Recent molecularly imprinted polymers applications in bioanalysis.

Molecular imprinted polymers (MIPs) as extraordinary compounds with unique features have presented a wide range of applications and benefits to researchers. In particular when used as a sorbent in sample preparation methods for the analysis of biological samples and complex matrices. Its application in the extraction of medicinal species has attracted much attention and a growing interest. This review focus on articles and research that deals with the application of MIPs in the analysis of components such as biomarkers, drugs, hormones, blockers and inhibitors, especially in biological matrices. The studies based on MIP applications in bioanalysis and the deployment of MIPs in high-throughput settings and optimization of extraction methods are presented. A review of more than 200 articles and research works clearly shows that the superiority of MIP techniques lies in high accuracy, reproducibility, sensitivity, speed and cost effectiveness which make them suitable for clinical usage. Furthermore, this review present MIP-based extraction techniques and MIP-biosensors which are categorized on their classes based on common properties of target components. Extraction methods, studied sample matrices, target analytes, analytical techniques and their results for each study are described. Investigations indicate satisfactory results using MIP-based bioanalysis. According to the increasing number of studies on method development over the last decade, the use of MIPs in bioanalysis is growing and will further expand the scope of MIP applications for less studied samples and analytes.

Nanotechnology, Green Synthesis and Biological Activity Application of Zinc Oxide Nanoparticles Incorporated Argemone Mxicana Leaf Extract.

Nanomaterial is a rapidly growing area that is used to create a variety of new materials and nanotechnology applications from medical, pharmaceuticals, chemical, mechanical, electronics and several environmental industries including physical, chemical and biological nanoparticles are very important in our daily life. Nanoparticles with leaf extract from the healthy plant are important in the area of research using biosynthesis methods. Because of it's used as an environmentally ecofriendly, other than traditional physical and chemical strategies. In particular, biologically synthesized nanoparticles have become a key branch of nanotechnology. The present work presents a synthesis of zinc oxide nanoparticles using an extract from the Argemone leaf Mexicana. Biosynthetic nanoparticles are characterized by X-ray diffraction (XRD), Ultraviolet visible (UV-vis) spectroscopy analysis, a Fourier Transform Infrared Spectroscopy analysis (FTIR) and a scanning electron microcopy (SEM), X-ray analysis with dispersive energy (EDAX). XRD is used to examine the crystalline size of zinc oxide nanoparticles. The FTIR test consists in providing evidence of the presence of targeted teams. UV is used for optical properties and calculates the energy of the bandwidth slot. The scanning microscope emission reveals the morphology of the surface and the energy dispersive X-ray analysis confirms the basic composition of zinc oxide nanoparticles. It is found that zinc nanoparticles are capable of achieving high anti-fungal efficacy and therefore have a high potential antimicrobial activity of ZnO NPs, like antibacterial and high antioxidant. Zinc Oxide nanoparticles from the Argemone Mexicana leaf extract have several antimicrobial applications, such as medical specialty, cosmetics, food, biotechnology, nano medicine and drug delivery system. ZnO nanoparticles are important because they provide many practical applications in industry. The most important use of nanoparticles of ZnO would be strong antibacterial and antioxidant activity with a simple and efficient biosynthesis method may be used for future work applications.

Promising Antidiabetic and Antimicrobial Agents Based on Fused Pyrimidine Derivatives: Molecular Modeling and Biological Evaluation with Histopathological Effect.

Diabetes is the most common metabolic disorder in both developing and non-developing countries, and a well-recognized global health problem. The WHO anticipates an increase in cases from 171 million in 2000 to 366 million by 2030. In the present study, we focus on the preparation of pyrimidine derivatives as potential antidiabetic and antimicrobial agents. Thein vivoeffect on total serum glucose concentration, cholesterol and antioxidant activity was assessed in adult male albino Wister rats and compared to the reference drug glimperide. Promising results were observed for compound 5. The histopathological study confirms that compound 5 results in significant activity with liver maintenance. The antimicrobial activities were evaluated against several bacterial strains such as Salmonella typhimurium ATCC 25566, Bacillus cereus, Escherichia coli NRRN 3008, Pseudomonas aeruginosa ATCC 10145, Staphylococcus aureus ATCC 6538and fungi such as Rhizopus oligosporus, Mucor miehei and Asperillus niger. Compounds 4 and 5 showed a good inhibition of the bacterial zone compared to the reference drug cephradine. Finally, we suggest protein targets for these drugs based on computational analysis, and infer their activities from their predicted modes of binding using molecular modeling. The molecular modeling for compounds 4 and 5 resulted in improved docking scores and hydrogen bonding. The docking studies are in good agreement with the in vitro and in vivo studies.

Solid phase microextraction and related techniques for drugs in biological samples.

In drug discovery and development, the quantification of drugs in biological samples is an important task for the determination of the physiological performance of the investigated drugs. After sampling, the next step in the analytical process is sample preparation. Because of the low concentration levels of drug in plasma and the variety of the metabolites, the selected extraction technique should be virtually exhaustive. Recent developments of sample handling techniques are directed, from one side, toward automatization and online coupling of sample preparation units. The primary objective of this review is to present the recent developments in microextraction sample preparation methods for analysis of drugs in biological fluids. Microextraction techniques allow for less consumption of solvent, reagents, and packing materials, and small sample volumes can be used. In this review the use of solid phase microextraction (SPME), microextraction in packed sorbent (MEPS), and stir-bar sorbtive extraction (SBSE) in drug analysis will be discussed. In addition, the use of new sorbents such as monoliths and molecularly imprinted polymers will be presented.

Monolithic packed 96-tips set for high-throughput sample preparation: determination of cyclophosphamide and busulfan in whole blood samples by monolithic packed 96-tips and LC-MS.

