Ultrasound promoted one pot synthesis of novel fluorescent triazolyl spirocyclic oxindoles using DBU based task specific ionic liquids and their antimicrobial activity.

Spirocyclic oxindoles and triazolyl derivatives posses remarkable biological activities. In present work, we have described an efficient one pot four-component domino reaction of 1-(prop-2-ynyl)indoline-2,3-dione, cyclic 1,3-diketones, malononitrile and various aryl azides in DBU based ionic liquids [DBU-H]OAc and [DBU-Bu]OH under ultrasonic irradiation for the construction of heterocycles, comprising spiro-oxindole, 2-amino-4H-pyran, and 1,2,3-triazoles substructures. The antimicrobial activity of all compounds has been investigated against six microbial strains. All compounds showed good antimicrobial activity. All newly synthesized compounds exhibit fluorescence in methanol with large stoke shift.

Synthesis and Antimicrobial Activity of Some New 2-(3-(4-Aryl)-1-phenyl-1H-pyrazol-4-yl) Chroman-4-ones.

Seven new 2-(3-(4-aryl)-1-phenyl-1H-pyrazol-4-yl) chroman-4-ones (4a-4g) have been synthesized by cyclization of 2-hydroxychalcone analogues of pyrazole 3a-3g using conc. HCl in acetic acid. The structures of the compounds 4a-4g were established by the combined use of (1)HNMR, IR and mass spectra. All the seven compounds were tested in vitro for their antibacterial activity against two Gram positive bacteria namely Staphylococcus aureus and Bacillus subtilis and two Gram negative bacteria Escherichia coli and Pseudomonas aeruginosa. The compounds 4b, 4c, 4e, 4f, 4g have displayed good antibacterial activity when compared with commercially available antibiotic, ciprofloxacin. These compounds also were screened for their antifungal activity against two ear pathogenic fungi, namely Aspergillus Niger and A. flavus. The compounds 4a, 4c, 4d, 4g exhibited good antifungal activity when compared with commercially available antifungal, fluconazole.

Mechanism of platelet factor 4 (PF4) deficiency with RUNX1 haplodeficiency: RUNX1 is a transcriptional regulator of PF4.

BACKGROUND: Platelet factor 4 (PF4) is an abundant protein stored in platelet α-granules. Several patients have been described with platelet PF4 deficiency, including the gray platelet syndrome, characterized by a deficiency of α-granule proteins. Defective granule formation and protein targeting are considered to be the predominant mechanisms. We have reported on a patient with thrombocytopenia and impaired platelet aggregation, secretion, and protein phosphorylation, associated with a mutation in the transcription factor RUNX1. Platelet expression profiling showed decreased transcript expression of PF4 and its non-allelic variant PF4V1. OBJECTIVES: To understand the mechanism leading to PF4 deficiency associated with RUNX1 haplodeficiency, we addressed the hypothesis that PF4 is a transcriptional target of RUNX1. METHODS/RESULTS: Chromatin immunoprecipitation and gel-shift assays with phorbol 12-myristate 13-acetate-treated human erythroleukemia (HEL) cells revealed RUNX1 binding to RUNX1 consensus sites at -1774/-1769 and -157/-152 on the PF4 promoter. In luciferase reporter studies in HEL cells, mutation of each site markedly reduced activity. PF4 promoter activity and PF4 protein level were decreased by small interfering RNA RUNX1 knockdown and increased by RUNX1 overexpression. CONCLUSIONS: Our results provide the first evidence that PF4 is regulated by RUNX1 and that impaired transcriptional regulation leads to the PF4 deficiency associated with RUNX1 haplodeficiency. Because our patient had decreased platelet albumin and IgG (not synthesized by megakaryocytes) levels, we postulate additional defects in RUNX1-regulated genes involved in vesicular trafficking. These studies advance our understanding of the mechanisms in α-granule deficiency.

Hypervalent iodine(III) mediated synthesis of novel unsymmetrical 2,5-disubstituted 1,3,4-oxadiazoles as antibacterial and antifungal agents.

A series of novel 2,5-disubstituted 1,3,4-oxadiazoles 4 have been conveniently synthesized by oxidative cyclization of pyrazolylaldehyde N-acylhydrazones 3 promoted by iodobenzene diacetate under mild conditions (11 examples, up to 92% isolated yields). All the eleven compounds were tested in vitro for their antibacterial activity against gram-positive bacteria namely, Staphylococcus aureus, Bacillus subtilis and two gram-negative bacteria namely, Escherichia coli and Pseudomonas aeruginosa. All the synthesized compounds were also tested for their inhibitory action against two strains of fungus.

