Synthesis, Structural Analysis and Screening of Some Novel 5-Substituted Aryl/Aralkyl-1,3,4-Oxadiazol-2-Yl 4-(Morpholin-4-Ylsulfonyl)Benzyl Sulfides as Potential Antibacterial Agents

A series of new 5-substituted aryl/aralkyl-1,3,4-oxadiazol-2-yl 4-(morpholin-4-ylsulfonyl)benzyl sulfides 6a-k were synthesized by converting multifarious aryl/aralkyl organic acids 1a-k successively into corresponding esters 2a-k, hydrazides 3a-k and 5-substituted aryl/aralkyl-1,3,4-oxadiazole-2-thiols 4a-k. Finally, the target compounds, 6a-k were prepared by stirring 5-substituted-1,3,4-oxadiazole-2-thiols with 4-(4-(bromomethyl)phenylsulfonyl) morpholine (5) in the presence of N,N-dimethylformamide (DMF) and sodium hydride (NaH). The structures of the newly synthesized compounds were elucidated by spectroscopic techniques. In addition, the anti-bacterial activity of all the synthesized compounds was investigated in vitro against Gram-positive and Gram-negative bacteria by using ciprofloxacin as reference standard drug and the results showed that some of the tested compounds possessed good anti-bacterial activity

Hepatitis B virus in Pakistan: A systematic review of prevalence, risk factors, awareness status and genotypes

In Pakistan, there are estimated 7-9 million carriers of hepatitis B virus (HBV) with a carrier rate of 3-5%. This article reviews the available literature about the prevalence, risk factors, awareness status and genotypes of the HBV in Pakistan by using key words; HBV prevalence, risk factors, awareness status and genotypes in Pakistani population in PubMed, PakMediNet, Directory of Open Access Journals (DOAJ) and Google Scholar. One hundred and six different studies published from 1998 to 2010 were included in this study. Weighted mean and standard deviation were determined for each population group. The percentage of hepatitis B virus infection in general population was 4.3318% ± 1.644%, healthy blood donors (3.93% ± 1.58%), military recruits (4.276% ± 1.646%), healthcare persons (3.25% ± 1.202%), pregnant women (5.872% ± 4.984), prisoners (5.75% ± 0.212%), surgical patients (7.397% ± 2.012%), patients with cirrhosis (28.87% ± 11.90%), patients with HCC (22% ± 2.645%), patients with hepatitis (15.896% ± 14.824%), patients with liver diseases (27.54% ± 6.385%), multiple transfused patients (6.223% ± 2.121%), opthalmic patients (3.89% ± 1.004%) and users of injectable drugs (14.95% ± 10.536%). Genotype D (63.71%) is the most prevalent genotype in Pakistani population. Mass vaccination and awareness programs should be initiated on urgent basis especially in populations with HBV infection rates of more than 5%

Positional effect of phosphorylation sites 266 and 267 in the cytoplasmic domain of the E2 protein of hepatitis C virus 3a genotype: Interferon Resistance analysis via Sequence Alignment

<p>Abstract</p> <p>Background</p> <p>Interferon is well thought-out as the key defence against all infections including HCV. The only treatment for HCV infection is pegylated interferon alpha (IFN-α) but unluckily more than half of the infected individuals do not act in response to the cure and become chronic HCV carriers. The mechanism how HCV induce interferon resistance is still elusive. It is recently reported that HCV envelope protein 2 interacts with PKR which is the interferon-inducible protein kinase and which in turn blocks the activity of its target molecule called eukaryotic initiation factor elF2. Sequence analysis of Envelope protein reveals it contains a domain homologous to phosphorylation sites of PKR andthe translation initiation factor eIF2alpha. Envelope protein competes for phosphorylation with PKR. Inhibition of kinase activity of PKR is postulated as a mechanism of to interferon (IFN) resistance.</p> <p>Results</p> <p>Present study involves the insilico investigation of possible role of potential phosphorylation in envelope 2 protein of 3a genotype in interferon resistance. Envelope protein coding genes were isolated from local HCV isolates, cloned and sequenced. Phylogenetic analysis was done and tertiary structure of envelope gene was predicted. Visualization of phosphorylation in tertiary structure reveals that residue 266 and 267 of envelope gene 2 are surface exposed and their phosphorylation may compete with the phosphorylation of PKR protein and possibly involved in mediating Interferon Resistance.</p> <p>Conclusion</p> <p>A hybrid in-silico and wet laboratory approach of motif prediction, evolutionary and structural analysis has pointed out serine 266 and 267 of the HCV E2 gene as a hopeful claimant for the serine phosphorylation. Recognition of these nucleotide variations may assist to propose genotype precise therapy to avoid and resolve HCV infections.</p

