Biomedical subjects

Rajesh Dabur

Publications and source records attributed to Rajesh Dabur.

10 recordsLinked to original sources

PubMed2005

Synthesis and antibacterial activity of substituted 1,2,3,4-tetrahydropyrazino [1,2-a] indoles.

A series of substituted 1,2,3,4-tetrahydropyrazino [1,2-a] indole derivatives have been synthesized and tested against the Gram positive and Gram negative strains of bacteria namely Staphylococcus aureus (MTCCB 737), Salmonella typhi (MTCCB 733), Pseudomonas aeruginosa (MTCCB 741), Streptomyces thermonitrificans (MTCCB 1824) and Escherichia coli (MTCCB 1652). All synthesized compounds showed mild to moderate activity. However, compounds 4d-f were found to have potent activity against pathogenic bacteria used in the study. Their MIC ranged from 3.75 to 60 microg/disc. In vitro toxicity tests demonstrated that toxicity of 4d-f was not significantly different than that of gentamycin. However, at higher concentration (1000-4000 microg/ml) difference was highly significant.

Anti-Bacterial Agents↗

PubMed2005

Microwave-assisted synthesis of antimicrobial dihydropyridines and tetrahydropyrimidin-2-ones: novel compounds against aspergillosis.

Ten 4-aryl-1,4-dihydropyridine and three 4-aryl-1,2,3,4-tetrahydropyrimidin-2-one derivatives have been synthesized and examined for their activity against pathogenic strains of Aspergillus fumigatus and Candida albicans. Although none of the three compounds belonging to pyrimidin-2-one series showed any activity against two pathogens, two of the compounds of the dihydropyridine series, that is, diethyl 4-(4-methoxyphenyl)-2,6-dimethyl-1,4-dihydropyridin-3,5-dicarboxylate and dimethyl 4-(4-methoxyphenyl)-2,6-dimethyl-1,4-dihydropyridin-3,5-dicarboxylate, exhibited significant activity against A. fumigatus in disc diffusion, microbroth dilution and percent spore germination inhibition assays. The most active diethyl dihydropyridine derivative exhibited a MIC value of 2.92 microg/disc in disc diffusion and 15.62 microg/ml in microbroth dilution assays. The MIC(90) value of the most active compound by percent germination inhibition assay was found to be 15.62 microg/ml. The diethyl dicarboxylate derivative of dihydropyridine also exhibited appreciable activity against C. albicans. The in vitro toxicity of the most active diethyl dihydropyridine derivative was evaluated using haemolytic assay, in which the compound was found to be non-toxic to human erythrocytes even at a concentration of 625 microg/ml. The standard drug amphotericin B exhibited 100% lysis of erythrocytes at a concentration almost 16 times less than the safer concentration of the most active dihydropyridine derivative.

Antifungal Agents↗

PubMed2005

Crystal structure of the restriction-modification system control element C.Bcll and mapping of its binding site.

Protection from DNA invasion is afforded by restriction-modification systems in many bacteria. The efficiency of protection depends crucially on the relative expression levels of restriction versus methytransferase genes. This regulation is provided by a controller protein, named C protein. Studies of the Bcll system in E. coli suggest that C.Bcll functions as a negative regulator for M.Bcll expression, implying that it plays a role in defense against foreign DNA during virus infection. C.Bcll binds (Kd = 14.3 nM) to a 2-fold symmetric C box DNA sequence that overlaps with the putative -35 promoter region upstream of the bcllM and bcllC genes. The C.Bcll fold comprises five alpha helices: two helices form a helix-turn-helix motif, and the remaining three helices form the extensive dimer interface. The C.Bcll-DNA model proposed suggests that DNA bending might play an important role in gene regulation, and that Glu27 and Asp31 in C.Bcll might function critically in the regulation.

Amino Acid Sequence↗

PubMed2005

A fraction from Escherichia coli with anti-Aspergillus properties.

The products of various strains of Escherichia coli (BL21, DH5alpha, HB101 and XL Blue) were investigated for antimycotic properties using pathogenic isolates of Aspergillus. Co-culture experiments revealed that E. coli strains exhibited variable activity against Aspergillus fumigatus. The lysates prepared from DH5alpha, HB101 and XL Blue strains of E. coli showed inhibitory activity against A. fumigatus in the protein concentration range of 62.50 to 250.00 microg ml(-1). The highest activity was seen in the lysate of BL21, which inhibited the growth of A. fumigatus and Aspergillus flavus completely at a concentration of 31.25 microg protein ml(-1). The MIC of BL21 lysate against Aspergillus niger was found to be 62.50 microg ml(-1). The in vitro toxicity of BL21 lysate was evaluated using a haemolytic assay. A BL21 lysate protein concentration of 1250.00 microg ml(-1) was found to be nontoxic to human erythrocytes. The standard drug amphotericin B lysed 100 % of erythrocytes at a concentration of 37.50 microg ml(-1). SDS-PAGE showed the presence of at least 15 major proteins in the lysate of BL21. Ion-exchange chromatography resolved the BL21 lysate into five fractions and fraction III was found to be endowed with anti-Aspergillus properties. The MIC of this fraction was found to be 3.90 microg ml(-1). Further work on the purification of the active molecule and its characterization is in progress.

Antifungal Agents↗

PubMed2005

In vitro antifungal activity of 2-(3,4-dimethyl-2,5-dihydro-1H-pyrrol-2-yl)-1-methylethyl pentanoate, a dihydropyrrole derivative.

