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The present study describes a facile and efficient synthesis of 1-(N-arylacetamide)-4-phenyl-2-pyrazolyl-imidazole 7a–7t by reacting 1-(4-phenyl-1H-imidazol-2-yl)-1H-pyrazole (3a)/3,5-dimethyl-1-(4-phenyl-1H-imidazol-2-yl)-1H-pyrazole (3b) with 2-bromo-N-substitutedacetamide 6a–6j) in good yield. The structure of compounds 7a–7t are confirmed by various spectral techniques. All the prepared compounds are examined for in-vitro antimicrobial activities against three bacterial strains; S. aureus, B. subtilis and E. coli and two fungal strains; C. albicans and A. niger. The synthesized analogues show moderate inhibitory activity against tested bacterial strains and the compounds 7a, 7b, 7l, 7m and 7r exhibited good activity against C. albicans. Most of the compounds obey the Lipinski rule of five. The compound 7b is docked in the active site of C. albicans sterol-14α-demethylase and DNA gyrase to find the binding conformation.

Garlic, as well as several natural food ingredients such as basil, ginger, turmeric, cinnamon, clove, pepper etc., has long been traditionally used as routine anti-viral and anti-bacterial remedy. Allyl methyl sulfide (AMS) is reportedly a persistent main active metabolite component of allicin after garlic ingestion accounting for at least 90% of the allicin consumed. Several studies have reported the presence of AMS in organs such as lung, kidney etc. and body fluids such as mucous, and blood-plasma. Glycoproteins of enveloped viruses are actively involved in viral pathogenesis. N-acetylneuraminic acid (sialic acid) and N-Acetylglucosamine, are some of the vital amino acids involved in several viral infections using glycoproteins via glycosylation. Simulations studies based on First-principles density functional theory show that these amino acids attach with AMS, and the reactions are thermodynamically spontaneous (ΔG and ΔS negative are at 310.15 K as well as lower and higher temperatures). Further, phospholipid phosphatidylethanolamine (a component of some viral envelops) also attaches readily with AMS and the reaction is spontaneous. AMS molecules attachment with viral phospholipids and amino-acids involved in viral infection would denature the virus and prevent its attachment to the host cell. Communicated by Ramaswamy H. Sarma.

An efficient route for the synthesis of triazole containing triaryl-1H-imidazole (3a–3r) was achieved involving multicomponent condensation of triazole aldehydes, ammonium acetate and 1,2-dicarbonyl compounds in glacial acetic acid. The structure of newly synthesized imidazoles was established by the FTIR, HRMS and NMR spectra. All the compounds displayed considerable antimicrobial activity against fungal and bacterial strains. The triazolyl imidazole 3p was substantially potent against P. aeruginosa (0.0113 µmol/mL), A. niger (0.0113 µmol/mL) and C. albicans (0.0056 µmol/mL) wherein triazolyl imidazoles 3i was found to be more potent against B. subtilis (0.0122 µmol/mL) & A. niger (0.0121 µmol/mL); and compound 3r was also found to be more potent against S. epidermidis (0.0117 µmol/mL) & C. albicans (0.0058 µmol/mL). As a result of docking studies, the binding affinity of the compound 3o was –9.6 kcal/mol which was even more in comparison to the binding affinity of co-crystallized ligand CBN (–9.4 kcal/mol).

The present work relates to the processing of dense alumina-based composites, their microstructural characterization and study of mechanical properties. Alumina ceramic material and alumina-based c...

The present work involves an investigation to find out the best combination of process parameters for a Fe–Cr–Mo alloy with the help of Design of Experiments (DOE) tool. The Fe–Cr–Mo alloy containing 0, 0.4 and 0.8 wt.% carbon is compacted at 650 MPa pressure and sintered at 1120°C and 1200°C temperature, respectively, with 3.5 or 6°C/minute cooling rate. Quality characteristics like hardness and tensile strength are analyzed for various combinations of graphite weight %, sintering temperature, and cooling rate. The conducted experimental trials are based on the design matrix obtained from general factorial design. Significant regression models are developed from the above mentioned process parameters to predict the quality characteristics using DOE tool. The developed mathematical model during the course of research helped in investigating best combination of process parameters for powder processing. The desirability test showed its usefulness in finding out the number of optimization strategies ...

An open label, controlled clinical study was conducted in Indian infants aged 6-14 weeks to compare the immunogenicity and safety of a reconstituted pentavalent vaccine (DTwP-HBV+Hib) of Serum Institute of India Ltd (SIIL) with TritanrixHB+Hiberix vaccine of Glaxo Smithkline (GSK).Eligible infants were randomized to receive three doses of the study / comparator vaccine. The vaccines were reconstituted prior to administration, by mixing DTwP-HBV (liquid) with the Hib (lyophilized) vaccine. IgG antibody titres were assessed by ELISA at baseline and after one month following the 3-dose primary immunization schedule. Safety was evaluated after each dose. Further, safety and immunogenicity was also evaluated following a booster dose in the same cohort of children (aged between 15-24 months).Tertiary-care hospitals in India Important outcome measures: Immunogenicity and safety following a 3-dose primary vaccination series and a booster vaccination.Post-primary immunization, 100% seroprotection was noted for Diphtheria, Tetanus, Hepatitis B and PRP-Hib components in both the vaccine groups. For pertussis, response was 96.1% in SIIL and 95.4% in GSK group. The overall safety profile as well as persistence of antibodies against all vaccine components up to the time of booster immunization was comparable between the SIIL and GSK groups. A marked rise of all antibody concentrations indicated effective priming. The booster dose was safe, well tolerated with a significant increase in antibody concentrations of all the vaccine antigens in both the groups.DTwP-HBV+Hib vaccine of SIIL was found to be safe and immunogenic. This Indian vaccine compared well with the licensed vaccine and is a cost-effective alternative for incorporating into the immunization schedule of various countries so as to control worldwide Hepatitis B and Hib infections.

In view of the need for a cost effective Haemophilus influenzae type b (Hib) conjugate vaccine, a lyophilized vaccine as capsular polysaccharide (PRP) conjugated to tetanus toxoid (Sii HibPRO) was indigenously developed by Serum Institute of India Ltd., Pune (SIIL). From 2004-07, this new vaccine underwent a series of clinical studies before its licensure by National Regulatory Authority (NRA). This paper discusses the results obtained during the clinical development of this vaccine. On finding the vaccine to be safe in animal toxicity studies, a Phase I single dose study was carried out to assess the safety profile of Sii HibPRO in healthy adult male volunteers. Subsequently, in Phase III pre-licensure study, immunogenicity and safety of Sii HibPRO was assessed and compared with Hib tetanus conjugate vaccine (Act-HIB) of Aventis, France. Immunogenicity was evaluated based upon serum anti-PRP IgG antibody concentrations by ELISA at prevaccination and one month each after the second and third dose. Safety was evaluated by recording details of adverse events after each dose of the vaccine. Postvaccination after the third dose, there was 100% seroprotection (anti PRP IgG titre >or= 0.15 microg/ml) in both the groups. Long term protection (>or=1 microg/ml) was achieved in 95.2% and 98.06% infants in Sii HibPRO and Act-HIB groups, respectively. At 15 months, prior to booster dose, 30 children in each group were evaluated and all were found to be seroprotected. Post booster, all of them responded with a strong boost response. Safety of Sii HibPRO was re-established in the post marketing surveillance in which 2,739 doses were administered to 1,029 infants, in 23 cities across India.