An evolving role of piperazine moieties in drug design and discovery.

This article purposes to provide insights to piperazine based molecular designs that will facilitate drug discovery program in future. In our pursuit to summarize the reservoir of bioactive agents, and in line with the synthetic economy of new heterocycles, many new roles are being identified for the multiple biotargets of piperazine moieties. We mark out how series of different scaffolds provide an extensive range of various piperazine-based analogues displaying antimicrobial, antituberculosis, anticancer, antiviral and antimalarial activities.

Ion exchange chromatographic separation and isolation of oligosaccharides of intact low-molecular-weight heparin for the determination of their anticoagulant and anti-inflammatory properties.

It is well known that enoxaparin, a widely used anticoagulant and low-molecular-weight heparin containing a large number of oligosaccharides, possesses anti-inflammatory activity. Whilst enoxaparin has shown promising results in various inflammatory disorders, some of its oligosaccharides have anti-inflammatory properties and others increase the risk of bleeding due to their anticoagulant effects. The aim of this study was to develop an effective ion exchange chromatographic (IC) technique which allows the separation, isolation and, consequently, the identification of different oligosaccharides of enoxaparin with or without anticoagulant activity.

Anatomic risk factors for type-2 endoleak following EVAR: a retrospective review of preoperative CT angiography in 326 patients.

Purpose: We describe the anatomic characteristics on preoperative CT angiography (CTA) that predispose to type-2 endoleaks after endovascular aneurysm repair (EVAR) for an abdominal aortic aneurysms (AAA).

Methods: Between 1999 and 2010, 326 patients had a CTA before and after EVAR. CTAs were reviewed for maximal sac diameter, >50% circumferential luminal thrombus, and patency of the infrarenal aortic side branches, including the inferior mesenteric artery (IMA) and L2-L5 lumbar arteries.

Structural requirements for inhibitory effects of bisphenols on the activity of the sarco/endoplasmic reticulum calcium ATPase.

Bisphenols (BPs) are a class of small organic compounds with widespread industrial applications. Previous studies have identified several BPs that interfere with the activity of the ion-translocating enzyme sarco/endoplasmic reticulum calcium ATPase (SERCA). In order to define the molecular determinants of BP-mediated SERCA inhibition, we conducted enzyme activity assays with rabbit SERCA to determine the inhibitory potencies of 27 commercially available BPs, which were the basis for structure-activity relationships.

Copper(II) triflate promoted multicomponent catalytic clubbing of piperazinyl-thiazoloquinolines and thiazolocoumarins as antimicrobials.

Step economical, multicomponent construction of two series based on quinoline and coumarin ring systems was carried out. Annulation towards the 2-piperazinylthiazole system was established in satisfactory yields, using copper(II) triflate. These multicomponent reaction products were examined for their potential inhibitory effect against two Gram-positive bacteria (Staphylococcus aureus and Bacillus cereus), three Gram-negative bacteria (Escherichia coli, Pseudomonas aeruginosa, and Klebsiella pneumoniae) and two fungal species (Aspergillus niger and Candida albicans).

Chlamydia induces anchorage independence in 3T3 cells and detrimental cytological defects in an infection model.

Chlamydia are gram negative, obligate intracellular bacterial organisms with different species causing a multitude of infections in both humans and animals. Chlamydia trachomatis is the causative agent of the sexually transmitted infection (STI) Chlamydia, the most commonly acquired bacterial STI in the United States. Chlamydial infections have also been epidemiologically linked to cervical cancer in women co-infected with the human papillomavirus (HPV).

Microwave-assisted synthesis of coumarin based 1,3,5-triazinyl piperazines and piperidines and their antimicrobial activities.

A series of 1,3,5-triazine derivatives that contain aniline, 4-hydroxycoumarin and 7-hydroxy-4-methylcoumarin and different piperazines and piperidines as substituents on the carbon atoms of the triazine ring has been synthesized by a simple and efficient synthetic protocol. Comparative studies were performed on above compounds, which were synthesized with conventional and microwave heating method. The microwave method was observed to be more beneficial as it provides an increase of yield and 90-95% reduction time.

Effects of filtration on the presence of particulate and oxycodone content of injections prepared from crushed OxyContin® tablets.

It is common for injecting drug users (IDU) to prepare injections by crushing tablets which are not designed for parental administration. The injection of insoluble tablet excipients can lead to serious local and systemic medical complications. The aim of the study was to investigate the effectiveness of various types of filters in removing harmful insoluble particles from the injections prepared using crushed oxycodone tablets.

New quinolinyl-1,3,4-oxadiazoles: synthesis, in vitro antibacterial, antifungal and antituberculosis studies.

In order to generate hybrid antimicrobial remedies with novel mode of action, two series of quinoline based 1,3,4-oxadiazole derivatives condensed with N-aryl/benzothiazolyl acetamides were synthesized and the MIC values of the compounds towards eight reference bacterial strains (S. aureus, B. cereus, E.

Antimicrobial, anti-TB, anticancer and anti-HIV evaluation of new s-triazine-based heterocycles.

