Vol 6, No 4 (2015)

December 2015



Table of Contents

Editorial

Hakan Arslan
10.5155/eurjchem.6.4.i-i.1366
Editorial Board
i-i
Hakan Arslan
10.5155/eurjchem.6.4.ii-vi.1367
Graphical Contents
ii-vi

Research Article

La Ode Kadidae, Akira Usami, Tomoya Koyama, Mitsunori Honda, Ko-Ki Kunimoto
10.5155/eurjchem.6.4.367-373.1298

Caffeoylquinic acids (CQAs) are a group of the phenylpropanoids produced by certain plant species, which have various biological activities including antioxidant, antibacterial, anticancer, and others. Several synthetic routes have been developed using quinic acids (QAs) and caffeic acid derivatives as starting materials. In this study, alternative pathways of 3- and 5-CQAs preparation using protected quinic acids are described. Both CQAs were achieved by removal of the protecting groups of compound 9 and 18 with acid hydrolysis using dilute HCl solution. These compounds (9 and 18) are novel, resulted from esterification reaction of diacetyl caffeoyl chloride and protected quinic acids. The hydroxyl groups of quinic acid in this case were protected with 2,2-dimethoxy propane or tert-butyldimethylsilyl (TBS) chloride.

367-373
Wasfi Aboud Al-Masoudi, Rafid Hmedan Al-Asadi, Rasha Munther Othman, Najim Aboud Al‐Masoudi
10.5155/eurjchem.6.4.374-380.1254

A new series of organonotellurium compounds containing azo groups were prepared by new and convenient methods. Reaction of 1-(4-mercuric chloride-2,3-dichlorophenyl)-2-chloro diazine (4) with 8-hydroxyquinoline (5) gave the new organomercury compound 6 in good yield. Telluratio of compound 6 with tellurium tetrabromide in 1:1 and 1:2 mole ratio gave the o-tellurated azo compounds ArTeBr3 (7) and Ar2TeBr2 (9), respectively. Reduction of both ArTeBr3 and Ar2TeBr2 by hydrazine hydrate gave the ditelluride 8, and telluride 10, respectively. The synthesized compounds were screened for their antibacterial activity against Staphylococcus aureus, Escherichia coli, Bacillus subtilis, Klebsiella pneumonia, Salmonella spp., Streptococcus spp. and Bacillus cereus. Additionally, the prepared compounds were tested for antifungal activity against Candida sp., Aspergillus multi and Aspergillus niger. All compounds exhibited good antibacterial and antifungal activity. Computational study of the new compounds was calculated using Gaussian 09 program package. Molecular modeling studies were performed and showed hydrogen binding and hydrophobic interactions.

374-380
Amal Mahmoud Abou Al Alamein
10.5155/eurjchem.6.4.381-386.1296

Stability evaluation of the drug substance is an integral part of the systematic approach to stability studies. Hence, three simple, sensitive and precise methods depending on two different techniques as UV spectrophotometry and chromatography were adopted for the task of stability indicating determination of sertaconazole (SER) in presence of its acidic degradation products. The first method is Zero-crossing first derivative (1D) spectrophotometric one, which allows the determination of SER over a concentration range of 4-64 µg/mL at 290 nm with mean percentage recoveries 99.77±0.781. While first-derivative of the ratio spectra (1DR) is the method of choice for determination of pure SER at a maximum 300 nm and at a trough 304 nm, with mean percentage recoveries 99.98±0.720 and 100.46±0.640, respectively. The third developed HPLC method used a RP-ZORBAX C18 column (5 μm particle size, 250×4.6 mm; id) with isocratic elution. The mobile phase was methanol: 0.2% formic acid aqueous solution (75:25, v:v); pH = 3.5 at the flow rate of 1.0 mL/min, with UV detection at 260 nm. The method could determine SER in the range of 0.8-40 µg/mL with a mean percentage recovery of 99.65±0.630. The developed methods were succeeded in the determination of SER in bulk powder, pharmaceutical dosage forms and in presence of its acidic degradation products. The results obtained were validated in compliance with ICH guidelines and compared statistically with each other and to those of the official method in the British Pharmacopoeia regarding both accuracy and precision.