A monolithic methacrylate packed 96-tips device was used for the extraction of the busulfan and cyclophosphamide in whole blood samples. Using a packed 96-tips set, a 96-well plate could be handled in about 2 min. The key aspect of the monolithic phase is that monolithic material can offer both good extraction capacity and low-back-pressure properties. The validation of the methodology showed that the accuracy values of quality-control samples were between 99 and 113% for busulfan, and between 103 and 110% for cyclophosphamide. The inter-day precision ranged from 7.0 to 12% for busulfan and from 13 to 16% for cyclophosphamide. The standard calibration curves were obtained within the concentration range 5-2000 nm for busulfan and from 10 to 5000 nm for cyclophosphamide in blood samples. The coefficients of determination were ≥0.99.

Synthesis, pharmacological activity evaluation and molecular modeling of new polynuclear heterocyclic compounds containing benzimidazole derivatives.

Novel heterocyclic compounds containing benzimidazole derivatives were synthesized from 2-(1H-benzimidazol-2-yl) acetonitrile (1) and arylhydrazononitrile derivative 2 was obtained via coupling of 1 with 4-methyl phenyldiazonium salt, which was then reacted with hydroxylamine hydrochloride to give amidooxime derivative 3. This product was cyclized into the corresponding oxadiazole derivative 4 upon reflux in acetic anhydride. Compound 4 was refluxed in DMF in the presence of triethylamine to give the corresponding 5-(1H-benzimidazol-2-yl)-2-p-tolyl-2H-1,2,3-triazol-4-amine 6. Treatment of compound 6 with ethyl chloroformate afforded 2,6-dihydro-2-(4-methylphenyl)-1,2,3-triazolo[4",5"-4',5']pyrimido[1,6-a]benzimidazole-5(4H)-one (8). 1,2-bis(2-cyanomethyl-1H-benzimidazol-1-yl)ethane-1,2-dione (10) was synthesized via the condensation reaction of 2-(1H-benzimidazol-2-yl) acetonitrile (1) and diethyloxalate. The reactivity of compound 10 towards some diamine reagents was studied. The in vitro antimicrobial activity of the synthesized compounds was investigated against several pathogenic bacterial strains such as Escherichia coli O157, Salmonella typhimurium, E. coli O119, S. paratyphi, Pseudomonas aeruginosa, Staphylococcus aureus, Listeria monocytogenes and Bacillus cereus. The results of MIC revealed that compounds 12a-c showed the most effective antimicrobial activity against tested strains. On the other hand, compounds 12a, b exhibited high activity against rotavirus Wa strain while compounds 12b, c exhibited high activity against adenovirus type 7. In silico target prediction, docking and validation of the compounds 12a-c were performed. The dialkylglycine decarboxylase bacterial enzyme was predicted as a potential bacterial target receptor using pharmacophore-based correspondence with previous leads; giving the highest normalized scores and a high correlation docking score with mean inhibition concentrations. A novel binding mechanism was predicted after docking using the MOE software and its validation.

Synthesis and biological activity of some new 1-benzyl and 1-benzoyl-3-heterocyclic indole derivatives.

Starting from 1-benzyl- (2a) and 1-benzoyl-3-bromoacetyl indoles (2b) new heterocyclic, 2-thioxoimidazolidine (4a, b), imidazolidine-2,4-dione (5a, b), pyrano(2,3-d)imida-zole (8a, b and 9a, b), 2-substituted quinoxaline (11a, b-17a, b) and triazolo(4,3-a)quinoxaline derivatives (18a, b and 19a, b) were synthesized and evaluated for their antimicrobial and anticancer activities. Antimicrobial activity screening performed with concentrations of 0.88, 0.44 and 0.22 microg mm(-2) showed that 3-(1-substituted indol-3-yl)quinoxalin-2(1H)ones (11a, b) and 2-(4-methyl piperazin-1-yl)-3-(1-substituted indol-3-yl) quinoxalines (15a, b) were the most active of all the tested compounds towards P. aeruginosa, B. cereus and S. aureus compared to the reference drugs cefotaxime and piperacillin, while 2-chloro-3-(1-substituted indol-3-yl)quinoxalines (12a, b) were the most active against C. albicans compared to the reference drug nystatin. On the other hand, 2-chloro-3-(1-benzyl indol-3-yl) quinoxaline 12a display potent efficacy against ovarian cancer xenografts in nude mice with tumor growth suppression of 100.0 +/- 0.3 %.

Tumor anti-initiating activity of some novel 3,4-dihydropyrimidinones.

Halting the tumor initiation process by targeting the inhibition of the carcinogens metabolic activators (CYP), the induction of the carcinogen detoxification enzymes (glutathione-S-transferases, GSTs), and the induction of antioxidant activity is an effective strategy. Since several dihydropyrimidine derivatives (Biginelli compounds) are therapeutically active, the present study aimed to synthesize some dihydropyrimidines with multifunctional aromatic substitutions and to investigate their effects as anti-initiating agents. Twelve compounds were synthesized and structurally elucidated. The results revealed that compound 10 was a non-cytotoxic inhibitor of cytochrome P 450 1A (Cyp1A) activity, inducer of GST activity, scavenger of OH and inhibitor of DNA fragmentation. Compounds 1 and 9 were radical scavengers of OH and inhibitors of DNA fragmentation. On the other hand, all compounds were not toxic against different tumor cells, except compounds 2, 4, and 5 possessed non specific cytotoxicity against both liver and colon carcinoma cells, while 7 possessed specific cytotoxicity only against colon carcinoma cells. Compound 1 was a non-cytotoxic inducer of GST activity, scavenger of OH and ROO, and inhibitor of DNA fragmentation. The present study proved that compounds 10 and 1 were active and safe tumor anti-initiating and multi-potent blocking agent.