the CCRT arm and 49 days in the CCB arm. The rate of Grade 3–4 acute mucositis was significantly higher in the CCB arm (67.6% vs 41.7%, P = 0.01), but no high grade hematologic toxicities were found in the CCB arm (27.2% vs 0%). CCRT has shown a trend of improving outcome over CCB irradiation in locoregionally advanced head and neck cancer.     

Agrimonia pilosa Ledeb., Cinnamomum cassia Blume,and Lonicera japonica Thunb. protect against cognitive dysfunction and energy and glucose dysregulation by reducing neuroinflammation and hippocampal insulin resistance in β-amyloid-infused rats

Objectives: The water extracts of Cinnamomum cassia Blume bark (CCB; Lauraceae), Lonicera japonica Thunb. flower (LJT; Caprifoliaceae), and Agrimonia pilosa Ledeb. leaves (APL; Rosaceae) prevented amyloid-β (25–35)-induced cell death in PC12 cells in our preliminary study. We evaluated whether long-term oral consumption of CCB, LJT, and APL improves cognitive dysfunction and glucose homeostasis in rats with experimentally induced AD-type dementia.

Methods: Male rats received hippocampal CA1 infusions of amyloid-β (25–35, AD) or amyloid-β (35–25, non-plaque forming, normal-controls, Non-AD-CON), at a rate of 3.6?nmol/day for 14 days. AD rats were divided into four groups receiving either 2% lyophilized water extracts of CCB, LJT, or APL or 2% dextrin (AD-CON) in high-fat diets (43% energy as fat).

Results: Hippocampal amyloid-β deposition, tau phosphorylation, and expressions of tumor necrosis factor (TNF)-α and inducible nitric oxide synthase (iNOS) (neruoinflammation markers) were increased, and insulin signaling decreased in AD-CON. CCB, LJT, and APL all prevented hippocampal amyloid-β accumulation and enhanced hippocampal insulin signaling. CCB, LJT, and APL decreased TNF-α and iNOS in the hippocampus and especially APL exhibited the greatest decrease. AD-CON exhibited cognitive dysfunction in passive avoidance and water maze tests, whereas CCB, LJT, and APL protected against cognitive dysfunction, and APL was most effective and was similar to Non-AD-CON. AD-CON had less fat oxidation as an energy fuel, but it was reversed by CCB, LJT, and especially APL. APL-treated rats had less visceral fat than AD-CON rats. AD-CON rats exhibited impaired insulin sensitivity and increased insulin secretion during oral glucose tolerance test compared with Non-AD-CON, but CCB and APL prevented the impairment.

Discussion: These results supported that APL, LJT, and CCB effectively prevent the cognitive dysfunction and the impairment of energy and glucose homeostasis induced by amyloid-β deposition by reducing neuroinflammation and enhancing insulin signaling. APL exhibited the greatest effectiveness for improving cognitive function.     

重庆市某社区卫生服务中心门诊高血压患者用药情况分析

目的分析重庆市某社区卫生服务中心门诊高血压患者用药情况,为指导社区高血压患者合理用药提供依据。方法收集2018年1-12月重庆市某社区卫生服务中心门诊处方(临床诊断为高血压的处方)3779张,对抗高血压药的应用品种、销售金额、用药频度(DDDs)、日均费用(DDC)及药物联用情况等进行统计分析。结果所有处方共涉及843例高血压患者,其中男性358人,女性485人;年龄范围31~97岁。55岁以上的中老年患者共740人(87.79%)。抗高血压药物中销售金额最高的为钙通道阻滞剂(CCB)类(54.66%),其次为血管紧张素Ⅱ受体阻断剂(ARB)类(38.67%)。DDDs排序居前3位的药品分别为苯磺酸左旋氨氯地平片、坎地沙坦酯片和替米沙坦片。在843例患者降压药的使用中,单一用药386例(45.79%),二联用药336例(39.86%),三联用药36例(4.27%)。在二联降压治疗中,以CCB和ARB联用为主(82.73%)。在三联降压治疗中,以CCB+ARB+β受体阻断剂(β-RB)联用为主(52.78%)。结论该社区门诊抗高血压药物应用种类及降压治疗方案使用基本合理,但在考虑用药的经济性方面欠佳,多药联用方案仍需进一步进行规范。此外,临床药师对社区高血压患者进行合理用药宣教时,应重点关注CCB及ARB类药物的使用情况,特别注意潜在的药物相互作用,以降低药物不良反应发生率,提高患者用药依从性。     