381-386
Abdel-Zaher Abdel-Aziz Elassar
10.5155/eurjchem.6.4.387-393.1306

Tandem cycloaddition reaction of α,β-unsaturated acid chloride with amines afforded in situ N-acylated amines, which undergoes cycloaddition reaction with other molecule of acid chloride to give dihydropyran carboxamide derivatives as an unexpected product. 2-Amino benzimidazole, 2-aminobenzthiazole, 2-aminothiazole, anthranilic acid, o-pheneylenediamine, and 3-methyl-1H-pyrazol-5(4H)-one are reacted with methacryloyl chloride at 0 °C to give different derivatives of dihydropyran carboxamide. The latter compound was obtained through acylation of the organic amines followed by tandem cycloaddition reaction. In contrast acryloyl chloride afforded only N-acylated derivatives. Both products are characterized by single crystal X-ray diffraction method. Bioactivity of the newly synthesized products was studied against Gram-positive, Gram-negative bacteria and fungus.

387-393
Honnaiah Vijay Kumar, Prasanth Kumar, Javarappa Rangaswamy, Kirugunda Udayakumar Sindhu, Nagaraja Naik
10.5155/eurjchem.6.4.394-403.1297

In rummage around for a novel antimicrobial and antioxidant agent with improved potency, we designed and synthesized a series of 5H-dibenz[b,f]azepine based pyrazole sulphonamides (20-40) by expedient five steps route. All compounds were characterized by physico-chemical and spectroscopic techniques. In order to probe the antimicrobial and antioxidant activities, the newly synthesized compounds were assayed for their in vitro activities. Among the compounds of the particular interest, compounds 38 and 39 emerged as outperformed antimicrobial agents than standard streptomycin and fluconazole. Molecular docking studies of compound 38 and 39 into S. aureus tyrosyl-tRNA synthetase active site was performed, and the tight fitting of the compounds in the active site and the associated high binding energy might be the reason for their antimicrobial activity. On the other hand, compounds 28-30 were found to exert positive efficacy towards antioxidant activity comparable to butylated hydroxy anisole.

394-403
Jabbar Saleh Hadi
10.5155/eurjchem.6.4.404-409.1299

A new series of Schiff bases were synthesized by the condensation of sulfaproxylene with various aldehydes in ethanol. The structures of Schiff bases were characterized by using elemental analysis, IR, 1H NMR, 13C NMR and Mass spectrometry techniques. Thermal stability of the prepared compounds was investigated using TG and DTG. The kinetic and thermodynamic parameters such as activation energy (E), enthalpy of activation (ΔH), entropy of activation (ΔS), and Gibbs free energy change of the decomposition (ΔG) were evaluated following Coats-Redfern method. In addition, the compounds were studied for their fluorescence properties, where compound 1 yielded the strongest intensity in 1×10-4 M DMSO solution.

404-409
Santosh Jadhav, Mahesh Shioorkar, Omprakash Chavan, Aniket Sarkate, Devanand Shinde, Rajendra Pardeshi
10.5155/eurjchem.6.4.410-416.1312

An efficient and environmentally benign method has been developed for the synthesis of 5-arylidine-2-(methylthio)-thiazolones derivatives using Alum [KAl(SO4)2·12H2O] catalyst and triethyl amine in water under microwave irradiation. This green transformation generated one C-S and one C-C bond, condensation and S-methylation. Notable advantages for the present protocol include, short reaction time, cleaner reaction profile and easy isolation of product by microwave irradiation technique using green catalyst and solvent.