Template synthesis, spectroscopic, antibacterial, and antifungal studies of trivalent transition metal ion macrocyclic complexes.

A novel series of complexes of the type [M(C(36)H(22)N(6))X]X(2), where M = Cr(III), Mn(III), Fe(III); X = Cl(-), NO(3)(-), CH(3)COO(-); and (C(36)H(22)N(6)) corresponds to the tetradentate macrocyclic ligand, have been synthesized by condensation of 1,8-diaminonaphthalene and isatin in the presence of trivalent metal salts in methanolic medium. The complexes have been characterized by elemental analysis, conductance and magnetic measurements, and UV/Vis, IR, and mass spectroscopy. On the basis of these studies, a five coordinate square pyramidal geometry for all of these complexes is proposed. All synthesized macrocyclic complexes have been tested for in vitro antimicrobial activities against some pathogenic bacterial strains, viz. Staphylococcus aureus, Bacillus subtilis (Gram-positive), Escherichia coli, Pseudomonas aeruginosa (Gram-negative), and two fungal strains, viz. Aspergillus niger, Aspergillus flavus. The MICs shown by the complexes against these microbial strains have been compared with MICs shown by standard antibiotic ciprofloxacin and the antifungal drug amphotericin-B.

Macrocyclic metal complexes derived from 2,6-diaminopyridine and isatin with their antibacterial and spectroscopic studies.

Condensation reaction of 2,6-diaminopyridine with isatin in the presence of divalent metal ions results in the formation of the macrocyclic complexes of the type [M(C(26)H(16)N(8))X(2)], where M=Co(II), Ni(II), Cu(II), Zn(II), Cd(II) and X=Cl(-), NO(3)(-), CH(3)COO(-). The complexes have been characterized with the aid of elemental analyses, conductance measurements, electronic, NMR, infrared and EPR spectral studies. The lower values of molar conductance indicate them to be non-electrolytes. On the basis of these studies, a six coordinate distorted octahedral geometry in which four nitrogen atoms are suitably placed for coordination towards metal ion, has been proposed for all the complexes. The complexes were tested for their in vitro antibacterial activity. Some of the complexes showed good antibacterial activities against some selected bacterial strains.

Fungal infection of the ear: a common problem in the north eastern part of Haryana.

OBJECTIVE: The aim of this study was to determine the prevalence of fungal agents, sex distribution and predisposing factors involved in otomycosis. METHODS: Samples from the 118 clinically suspected patients of otomycosis were collected between January 2008 and February 2009, with an age group of 6 and 75 years. Mycological examination of all the samples was done to isolate the fungal agents involved in otomycosis. RESULTS: Mycological examination has revealed the confirmation of fungal otomycosis in 78% of the suspected patients. Pruritus has been found as the most common symptom. The major predisposing factors responsible for the otomycosis have been found as the wearing of traditional customary clothes followed by itching on other body parts and swimming. It has been found to be more prevalent in females than males in the age group of 31-40 years, higher incidence occurring in the rainy season. The fungi involved in otomycosis belonged to Aspergillus niger, A. flavus, A. fumigatus, A. luchuensis, A. terreus, Candida albicans and Penicillium sp. Of these, A. niger followed by A. flavus were the dominant fungi. Aspergillus luchuensis as the cause of otomycosis has been reported for the first time. CONCLUSION: Finally we can say higher incidence of otomycosis may be due to high degree of humidity, warm and dusty environment. So, keeping in view the high prevalence of otomycosis in India, critical diagnosis of the causative agent by employing aseptic and proper culture techniques and susceptibility testing for proper treatment of this disease is the need of the hour.

Essential Oil Composition and Antibacterial Studies of Vitex negundo Linn. Extracts.

Essential oils from fresh leaves, flowers and dried fruits of Vitex negundo were obtained by hydrodistillation. Using Soxhlet extractor five successive extracts from dried and powdered leaves were also taken. The chemical constituents of essential oil of leaves, flowers and dried fruits were analyzed by GC-FID and GC/MS techniques. Main constituents identified in leaves oil were delta-guaiene, carryophyllene epoxide and ethyl-hexadecenoate; in flowers oil - alpha-selinene, germacren-4-ol, carryophyllene epoxide and (E)-nerolidol while fruit oil showed beta-selinene, alpha-cedrene, germacrene D and hexadecanoic acid as the main constituents. beta-Caryophyllene was only the constituent identified as common to all three oils. alpha-Guaiene and guaia-3,7-diene were identified as common constituents in leaf and dried fruit oil while leaf and flower oils showed p -cymene, valencene, caryophyllene epoxide and (E)-nerolidol as common constituent. All the essential oils and successive extracts were evaluated for antibacterial potential against Staphylococcus aureus, Bacillus subtilis, Escherichia coli and Pseudomonas aeruginosa bacterial strains. Each of the essential oils and extracts were found to give promising results against B. subtilis and E. coli. Ethyl acetate and ethanol extracts showed prominent antibacterial activity against all the tested strains. Fruits and leaves oil were found to be most active against E. coli and S. aureus, respectively. Only flowers oil was found to be active against P. aeruginosa.