In vitro dissolution of respirable aerosols of industrial uranium and plutonium mixed-oxide nuclear fuels

Dissolution characteristics of mixed-oxide nuclear fuels are important considerations for prediction of biological behavior of inhaled particles. Four representative industrial mixed-oxide powders were obtained from fuel fabrication enclosures. Studies of the dissolution of Pu, Am and U from aerosol particles of these materials in a serum simulant solution and in 0.1M HCl showed: (1) dissolution occurred at a rapid rate initially and slowed at longer times, (2) greater percentages of U dissolved than Pu or Am: with the dissolution rates of U and Pu generally reflecting the physical nature of the UO2-PuO2 matrix, (3) the temperature history of industrial mixed-oxides could not be reliably related to Pu dissolution except for a 3-5% increase when incorporated into a solid solution by sintering at 1750 degrees C, and (4) dissolution in the serum simulant agreed with the in vivo UO2 dissolution rate and suggested the dominant role of mechanical processes in PuO2 clearance from the lung. The rapid initial dissolution rate was shown to be related, in part, to an altered surface layer. The advantages and uses of in vitro solubility data for estimation of biological behavior of inhaled industrial mixed oxides, such as assessing the use of chelation therapy and interpretation of urinary excretion data, are discussed. It was concluded that in vitro solubility tests were useful, simple and easily applied to individual materials potentially inhaled by humans.     

Comparative study of copper(II)-curcumin complexes as superoxide dismutase mimics and free radical scavengers

Two stoichiometrically different copper(II) complexes of curcumin (stoichiometry, 1:1 and 1:2 for copper:curcumin), were examined for their superoxide dismutase (SOD) activity, free radical-scavenging ability and antioxidant potential. Both the complexes are soluble in lipids and DMSO. The formation constants of the complexes were determined by voltammetry. EPR spectra of the complexes in DMSO at 77K showed that the 1:2 Cu(II)-curcumin complex is square planar and the 1:1 Cu(II)-curcumin complex is distorted orthorhombic. Cu(II)-curcumin complex (1:1) with larger distortion from square planar structure shows higher SOD activity. These complexes inhibit gamma-radiation induced lipid peroxidation in liposomes and react with DPPH acting as free radical scavengers. One-electron oxidation of the two complexes by radiolytically generated azide radicals in Tx-100 micellar solutions produced phenoxyl radicals, indicating that the phenolic moiety of curcumin in the complexes participates in free radical reactions. Depending on the structure, these two complexes possess different SOD activities, free radical neutralizing abilities and antioxidant potentials. In addition, quantum chemical calculations with density functional theory have been performed to support the experimental observations.     

Perspectives from the frontlines: palliative care providers’ expectations of Canada’s compassionate care benefit programme

Recognising their valuable role as key informants, this study examines the perspectives of front‐line palliative care providers (FLPCP) regarding a social benefit programme in Canada designed to support family caregivers at end‐of‐life, namely the Compassionate Care Benefit (CCB). The CCB’s purpose is to provide income assistance and job security to family caregivers who take temporary leave from employment to care for a dying family member. Contributing to an evaluative study that aims to provide policy‐relevant recommendations about the CCB, this analysis draws on semi‐structured interviews undertaken in 2007/2008 with FLPCPs (n = 50) from across Canada. Although participants were not explicitly asked during interviews about their expectations of the CCB, thematic content analysis revealed ‘expectations’ as a key finding. Through participants’ discussions of their knowledge of and familiarity with the CCB, specific expectations were identified and grouped into four categories: (1) temporal; (2) financial; (3) informational; and (4) administrative. Findings demonstrate that participants expect the CCB to provide: (1) an adequate length of leave time from work, which is reflective of the uncertain nature of caregiving at end‐of‐life; (2) adequate financial support; (3) information on the programme to be disseminated to FLPCPs so that they may share it with others; and (4) a simple, clear, and quick application process. FLPCPs hold unique expertise, and ultimately the power to shape uptake of the CCB. As such, their expectations of the CCB contribute valuable knowledge from which relevant policy recommendations can be made to better meet the needs of family caregivers and FLPCPs alike.     