410-416
Muhammad Islam, Zahid Shafiq, Mazhar Hussain, Hafiz Badaruddin Ahmad, Muhammad Ajaz Hussain
10.5155/eurjchem.6.4.417-421.1310

Some novel imine derivatives (1-14) of a broad spectrum antibiotic amoxicillin were prepared by condensation with different carbonyl compounds. The amoxicillin imine derivatives were characterized using elemental analysis and spectroscopic techniques such as FT-IR and 1H NMR. The prepared imine derivatives were evaluated for antimicrobial activities against some pathogens using disc diffusion method. The results of present studies demonstrate enhanced antimicrobial activity of the novel imine derivatives of amoxicillin as compared to the parent drug.

417-421
Amira Mohamed Kessiba, Maha Abdel Monen Hegazy, Mohamed Mohamed Abdelkawy, Ahmed Emad El Gendy
10.5155/eurjchem.6.4.422-429.1313

Two stability-indicating methods were developed and validated for the quantitative determination of acemetacin (ACM) in presence of its degradation products and impurities. The first method was based on separation of ACM from its degradation products and impurities by RP-HPLC on Inertsil C8 column (150 × 4.6 mm i.d) using a mobile phase composed of 0.02 M phosphate buffer: methanol (35:65, v:v, pH = 6.5). The flow rate was adjusted at 1 mL/min and quantification was achieved with UV detection at 245 nm using meloxicam as internal standard. The second method was based on multivariate spectrophotometric analysis using partial least square regression model. The drug was subjected to acid, base, oxidative and thermal stress conditions and the degradation products were identified. The developed methods have the requisite accuracy, selectivity, sensitivity and precision to assay ACM in presence of its degradation products and impurities either in bulk powder or in pharmaceutical dosage form. The results obtained for the analysis of ACM in its pure form by the proposed methods were statistically compared to those obtained by applying a reported HPLC method. The statistical comparison showed that there is no significant difference between the proposed methods and the reported one with respect to accuracy and precision.

422-429
Lee Jonathan Silverberg, Kurt Andrew Kistler, Kyle Brobst, Hemant Prabhakar Yennawar, Anthony Lagalante, Gang He, Khalid Ali, Ashbyilyin Blatt, Shalay Foster, Dennis Grossman, Stefan Hegel, Michael Minehan, Dana Valinsky, James Gabriel Yeasted
10.5155/eurjchem.6.4.430-443.1307

The reactions of vinylcyclopropane (+)-2-carene (1) and vinylcyclobutanes (-)-β-pinene (7),  (-)-α-pinene (11), and (-)-nopol (12) with electrophilic halogens in the presence of oxygen and nitrogen nucleophiles in various solvents have been investigated. The halonium ion intermediates that were presumably formed were very reactive and led to opening of the conjugated cyclopropane or cyclobutane. Reactions of chloramine-T trihydrate with compound 1 in acetonitrile gave amidine 13 and diazepine 14. Reactions of chloramine-T trihydrate with pinenes in methylene chloride gave allylic tosylamines 22, 16B and 24. Mechanisms to explain the observations are proposed and supported by ab initio and Density Functional Theory calculations on the carenes and pinenes in this report and their bromonium ion intermediates. For comparisons, the relative extent of conjugation with the bromonium ion moiety of these, as well as select cyclohexene and cyclohexadiene systems and their corresponding bromonium ions, were optimized at the B3LYP/cc-pVDZ level of theory, and then these geometries were analyzed using the absolute hardness index at the Hartree-Fock/aug-cc-pVDZ and B3LYP/aug-cc-pVDZ levels of theory. Additionally, Natural Population Analysis charges were calculated for these systems using Møller-Plessett Second-Order Perturbation Theory electron densities and the aug-cc-pVDZ basis set. Combining the results of these theoretical methods with analysis of structural details of their optimized geometries gives much electronic structure insight into the extent of conjugation of bromonium ions of the carenes and pinenes reported here, and places them in relative context of more traditional conjugated and non-conjugated bromonium ion systems. In particular, bromonium ions of compounds 1, 7, and 11 display structural distortions, charge delocalizations and hardness values comparable with those of traditional conjugated cyclohexadienes, with possible reasons for subtle differences presented.