Hepatitis Associated Aplastic Anemia: A review

Hepatitis-associated aplastic anemia (HAAA) is an uncommon but distinct variant of aplastic anemia in which pancytopenia appears two to three months after an acute attack of hepatitis. HAAA occurs most frequently in young male children and is lethal if leave untreated. The etiology of this syndrome is proposed to be attributed to various hepatitis and non hepatitis viruses. Several hepatitis viruses such as HAV, HBV, HCV, HDV, HEV and HGV have been associated with this set of symptoms. Viruses other than the hepatitis viruses such as parvovirus B19, Cytomegalovirus, Epstein bar virus, Transfusion Transmitted virus (TTV) and non-A-E hepatitis virus (unknown viruses) has also been documented to develop the syndrome. Considerable evidences including the clinical features, severe imbalance of the T cell immune system and effective response to immunosuppressive therapy strongly present HAAA as an immune mediated mechanism. However, no association of HAAA has been found with blood transfusions, drugs and toxins. Besides hepatitis and non hepatitis viruses and immunopathogenesis phenomenon as causative agents of the disorder, telomerase mutation, a genetic factor has also been predisposed for the development of aplastic anemia. Diagnosis includes clinical manifestations, blood profiling, viral serological markers testing, immune functioning and bone marrow hypocellularity examination. Patients presenting the features of HAAA have been mostly treated with bone marrow or hematopoietic cell transplantation from HLA matched donor, and if not available then by immunosuppressive therapy. New therapeutic approaches involve the administration of steroids especially the glucocorticoids to augment the immunosuppressive therapy response. Pancytopenia following an episode of acute hepatitis response better to hematopoietic cell transplantation than immunosuppressive therapy

Synthesis of 3-[4-(2-furoyl)-1-piperazinyl]-N- (substituted)propanamides as promising antibacterial agents with mild cytotoxicity

Purpose: To evaluate the antibacterial activity and cytotoxicity of a series of molecules with amalgamation of furoyl, piperazine and amide moieties.Methods: New derivatives, namely 3-[4-(2-furoyl)-1-piperazinyl]-N-(substituted) propanamides, were synthesized and evaluated for their antibacterial activity and toxicity to mammalian cells. The synthesis was initiated by treating different aryl/aralkyl amines (1a-u) with 3-bromopropionyl chloride (2) to obtain the solid electrophiles 3a-u, which were collected by filtration. Thereafter, the different N-aryl/aralkyl-3- bromopropionamides (3a-u) and 2-furoyl-1-piperazine (4) at equimolar ratios were allowed to react in acetonitrile and in the presence of a base, K2CO3, to form the target compounds, 5a-u. Structural elucidation was carried out using EI-MS (electron impact mass spectrometry), IR (infrared) and 1H-NMR (proton nuclear magnetic resonance). The antibacterial activity of the synthesized compounds was evaluated against various bacterial strains. Furthermore, hemolysis was determined to assess cytotoxicity using bovine red blood cells.Results: Molecules 5g, 5a, 5p, 5g and 5i were found to be potent agents against S. aureus, S. typhi, P. aeruginosa, E. coli and B. subtilis with respective minimum inhibitory concentration (MIC) values of 8.34 ± 0.55, 8.37 ± 0.12, 8.65 ± 0.57, 8.97 ± 0.12 and 9.24 ± 0.50 μM, compared to 7.80 ± 0.19, 7.45 ± 0.58, 7.14 ± 0.58, 7.16 ± 0.58 and 7.29 ± 0.90 μM for the reference standard, ciprofloxacin. The most active compounds, 5a, 5g, 5i and 5p, showed a hemolysis of 15.48, 8.03, 5.52 and 4.35 %, respectively.Conclusion: The synthesized compounds exhibit good antibacterial activity. The hemolysis data indicate that these compounds have a low toxicity level. However, in vivo studies are required to ascertain their potentials as new drug candidates.Keywords: 4-(2-Furoyl)-1-piperazine, 1H-NMR, EI-MS, Antimicrobial activity, Hemolytic activit

An investigation of mechanical properties of fly ash based geopolymer and glass fibers concrete