Dosimetry of metal tritide particles as evaluated by the ICRP 66 model and a biokinetic model from laboratory rats

Internal radiation from inhalation of metal tritide aerosols may present a significant radiation protection problem for nuclear facility workers. Dose was evaluated for three metal tritides: hafnium, titanium, and zirconium. The study included in vitro and in vivo exposures. The inhalation doses for the three materials were calculated by using the ICRP 66 lung model. The doses also were evaluated by a biokinetic model, which was developed according to the results of animal studies. Results showed that the hafnium tritide particles were the most dense but they had a lower dissolution rate and a higher retention rate. Among these three tritides, hafnium was classified as a Type S material according to the ICRP 66 publication, whereas titanium and zirconium ranked between Type M and F materials. The dissolution rate of hafnium tritide appeared to agree well with the in vitro and in vivo studies. The dissolution rates of the other two materials in the in vitro studies were a little higher than those of the in vivo studies. The doses calculated by the ICRP 66 model for all materials were approximately two orders smaller than the doses obtained by the animal studies. This bias was caused by the different intake methods of the ICRP 66 model (inhalation) and in the animal study (instillation). The doses were on the same order while correcting for deposition fractions. The effective doses for hafnium, titanium, and zirconium tritides were 5.43 x 10(-10), 9.05 x 10(-11), and 6.5 x 10(-10) Sv Bq(-1), respectively, according to the animal studies.     

Synthesis and antiamoebic activity of new 1-N-substituted thiocarbamoyl-3,5-diphenyl-2-pyrazoline derivatives and their Pd(II) complexes

Some 1-N-substituted thiocarbamoyl-3,5-diphenyl-2-pyrazoline derivatives (L), 1-8 were synthesized by a base-catalyzed Claisen-Schmidt condensation of benzaldehyde with acetophenone followed by cyclization with various N-4 substituted thiosemicarbazides. The palladium(II) complexes [PdLCl2], 1a-8a of these ligands were obtained by reacting them with [Pd(DMSO)2Cl2]. All compounds have been characterized by means of elemental analyses, electronic, IR, 1H NMR and mass spectroscopic data, while the complexes have additionally been characterized by thermogravimetric patterns. The in vitro antiamoebic activity was evaluated against the HM1:IMSS strain of Entamoeba histolytica and the results were compared with the standard drug, metronidazole. The preliminary test results showed that the complexes had better antiamoebic activity than their respective ligands. Moreover, the complexes showed better inhibition of the test organism. The results suggest that the ligands 4, 7 and the complexes 2a-4a, 6a-8a were found with IC50 lower than that of the standard drug metronidazole and thus are better inhibitor of growth of E. histolytica.     

Feasibility of using recipients of health promotional newsletters for post-marketing surveillance

Achieving an adequate sample size is one of the major difficulties in performing post-marketing observational studies of health outcomes in persons taking specific drug preparations. We assessed the feasibility of recruiting participants for such a study of Cardizem CD from approximately 400,000 U.S. recipients of a health promotion newsletter. A three-page questionnaire was sent to a 2.5% random sample (n = 10,000) of recipients, stratified by geographic region. After two mailings, 2779 (28%) returned the questionnaire. Of the 2779 respondents, 2132 (77%) reported having high blood pressure. Eighty-seven percent indicated a willingness to participate in a long-term prospective study. In a multivariate model, calcium channel blocker (CCB) use was associated with a history of coronary heart disease, duration of hypertension medication use greater than 1 year, a rating of good or excellent hypertension care, higher systolic blood pressure, higher education level, family history of cardiovascular disease, and history of smoking. These results indicate that self-reported CCB users may be at greater risk of cardiovascular heart disease and that it is feasible to use health promotion newsletters as a source of participants in prospective studies of cardiovascular disease.     