430-443
Mahmoud Ali Abdelaziz Mahmoud
10.5155/eurjchem.6.4.444-450.1316

A series of new thiophene derivatives (3a,b) have been prepared by the reaction of acetylacetone with either cyanoacetanilide or 2-cyano-N-(p-tolyl)acetamide and elemental sulfur in the presence of triethylamine as basic catalyst. The two synthesized compounds were used to further synthesize new thiophene derivatives. The structures of all the newly synthesized products have been established on the basis of analytical and spectral data. The antitumor activity of the newly thiophene derivatives was evaluated against six human cancer cell lines, namely gastric cancer (NUGC), colon cancer (DLD1), liver cancer (HA22T and HEPG2), nasopharyngeal carcinoma (HONE1), breast cancer (MCF) and normal fibroblast cells (WI38).

444-450
Mouayed Hussein, Teoh Siang Guan
10.5155/eurjchem.6.4.451-460.1318

Five new thiosemicarbazone compounds derived from N(4)-methylthiosemicarbazide and 5-bromo-2-hydroxybenzaldehyde (1), 2,4-dihydroxybenzaldehyde (2), 3-ethoxy-2-hydroxy benzaldehyde (3), 3-tert-butyl-2-hydroxybenzaldehyde (4), and 2-acetylpyridine (5) have been synthesized. The molecular structures of the prepared compounds were identified using by single crystal X-ray crystallography. The binding properties of the compounds with calf thymus DNA were analyzed by UV, fluorescence titration, and viscosity measurements. The cytotoxic properties of the compounds were tested against human colorectal cell lines (HCT 116). The compounds showed greater pronounced activity than the standard reference drug 5-fluorouracil (IC50 = 7.3 μM). The results showed that the activity strength of these compounds depends on the lipophilic properties that provided by the terminal N(4)-substituent and aromatic ring-substituent, as well as the planarity that provided by the geometrical and conformational structures of the compounds.

451-460
Monther Faisal Mahdi, Ayad Mohammed Rasheed Raauf, Noor Muneer Mohammed
10.5155/eurjchem.6.4.461-467.1321

A series of six pyrazoline ring derivatives as a pharmacophore were incorporated to the naproxen; to increase its size were synthesized and preliminarly evaluated as anti-inflammatory agents with expected selectivity toward COX-2 enzyme. In vivo acute anti-inflammatory effects of the final compounds (5a-f) were evaluated in rats using egg-white induced edema model of inflammation. The tested compounds and the reference drug (naproxen) produced significant reduction of paw edema with respect to the effect of control group (propylene glycol 50%, v:v). However, compound 5d and 5e show comparable effect to naproxen at all experimental time while compounds 5a, 5b and 5c produced significantly lower inhibitory effect than naproxen at time 120-240 minutes. Furthermore, compound 5f exert significantly higher paw edema reduction than naproxen at 60-240 min. Also the antibacterial activities of the final compounds were evaluated by Well Diffusion Method. All tested compounds exert significant antibacterial activity against tested Gram positive and Gram negative bacteria in comparison to dimethyl sulfoxide as control group. In comparison the antibacterial results among the tested compound 5e may regard the best one and compound 5c the lower one.

461-467
Fathalla Belal, Mahmoud Ahmed Omar, Sayed Derayea, Sahar Zayed, Mohamed Abdelkhalek Hammad, Safaa Fathy Saleh
10.5155/eurjchem.6.4.468-474.1322