Background: The acquirement of resistance by microorganisms to the antimicrobial arsenal is a threat to public health. A recent WHO report estimated that 1.3 million HIV-negative people and 0.

Synthesis of s-triazine-based thiazolidinones as antimicrobial agents.

A novel series of thiazolidinone derivatives, namely 4-{4-dimethylamino-6-[4-oxo-2-phenyl-5-(4-pyridin-2-yl-piperazin-1-ylmethyl)-thiazolidin-3-yl]-[1,3,5]-triazin-2-yloxy}-1-methyl-1H-quinolin-2-ones, have been synthesized from the key intermediate 4-(4-amino-6-dimethylamino-[1,3,5]-triazin-2-yloxy)-1-methyl-1H-quinolin-2-one (5). Compound 5 was condensed with various aldehydes to give Schiff base derivatives, which after cyclization gave thiazolidinones that were linked with 1-pyridin-2-yl-piperazine to obtain the target compounds. The newly synthesized compounds were evaluated for their antimicrobial activity against eight bacteria (Staphylococcus aureus, Bacillus cereus, Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae, Salmonella typhi, Proteus vulgaris, Shigella flexneri) and four fungi (Aspergillus niger, Candida albicans, Aspergillus fumigatus, Aspergillus clavatus).

Microwave assisted synthesis and determination of in-vitro antimicrobial efficacy of well characterized s-triazinyl piperazines and piperidines.

An easy and convenient microwave-assisted synthesis of a library of s-triazinyl piperazines and piperidines, which, in addition to 4-aminobenzonitrile contain 8-hydroxyquinoline is described. The newly synthesized analogues were then subjected to determine their efficacy against some human pathogenic bacterial and fungal strains as 3 Gram negative bacteria (K. pneumoniae, S.

Synthesis of benzimidazolyl-1,3,4-oxadiazol-2ylthio-N-phenyl (benzothiazolyl) acetamides as antibacterial, antifungal and antituberculosis agents.

To affiliate multiple bioactivities in a compact heteronuclei, two series of benzimidazole based 1,3,4-oxadiazoles were synthesized and assessed in vitro for their efficacy as antimicrobial agents against eight bacteria (Staphylococcus aureus, Bacillus cereus, Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae, Salmonella typhi, Proteus vulgaris, Shigella flexneri), four fungi (Aspergillus niger, Aspergillus fumigatus, Aspergillus clavatus, Candida albicans) and Mycobacterium tuberculosis H37Rv and best results were observed amongst the N-benzothiazolyl aetamide series. The lipophilicity (LogP) influence on the biological profile (MICs) of the prepared products was also discussed. Upon biological screening, it was observed that the majority of the compounds were found to possess a significant broad spectrum antimicrobial (3.

The effect of total hip/knee replacement surgery and prophylactic dabigatran on thrombin generation and coagulation parameters.

Introduction: Total hip/knee replacement surgery (THR/TKR respectively) is associated with an increased risk of venous thromboembolism. Dabigatran is recommended as a thromboprophylactic agent post orthopaedic surgery. The aim of this study was to assess the post-operative (Day-1 and Day-2) effect of prophylactic Dabigatran on: the thrombin generation (TG) assay; prothrombin fragment 1.

Anti-hypersensitivity mechanism of action for a dentifrice containing 0.3% triclosan, 2.0% PVM/MA copolymer, 0.243% NaF and specially-designed silica.

Purpose: To evaluate the laboratory dentin occlusion efficacy and effects on dentin permeability of a new multi-benefit dentifrice in order to gain insight into the mechanism of action of a novel technology for dentin hypersensitivity relief based on a specially-designed silica and copolymer system.

Methods: Acid-etched human dentin was evaluated with confocal laser scanning microscopy (CLSM) and scanning electron microscopy (SEM) after treatment with one of the following: (1) a dentifrice containing 0.3% triclosan, 2.

Synthesis and Antimycobacterial Activity of Various 1-(8-Quinolinyloxy)-3-piperazinyl(piperidinyl)-5-(4-cyano-3-trifluoromethylphenylamino)-s-triazines.

This study presents the synthesis of novel 1-(8-quinolinyloxy)-3-piperazinyl(piperidinyl)-5-(4-cyano-3-trifluoromethylphenyl amino)-s-triazines. The synthetic route to final piperazinyl s-triazines consists of two nucleophilic substitution reactions of 4-amino-2-trifluoromethylbenzonitrile and 8-hydroxyquinoline with 2,4,6-trichloro-1,3,5-triazine resulting in 2,4-disubstituted-6-chloro-1,3,5-triazine derivatives to introduce the piperazinyl or piperidinyl functionality. The structures of the compounds were elucidated with the aid of IR, 1H NMR, 19F NMR, mass spectroscopy and elemental analysis.

Transfusion drains versus suction drains in total knee replacement: meta-analysis.

Purpose: The use of autologous blood transfusion drains in orthopaedic surgery has been the subject of debate for several years. The aim of this meta-analysis was to review the use of autologous blood transfusion drains in total knee replacement.