Synthesis and anticancer activity of lipophilic platinum(II) complexes of 3,5-diisopropylsalicylate

Novel lipophilic platinum(II) complexes (LSPt-1-3), containing 3,5-diisopropylsalicylate (DIPS) as a leaving group and 2NH(3) or 1R,2R-diaminocyclohexane or (4R,5R)-4,5-bis(aminomethyl)-2-isopropyl-1,3-dioxolane as the carrier, have been synthesized, characterized and evaluated in vitro and in vivo. The octanol/water distribution coefficient of the complexes has also been measured. The results showed that the complexes achieved a typical square planar and the octanol/water distribution coefficient logP was 4.27, 4.37 and 4.31. The complexes were tested by SRB method to be more cytotoxic than Carboplatin, Oxaliplatin and Eptaplatin against 3AO, A549, NCI-H460 and SGC-7901 human cancer cell lines. Among complexes, LSPt-2 was much more effective than Carboplatin and Oxaliplatin in treating the NCI-H460 non-small-cell lung tumor-bearing mice. Its optimal activity was 38.8% (T/C) at a dose of 30 mg/kg following i.p. administration. LD(50) for the complex was found to be 230.9 mg/kg. LSPt-2 exhibited great anticancer activity, good lipophilic ability and low toxicity and therefore, it is a promising candidate for effective and stable pharmaceutical liposomal platinum anticancer drug.     

Permeation through five commercially available glove materials by two pentachlorophenol formulations

Five glove materials were tested for permeation by two commonly used formulations of pentachlorophenol (PCP). Permeation was conducted using the method used in two prior studies by NIOSH. The lower limit of PCP quantitation in the receiving side of the permeation cell was 70 parts per billion (ppb). When challenged with a 4.3% PCP in diesel oil solution, both the Dayton Flexible Products Triflex (PVC) and the Best 64 NFW (natural rubber) gloves exhibited breakthrough times thirty seconds after exposure. The Playtex #835 (latex/neoprene) glove exhibited breakthrough after sixty minutes, but showed a five fold greater rate of permeation than the Dayton and the Best glove. Neither the Edmont Sol-Vex (nitrile rubber) nor the Granet Glo-Gluv (PVC) gloves had been permeated after testing for 8 and 16 hours respectively. Following challenge with a 4.2% sodium pentachlorophenate solution, only the Best (natural rubber) glove allowed breakthrough; this only thirty seconds after exposure. Neither the Dayton (5 hours), Playtex (7.5 hours), Edmont (15.5 hours), nor Granet (15.5 hours) gloves had been permeated following completion of testing after the listed duration. This study has shown that different gloves offer differing resistance to permeation by PCP based upon the composition of the glove and the PCP formulation tested.     

山东省部分艾滋病患者抗病毒治疗效果及耐药性研究

目的了解山东省艾滋病患者高效抗逆转录病毒治疗（HAART）效果和病例中HIV-1耐药毒株的出现情况及其对治疗产生的影响。方法于2004、2005年分别对治疗和未接受抗病毒治疗的HIV感染人群进行2次横断面调查。对接受调查者经知情同意，进行个人访谈填写耐药性研究调查表并进行免疫学、病毒学实验室指标评价和服药依从性调查；测定CD4^＋T淋巴细胞计数、血浆病毒载量（VL）；用RT-PCR方法扩增HIV-POL区基因，进行基因型耐药性分析。结果正在接受治疗的艾滋病患者31例，未治疗的27例，2年内分别有83．3％、64．5％的治疗患者CD4^＋T淋巴细胞计数〉350个／μl，分别有45．8％、45．2％的治疗患者VL达到检测限以下，与未治疗组的差异有统计学意义。治疗组患者中出现7个耐药位点，未治疗组出现4个耐药位点，高度耐药突变率及总耐药性突变率前者远高于后者。结论抗病毒治疗患者大部分达到了病毒抑制和免疫重建的目的，症状得到明显好转，治疗患者中出现HIV耐药性毒株，但对总体治疗效果影响不大。     