A simple, rapid, sensitive and eco-friendly liquid chromatographic method was developed and validated for the simultaneous determination of paracetamol (PAR), caffeine (CAF) and codeine (COD). The separation was performed on cyano column using a micellar mobile phase consists of 140 mM sodium dodecyl sulfate, 25 mM phosphate buffer and 10% acetonitrile at pH = 3. The analysis was performed at a flow rate of 1 mL/min and a column temperature of 30 °C under direct UV detection at 210 nm. Total analysis time was below 6 min. Baclofen (BCF) was used as an internal standard. The validation was performed according to the ICH guidelines. The proposed method was linear over the ranges of 0.2-100.0, 0.02-12.0 and 0.2-12.0 µg/mL for PAR, CAF and COD, respectively. The limits of detection were 0.031, 0.007 and 0.054 µg/mL and limits of quantification 0.103, 0.02 and 0.164 µg/mL for PAR, CAF and COD, respectively. The results show that the procedure is suitable for the routine analysis of drugs in tablet dosage forms. The method was further extended to the determination of the studied drugs in spiked human plasma with mean percentage recoveries of 99.61±0.530, 99.28±0.523 and 99.52±0.385 for PAR, CAF and COD, respectively.

468-474
Nada Sayed Abdelwahab, Maha Mohammed Abdelrahman, Fathy Mahmoud Salama, Amal Badawy Ahmed
10.5155/eurjchem.6.4.475-481.1324

Three accurate, sensitive and time saving spectrophotometric methods have been developed and validated for determination of mixture of dimenhydrinate (DMH) and cinnarizine (CIN) in presence of cinnarizine impurity (1-(diphenylmethyl)piperazine) (IMP). In method A; dimenhydrinate was determined by measuring 1D amplitudes at 292.0 nm while cinnarizine and its impurity were determined by 1DD method at 256.2 and 219.6 nm, respectively, using standard spectrum of 20 µg/mL of dimenhydrinate as a divisor. Method B depends on dividing spectrum of ternary mixture by standard spectrum of 20 µg/mL of dimenhydrinate and then cinnarizine and its impurity were determined in the obtained ratio spectrum by ratio difference method using the difference between 219.0 and 237.2 nm and between 230.0 and 264.0 nm, respectively. On the other hand dimenhydrinate could be determined by dividing spectrum of ternary mixture by standard spectrum of 20 µg/mL of cinnarizine and then it were determined at the obtained ratio spectrum by ratio difference method using the difference between 216.8 and 232.8 nm. Method C is the mean cantering of ratio spectra method (MCR) where the amplitudes at 234.8, 240.0 and 233.6 nm in the second mean centering ratio spectra were used for determination of dimenhydrinate, cinnarizine and its impurity, respectively. The developed methods were validated according to ICH guidelines regarding good accuracy and precision, and they were successfully applied to pharmaceutical formulation and laboratory prepared mixtures. The results were statistically compared with those obtained by reported method and no significant difference was found.

475-481
Suresh Seeka, Sirassu Narsimha, Kumaraswamy Battula, Althaf Hussain Shaikh, Savitha Jyostna Tangeda, Vasudeva Reddy Nagavelli
10.5155/eurjchem.6.4.482-487.1325

In view of pharmacological importance of benzimidazole and 1,2,3-triazole nuclei, we made an effort to synthesize the bi-functional mimic 1,2,3-triazolyl-benzimidazoles through the copper catalyzed azide-alkyne 1,3-dipolar cycloaddition reaction in ionic liquids. The synthesized compounds were characterized by NMR, IR and Mass spectral analysis. The synthesized compounds were screened for antimicrobial and antioxidant activities. A good number of the compounds found to possess potent antioxidant and antimicrobial activities.

482-487
Jehan Abd Elrazek Hasanen, Dalia Radwan Abd Elhafez, Ahmed Mohamed Rashad, Waleed Elazab, Ahmed Hussein Fathy
10.5155/eurjchem.6.4.488-492.1340

H-Mordenite and platinum supported H-mordenite were prepared and tested to remove phenol from aqueous solutions. The supported mordenite was prepared using wet impregnation method. The physicochemical properties of these prepared samples were characterized by several techniques such as SEM, HR-TEM, X-ray diffraction and N2 adsorption. The effects of temperature, pH, phenol concentration, catalyst amount and UV at 254 nm were studied to obtain the optimum conditions at which best removal occurs. It was seen that the removal using H-mordenite is close to the supported H-mordenite.

488-492