This paper presents an innovative approach towards the development of a green concrete. The geopolymer is an environmentally friendly construction/repairing material. In addition, glass fibers are helpful to influence the strength properties and to reduce hair line cracks and bleeding in concrete. This study is based on the use of fly ash and glass fibers as a partial replacement of cement and, subsequently, its effect on compressive strength and split tensile strength of concrete. The geopolymer is manufactured after the process of geopolymerization between class F fly ash and alkali activator fluid (sodium silicate and sodium hydroxide). In geopolymer concretes (GPC), an inorganic polymer called aluminosilicate will act as a binder, the same as conventional concrete has Portland cement (OPC)-generated C-S-H gel. The glass fibers are added in the ratios of 3%, 6%, and 10% by weight of cement. To check the effect of geopolymer and glass fibers on compressive strength and split tensile strength of concrete, concrete cubes of size 150 × 150 × 150 mm and concrete cylinders of size 150 × 300 mm with or without geopolymer and glass fibers were casted and cured for 7, 14, 21, and 28 days. The compressive strength and split tensile strength of all concrete cubes and cylinders were determined by compression testing machine. The findings of the research study revealed that concrete having geopolymer and glass fibers used as a partial replacement of cement showed lesser strength as compared to conventional concrete. Concrete having glass fibers showed reduced workability and more segregation as compared to geopolymer concrete and normal concrete. However, the concrete made either with geopolymer or glass fibers is economical as compared to conventional concrete

Effects of Host and virus related factors on Interferon-α+ribavirin and Pegylated-interferon+ribavirin treatment outcomes in Chronic Hepatitis C patients

<p>Abstract</p> <p>Background</p> <p>Current standard therapy commonly followed for chronic Hepatitis C Virus (HCV) in Pakistan is interferon alpha plus ribavirin combination therapy (IFN α/ribavirin) and pegylated interferon plus ribavirin (PegIFN/ribavirin). PegIFN/ribavirin has increased rate of sustained virological response than standard IFN α/ribavirin therapy. Objective of current study was to analyze rate of early and delayed response to antiviral treatment as well as rate of relapse response in patients following standard treatment IFN α/ribavirin and in patients following pegylated interferon treatment.</p> <p>Methods</p> <p>Baseline serum samples of 153 patients enrolled for IFN α/ribavirin and 50 patients for PegIFN/ribavirin were collected. After total RNA extraction, genotyping was and HCV RNA viral load was done. Subsequently HCV RNA viral load was estimated at 4 weeks of treatment, at 12 weeks, at 24 or 48 weeks and finally after 6 months follow up period. All the data was statistically analyzed using fisher's exact test.</p> <p>Results</p> <p>Total 86 patients out of 153 patients following conventional IFN α/ribavirin therapy completed treatment and 69% of them showed Rapid Virological Response (RVR). Whereas 50 patients following PegIFN/ribavirin treatment completed treatment and 80% of them achieved RVR. Total 64 out of 86 patients following IFN α/ribavirin therapy completed follow up period and 53.5% of them achieved Sustainded Virologcal Response (SVR). Forty-five out of total 50 patients who received PegIFN/ribavirin treatment completed 6 months follow up period and among these 70% achieved SVR. SVR rates were significantly associated with RVR (p < 0.001), age (p < 0.001) and gender (p < 0.01)</p> <p>Conclusions</p> <p>Rate of sustained virological response can be determined by factors like rapid virological response and age since they share significant association with one another. More over rate of SVR was more prominent in males than in females.</p

Synthesis, Characterization, Antibacterial, α-Glucosidase Inhibition and Hemolytic Studies on Some New N-(2,3- Dimethylphenyl)benzenesulfonamide Derivatives

Purpose: To synthesize a series of new N-(2,3-dimethylphenyl)benzenesulfonamide derivatives with pharmacological analysis.Methods: N-(2,3-Dimethylphenyl)benzenesulfonamide (3) was synthesized by the reaction between 2,3-dimethylaniline (1) and benzenesulfonyl chloride (2) in aqueous basic medium. Compound 3 was further treated with various alkyl/aralakyl halides (4a-m) to yield new compounds, 5a-m, in a weak basic aprotic polar organic medium. The proposed structures of synthesized compounds were confirmed using proton-nuclear magnetic resonance (1H-NMR), infra red spectroscopy (IR) and electron impact mass spectrometry (EIMS). The synthesized compounds were screened for in vitro antibacterial, antienzymatic and hemolytic activities using standard procedures.Results: All the synthesized compounds showed moderate to high activity against Gram-positive and Gram-negative bacterial strains. The molecules 5g and 5j exhibited good inhibition of α-glucosidase enzyme with half-maximal inhibitory concentration (IC50) of 59.53 ± 0.01 and 55.31 ± 0.01 μmoles/L, respectively, relative to acarbose with IC50 of 38.25 ± 0.12 μmoles/L. All the compounds exhibited cytotoxicity levels ranging from 27.20 ± 0.24 to 5.20 ± 0.41 %, relative to Triton X-100.Conclusion: Compound 5f is the most potent antibacterial while 5j is the best α-glucosidase inhibitor; 5e showed the least cytotoxicity.Keywords: 2,3-Dimethylaniline, Antibacterial activity, Anti-enzymatic activity, α-Glucosidase inhibitor, Hemolytic activity, Sulfonamide