Synthesis, antiproliferative activity and DNA binding study of mixed ammine/cyclohexylamine platinum(II) complexes with 1-(substituted benzyl) azetidine-3, 3-dicarboxylates

A novel series of ammine/cyclohexylamine platinum(II) complexes with 1-(substituted benzyl) azetidine-3, 3-dicarboxylates as leaving groups have been synthesized and characterized. All complexes were characterized by elemental analysis, IR, ¹H NMR, and ESI-MS spectra. The in vitro antiproliferative activities of the platinum-based compounds have been investigated against several human cancer cell lines, indicating that complexes 1 and 11 showed comparable cytotoxicity to those of cisplatin and oxaliplatin against four cell lines, superior to that of carboplatin. The results of drug safety evaluation (acute toxicity study) showed that complex 11 was much less toxic than cisplatin and oxaliplatin. Flow cytometry and agarose gel electrophoresis studies revealed that both complexes 1 and 11 induced apoptosis of tumor cells and demonstrated the binding affinity of complexes with pET22b plasmid DNA.     

Evaluation of the Mechanical Properties and Drug Permeability of Chitosan/Eudragit RL Composite Film

Objectives

The aim of this study was to design and evaluate a chitosan-based film that has properties required for successful wound dressing, and can control drug penetration and maintenance time in the location.

Methods

Several formulations of a film containing chitosan (3%) and different concentrations of Eudragit RL (0.5%, 1%, and 1.5%) were prepared using the casting/solvent evaporating technique. Mechanical properties, water vapor transmission rate (WVTR), oxygen permeability, water uptake, and nitrofurazone permeability through the films were investigated.

Results

The study results showed that by increasing the Eudragit RL content of composite films, their thickness and tensile strength were enhanced, while their elongation was decreased. No significant difference was observed between the oxygen permeability, WVTR, and water uptake results of pure chitosan films and different composite films containing Eudragit RL. Nitrofurazone permeability of chitosan films was increased by the inclusion of Eudragit RL in composite films, while by increasing the concentration of Eudragit RL, the permeation rate of drug was decreased.

Conclusion

In conclusion, addition of Eudragit RL can improve mechanical properties of chitosan films without any undesirable effect on their water uptake, oxygen permeability, and WVTR qualities. The permeation rate of drugs through the composite films can be modified by changing Eudragit RL/chitosan ratio.     

Syntheses, characterization and in vitro antiamoebic activity of new Pd(II) complexes with 1-N-substituted thiocarbamoyl-3,5-diphenyl-2-pyrazoline derivatives

Reaction of neutral NS bidentate ligands, 1-N-substituted thiocarbamoyl-3,5-diphenyl-2-pyrazolines, isolated by cyclization of chalcone with N-4-substituted thiosemicarbazide of aromatic amines (1-8), with [Pd(DMSO)(2)Cl(2)] (DMSO=dimethylsulfoxide) leads to the formation of new complexes of the type [Pd(L)Cl(2)] (1a-8a). The structures of the compounds were elucidated by UV, IR, (1)H NMR, (13)C NMR and ESI-MS spectral data and thermogravimetric analysis and their purities were confirmed by elemental analyses. The antiamoebic activity of these complexes was evaluated by microdilution method against HM1:IMSS strain of Entameoba histolytica and the results were compared with the standard drug, metronidazole. Generally palladium complexes showed better activity than their corresponding ligands. Compound 3a showed better IC(50)=0.05 microM as compared to metronidazole IC(50)=1.82 microM.     