Methods: The primary outcomes were as follows: the number of patients requiring homologous blood transfusion, pre-operative haemoglobin and post-operative haemoglobin days 5-7.

Fluorinated s-triazinyl piperazines as antimicrobial agents.

A series of 1,3,5-triazine derivatives that contain 4-amino-2-trifluoromethyl-benzonitrile, 8-hydroxyquinoline, and different piperazines as substituents at the carbon atoms of the triazine ring have been synthesized by a simple and efficient synthetic protocol. The chemical structures of the compounds were elucidated with the aid of IR, 1H NMR and 13C NMR spectroscopy, and elemental analysis. The antimicrobial activity of the compounds was tested against seven bacteria (Staphylococcus aureus MTCC 96, Bacillus cereus MTCC 619, Escherichia coli MTCC 739, Pseudomonas aeruginosa MTCC 741, Klebsiella pneumoniae MTCC 109, Salmonella typhi MTCC 733, Proteus vulgaris MTCC 1771) and four fungi (Aspergillus niger MTCC 282, Aspergillus fumigatus MTCC 343, Aspergillus clavatus MTCC 1323, Candida albicans MTCC 183).

Intracranial internal carotid aneurysm causing diplopia.

Internal carotid intracranial aneurysms are a relatively rare form of intracranial aneurysm that presents with diplopia, retro-orbital pain and unilateral headaches. The symptoms are progressive and the diagnosis should be considered in a patient presenting with these complaints. Underlying hypertension and advanced age are specific risk factors.

Synthesis and studies of novel 2-(4-cyano-3-trifluoromethylphenyl amino)-4-(quinoline-4-yloxy)-6-(piperazinyl/piperidinyl)-s-triazines as potential antimicrobial, antimycobacterial and anticancer agents.

A series of novel s-triazine analogs were synthesized and characterized by IR, (1)H NMR, (13)C NMR, (19)F NMR spectroscopy and elemental analysis. Preliminary screening of target compounds against eight bacteria (Staphylococcus aureus, Bacillus cereus, Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae, Salmonella typhi, Proteus vulgaris, Shigella flexneria), four fungi (Aspergillus niger, Aspergillus fumigatus, Aspergillus clavatus, Candida albicans) and Mycobacterium tuberculosis H37Rv indicated that 5d, 5h, 5n, 5p, 5q, 5r, 5s, 5t and 5u were the most active compounds among twenty one studied. Thus, they were further subjected to in vitro biological evaluation against human prostate cancer cell line (DU-145) and the results indicate that two compounds 5n and 5s were markedly active.

A new class of 2-(4-cyanophenyl amino)-4-(6-bromo-4-quinolinyloxy)-6-piperazinyl (piperidinyl)-1,3,5-triazine analogues with antimicrobial/antimycobacterial activity.

This study presents the synthesis and in vitro pharmacological evaluations of novel 2-(4-cyanophenyl amino)-4-(6-bromo-4-quinolinyloxy)-6-piperazinyl (piperidinyl)-1,3,5-triazines. The title compounds were assayed for their in vitro antimicrobial activity against eight bacteria (Staphylococcus aureus, Bacillus cereus, Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae, Salmonella typhi, Proteus vulgaris, Shigella flexneria) and four fungi (Aspergillus niger, Aspergillus fumigatus, Aspergillus clavatus, Candida albicans) using paper disc diffusion and agar streak dilution method as well as against Mycobacterium tuberculosis H37Rv strain using BACTEC MGIT and Lowenstein-Jensen MIC method. The bioassay results indicate that nine compounds namely 5d, 5h, 5n, 5p, 5q, 5r, 5s, 5t and 5u could be considered as possible potential agents with dual antimicrobial and antimycobacterial activities.

Chlamydia trachomatis infection causes mitotic spindle pole defects independently from its effects on centrosome amplification.

Chlamydiae are Gram negative, obligate intracellular bacteria, and Chlamydia trachomatis is the etiologic agent of the most commonly reported sexually transmitted disease in the United States. Chlamydiae undergo a biphasic life cycle that takes place inside a parasitophorous vacuole termed an inclusion. Chlamydial infections have been epidemiologically linked to cervical cancer in patients previously infected by human papillomavirus (HPV).

Horizontal cleavage tear of discoid medial meniscus diagnosed on MRI and treated with arthroscopic partial resection.

Purpose: To provided an evidence-based summarisation of the discoid medial meniscus in conjunction with a case report describing a novel management approach which includes MRI-assisted pre-operative planning and a limited meniscal resection.

Methods: Case report and structured literature review of Medline referenced articles from 1941 to 2011.

Results: Forty-one papers describing 61 patients and 82 discoid medial menisci were identified.

Bearing couples in total hip arthroplasty.

Total hip arthroplasty is a well-established treatment for arthritis of the hip. The choice of bearing couple used for articulation should be tailored to the patient. This article reviews the history of different bearing surfaces, and outlines the advantages and disadvantages that may influence their use.