Evaluation of minimum inhibitory concentration of quinolones and third generation cephalosporins to Salmonella typhi isolates.

A total of 323 Salmonella typhi isolates (261 isolates obtained during 1995-99 from Ludhiana and 62 randomly selected isolates obtained between 1980-99 from Chandigarh) were analyzed for drug resistant pattern. S. typhi isolates prior to 1986 were sensitive to all the antimicrobials tested by disc diffusion method. Most common multidrug resistance pattern noticed was ACCo T i.e. resistance to ampicillin, Chloramphenicol, cotrimoxazole and tetracycline. This study has revealed that withdrawal of chloramphenicol due to high level of resistance during 1990-94, has led to re-emergence of 43-93 percent chloramphenicol sensitive mutants during 1995-99. Two S. typhi isolates in 1995 and one in 1999 from Ludhiana depicted resistance to ciprofloxacin. Susceptibility of S. typhi isolates to third generation cephalosporins ranged between 87 to 100 per cent. There was a gradual increase with time period in mean minimum inhibitory concentration (MIC) of ciprofloxacin as it increased from 0.066 ug/ml for 1980-83 S. typhi isolates to 0.13 ug/ml for the 1996-99 isolates. Similarly, cefotaxime mean MIC for 1980-83 isolate was 0.172 ug/ml which further increased up to 0.32 ug/ml for S. typhi isolates encountered between 1996-99. In contrast, mean MIC value of 0.62 ug/ml of Ceftriaxone remained unchanged irrespective of the year of isolation of S. typhi isolates.

Changing pattern of biotypes, phage types & drug resistance of Salmonella typhi in Ludhiana during 1980-1999.

BACKGROUND & OBJECTIVES: Ludhiana, an industrial city of Punjab, has a large floating population where typhoid has become endemic. A retrospective study was carried out over a period of 20 years (1980-1999) at Ludhiana on the biotyping, phage typing and drug resistance pattern of Salmonella typhi. METHODS: Of a total of 1697 S. typhi isolates obtained, phage typing and biotyping were done of only 1243 isolates. Antimicrobial susceptibility pattern of these isolates was also studied. RESULTS: Of the 1243 S. typhi isolates, 963 (77.5%) and 280 (22.5%) were of biotype I and biotype II respectively. Twenty four different S. typhi phage types were prevalent in Ludhiana in the past two decades. Between 1980 and 1989, more prevalent phage types were phage type A (35%), O (17.6%) and E1 (15.1%). During 1990-1999, there was a considerable increase in the incidence of phage type E1 (48.1%). The cumulative analysis of past two decades revealed that the incidence of phage type E1 (38.8%) was most predominant. In the past one decade (1990-1999), 412 S. typhi isolates of 13 different phage types exhibited multidrug resistance (MDR) pattern ACCoT (resistant to ampicillin, chloramphenicol, co-trimoxazole and tetracycline). High chloramphenicol resistance (74.7%) and MDR pattern ACCoT (68.2%) was shown by phage type E1 of S. typhi. INTERPRETATION & CONCLUSION: An association was observed between drug resistance and phage type pattern of S. typhi as 70 per cent isolates of S. typhi phage types E1 and O exhibited ACCoT multidrug resistant pattern. Reemergence of chloramphenicol susceptibility in the last decade emphasizes the need for regular antimicrobial surveillance to minimize the misuse of these drugs.

Immunoprophylaxis in tuberculosis.

In the Chingelput trial of immunoprophylaxis against tuberculosis, BCG vaccination did not protect against pulmonary especially bacillary tuberculosis commonly known 'adult form' of tuberculosis. The study however, did not answer the question whether BCG vaccination offers protection against 'childhood forms of tuberculosis' or not. However, notwithstanding these results, the study has generated some new ideas and has opened vast areas for future research. The results of new projects will be awaited keenly. The current situation is discussed here.