Synthesis, antibacterial, antifungal activity and interaction of CT-DNA with a new benzimidazole derived Cu(II) complex

The ligand [C(16)H(10)O(2)N(4)S(2)] L has been synthesized by the condensation reaction of 2-mercaptobenzimidazole and diethyloxalate. The ligand L was allowed to react with bis(ethylenediamine)Cu(II)/Ni(II) complexes to yield [C(20)H(22)N(8)S(2)Cu]Cl(2)1 and [C(20)H(22)N(8)S(2)Ni]Cl(2)2 complexes. The Ni(II) complex was synthesized only to elucidate the structure of the complex. The complexes 1 and 2 were characterized by elemental analyses, IR, NMR, EPR, UV-vis spectroscopy and molar conductance measurements. Both the complexes are ionic in nature and possess square-planar geometry. The binding of the complex 1 to calf thymus DNA was investigated spectrophotometrically. The absorption spectra of complex 1 exhibits a slight red shift with "hyperchromic effect" in presence of CTDNA. Electrochemical analysis and viscosity measurements were also carried out to ascertain the mode of binding. The complex 1 in the absence and in presence of CT DNA in aqueous solution exhibits one quasi-reversible redox wave corresponding to Cu(II)/Cu(I) redox couple at a scan rate of 0.2 V s(-1). The shift in DeltaE(p), E(1/2) and I(pa)/I(pc) values ascertain the interaction of calf thymus DNA with copper(II) complex. There is decrease in viscosity of CTDNA which indicates that the complex 1 binds to CTDNA through a partial intercalative mode. The antibacterial and antifungal studies of the [C(7)H(6)N(2)S], [C(4)H(16)N(4)Cu]Cl(2,) [C(16)H(10)N(4)S(2)O(2)] and [C(20)H(22)N(8)S(2)Cu]Cl(2) were carried out against S. aureus, E. coli and A. niger. All the results reveal that the complex 1 is highly active against the bacterial strains and also inhibits fungal growth.     

Cytotoxic activity of new cerium (III) complexes of bis-coumarins

Complexes of cerium (III) with bis-coumarins: 3,3'-benzylidene-bis(4-hydroxy-2H-1-benzopyran-2-one) and bis(4-hydroxy-2-oxo-2H-chromen-3-yl)-(1H-pyrazol-3-yl)-methane were synthesized by reaction of cerium (III) salt and the ligands, in amounts equal to metal/ligand molar ratio of 1:2. The complexes were prepared by adding an aqueous solution of cerium (III) salt to an aqueous solution of the ligand subsequently raising the pH of the mixture gradually to ca. 5.0 by adding dilute solution of sodium hydroxide. The cerium (III) complexes with bis-coumarins were characterized by different physicochemical methods--elemental analysis, IR-, 1H- and 13C-NMR-spectroscopies and mass-spectral data. The spectral data of cerium (III) complexes were interpreted on the basis of comparison with the spectra of the free ligands. This analysis showed that in the Ce (III) complexes the ligands coordinated to the metal ion through both deprotonated hydroxyl groups. On the basis of the nu(C=O) red shift observed, participation of the carbonyl groups in the coordination to the metal ion was also suggested. Cytotoxic screening by MTT assay was carried out. In the present study we performed comparative evaluation of the cytotoxic effects of the two newly synthesized cerium complexes against the acute myeloid leukemia derived HL-60 and the chronic myeloid leukemia (CML)-derived BV-173. In addition the cytotoxic effects of Ce (III) complex with 3,3'-benzylidene-bis(4-hydroxy-2H-1-benzopyran-2-one) were evaluated on the CML-derived K-562 and LAMA-84 cells, characterized by relative low responsiveness to chemotherapy. The DNA isolated from the cytosolic fraction of BV-173 cells after 24 h treatment with the same complex (at 100 and 200 microM) demonstrated a laddering phenomenon that is indicative for apoptotic cell death.