A novel compound 2-(3,4-dimethyl-2,5-dihydro-1H-pyrrol-2-yl)-1-methylethyl pentanoate was isolated from the plant Datura metel L. The in vitro activity of this dihydropyrrole derivative against Aspergillus and Candida species was evaluated by using standard methods approved by the National Committee for Clinical Laboratory Standards. The compound was found to be active against all the species tested, namely Candida albicans, Candida tropicalis, Aspergillus fumigatus, Aspergillus flavus and Aspergillus niger. The MIC at which more than 90% of growth was inhibited (MIC(90)) by the compound ranged from 21.87 to 43.75 microg ml(-1) against various fungal species by microbroth dilution assay. Since the compound 2-(3,4-dimethyl-2,5-dihydro-1H-pyrrol-2-yl)-1-methylethyl pentanoate has antifungal activity it can be explored further to develop new antimycotic drugs.

Antifungal Agents↗

PubMed2005

Efficacy of 2-(3,4-dimethyl-2,5-dihydro-1h-pyrrole-2-yl)-1-methylethyl pentanoate in a murine model of invasive aspergillosis.

2-(3,4-Dimethyl-2,5-dihydro-1H-pyrrole-2-yl)-1-methylethyl pentanoate, an antifungal compound, was found to be nontoxic to RAW cells up to a concentration of 312.5 microg/ml, whereas amphotericin B was lethal to all cells at 37.5 microg/ml. The treatment of Aspergillus fumigatus-infected mice with a dose of 200.0 mg of compound/kg of body weight increased their survival rate by 60%, with a decrease in CFU in organ tissues. The protection afforded by the compound against experimental aspergillosis was found to be dose dependent.

Amphotericin B↗

PubMed2005

Construction of ordered protein arrays.

Artificially ordered protein arrays provide a facile approach to a variety of problems in biology and nanoscience. Current demonstration systems use either nucleic acid tethers or methyltransferase fusions in order to target proteins or peptides of interest to nucleic acid scaffolds. These demonstrations point to the large number of useful devices and assemblies that can be envisioned using this approach, including smart biological probes and drug delivery systems. In principle, these systems are now capable of imitating the earliest forms of prebiotic organisms and can be expected to reach the complexity of a small virus in the near future. Third-generation methyltransferase inhibitors provide an example of a smart chemotherapeutics that can be constructed with this approach. We describe the use of mechanistic enzymology, computer-aided design, and microfluidic chip-based capillary electrophoresis in assessing the final assembly and testing of designs of this type.

Deoxyribonucleases, Type II Site-Specific↗

PubMed2004

Antifungal potential of Indian medicinal plants.

Fourteen Indian plants, selected based on their use in respiratory and other disorders in traditional systems of medicine, were analyzed for their potential activity against fungi. The antifungal activity was investigated by disc diffusion, microbroth dilution and percent spore germination inhibition tests against pathogenic Aspergilli. Methanolic extracts of Solanum xanthocarpum and Datura metel inhibited the growth of Aspergillus fumigatus, A. flavus and A. niger and their in vitro MICs were found to be 1.25-2.50 mg/ml by both microbroth dilution and percent spore germination assays. In disc diffusion assay, a concentration of 0.062 mg/disc of methanol extract of D. metel showed significant activity against Aspergilli. S. xanthocarpum exhibited similar activity at 0.125 mg/disc.

Antifungal Agents↗

PubMed2003

Mobility-shift analysis with microfluidics chips.

Electrophoretic mobility shift analysis (EMSA) is a well-characterized and widely used technique for the analysis of proten-DNA interaction and the analysis of transcription factor combinatorics. Currently implemented EMSA generally involves the time-consuming use of radiolabeled DNA and polyacrylamide gel electrophoresis. We are studying the bionanoscience of self-assembling supramolecular protein-nucleic nanostructures. We have undertaken these studies because they promise to enhance our understanding of assemblies formed during prebiotic evolution, provide tools for analysis of biological processes like DNA recombination, and may lead to the development of nanoscale biosensors designed for site-specific molecular targeting. During the course of that work, we noted that EMSA of these complex structures could be effectively implemented with microfluidics chips designed for the separation of DNA fragments. In this report we compare the two techniques and demonstrate that the microfluidics system is also capable of resolving complex mixtures produced by decorating DNA recombination intermediates with mixtures of DNA binding proteins. Moreover, the microfluidics chip system improves EMSA by permitting analysis with smaller samples, avoiding the use of radiolabeling, and reducing the time involved to a matter of minutes.

Computer Simulation↗

PubMedDate not supplied

The role of glutathione in cancer.

Glutathione is an abundant natural tripeptide found within almost all cells. Glutathione is highly reactive and is often found conjugated to other molecules via its sulfhydryl moiety. It instils several vital roles within a cell including antioxidation, maintenance of the redox state, modulation of the immune response and detoxification of xenobiotics. With respect to cancer, glutathione metabolism is able to play both protective and pathogenic roles. It is crucial in the removal and detoxification of carcinogens, and alterations in this pathway, can have a profound effect on cell survival. However, by conferring resistance to a number of chemotherapeutic drugs, elevated levels of glutathione in tumour cells are able to protect such cells in bone marrow, breast, colon, larynx and lung cancers. Here we present a number of studies investigating the role of glutathione in promoting cancer, impeding chemotherapy, and the use of glutathione modulation to enhance anti-neoplastic therapy.

Anticarcinogenic Agents↗