Synthesis and mechanistic studies of diketo acids and their bioisosteres as potential antibacterial agents

A series of diketo esters and their pertinent bioisosteres were designed and synthesized as potent antibacterial agents by targeting methionine amino peptidases (MetAPs). In the biochemical assay against purified MetAPs from Streptococcus pneumoniae (SpMetAP1a), Mycobacterium tuberculosis (MtMetAP1c), Enterococcus faecalis (EfMetAP1a) and human (HsMetAP1b), compounds 3a, 4a and 5a showed more than 85% inhibition of all the tested MetAPs at 100 μM concentration. Compounds 4a and 5a also exhibited antibacterial potential with MIC values 62.5 μg/mL (S. pneumoniae), 31.25 μg/mL (E. faecalis), 62.5 μg/mL (Escherichia coli) and 62.5 μg/mL (S. pneumoniae), 62.5 μg/mL (E. coli), respectively. Moreover, 5a also significantly inhibited the growth of multidrug resistant E. coli strains at 512 μg/mL conc., while showing no cytotoxic effect towards healthy CHO cells and thus being selected. Growth kinetics study showed significant inhibition of bacterial growth when treated with different conc. of 5a. TEM analysis also displayed vital damage to bacterial cells by 5a at MIC conc. Moreover, significant inhibition of biofilm formation was observed in bacterial cells treated with MIC conc. of 5a as visualized by SEM micrographs. Interestingly, 5a did not cause an alteration in the hemocyte density in Galleria mellonella larvae which is considered in vivo model for antimicrobial studies and was non-toxic up to a conc. of 2.5 mg/mL

Study the effect of heat processing on the vitamin C of some fruits

Ascorbic Acid also known as Vitamin C. Vitamin C is very essential for growth and maintenance of the human body. It is necessary for the normal formation of the protein collagen, which is an important constituent of skin and connective tissue. The deficiency of vitamin C causes will be known as disease “Scurvyâ€. Vitamin C is present in all citrus fruits, gooseberry (Aonala), tomato, apple, pine, pineapple, grapes and other foods. The vitamin C is very sensitive to heat light air and strong alkali. In this paper, we study the effect of heat processing on the vitamin C of Citrus Limon, Ananas Cosmosus, Psidium Guajana, Vitis Vinifera

Determination of distances and sizes of visible objects using a plane transparent glass plate

A novel approach for the determination of distances and sizes of the different visible objects has been proposed. Accordingly, an experimental set up has been designed. This method is cheap, handy and easy to use. Observations are conducted with the help of a plane transparent glass plate and a travelling microscope. Distances and sizes calculated with this method are found to be in good agreement with those of the reported values

New biologically active allelochemical from seeds of <i style="mso-bidi-font-style:normal">Cassia absus </i>Linn.

953-957A new bioactive allelochemical 1, m.p. 235-36°C, m.f. C34H42O20, [M]+ 770 (FABMS), has been isolated from methanolic extract of the seeds of Cassia absus Linn. alongwith two known compounds 3, 5, 7, 4′-tetrahydroxy-2′, 5′-dimethoxy flavone and Luteolin. The structure of a new compound has been characterized as 5, 7, 4′-trihydroxy-8,3′-dimethoxyflavone-5-O-α--rhamnopyranosyl-7-O-β--xylopyranosyl-(1→4)-O-β--galacto­­pyranoside by various colour reactions, spectral analysis and chemical degradations. All the secondary plant metabolites are called allelochemicals. </span

Molecular dynamics simulation of hydrated d(CGGGTACCCG)₄ as a four-way DNA Holliday junction and comparison with the crystallographic structure

<div><p>Molecular dynamics (MD) simulation of decamer sequence (CGGGTACCCG)₄ as a four-way Holliday junction is reported here for 15.0 ns at three different temperatures 100, 200 and 300 K, respectively, using AMBER force field. Particle mesh Ewald method has been utilised to deal long-range interaction potentials. After MD simulation, various parameters of the junction model including backbone and helical parameters have been worked out and the dynamical pathway is discussed. Structural analysis and geometrical calculations were carried out through X3DNA. The computational results obtained are compared with the previously reported crystallographic outcomes. The width and depth of the major and minor grooves of the duplex of the four arms of the DNA junction have been calculated. The variations in the C1′–C1′ distances between the two complementary strands are discussed in detail. A close observation of the results reveals that the conformation of the average simulated structure at low temperature is of ‘B’ form and the structural integrity of the DNA junction having a twofold sequence symmetry is temperature dependent. It also seems that besides the other parameters (i.e. presence of ions, solvents, etc.), temperature may be playing a key role in preserving the structural integrity of the DNA junction.</p></div

Evaluation of caffeine as inhibitor against collagenase, elastase and tyrosinase using in silico and in vitro approach

Skin ageing results from enhanced activation of intracellular enzymes such as collagenases, elastases and tyrosinase, stimulated by intrinsic ageing and photoageing factors. Recently, caffeine-based cosmetics are introduced that demonstrates to slow down skin photoageing process. However, no attempts have been done so for to understand caffeine functional inhibitory activity against photoageing related enzymes. Hence, this study established the caffeine molecular interaction and inhibition activity profiles against respective enzymes using in silico and in vitro methods, respectively. Results from in silico study indicates that caffeine has comparatively good affinity with collagenase (−4.6 kcal/mol), elastase (−3.36 kcal/mol) and tyrosinase (−2.86 kcal/mol) and formed the stable protein-ligand complex as validated by molecular dynamics simulation (protein-ligand contacts, RMSD, RMSF and secondary structure changes analysis). Moreover, in vitro data showed that caffeine (1000 µg/mL) has statistically significant maximum inhibition activity of 41.86, 36.44 and 13.72% for collagenase, elastase and tyrosinase, respectively

SWIFT J0503.7-2819: A nearly synchronous intermediate polar below the period gap?

Based on the X-ray observations from XMM-Newton and Swift, and optical observations from Transiting Exoplanet Survey Satellite (TESS) and AAVSO, we present temporal and spectral properties of probable intermediate polar SWIFT J0503.7-2819. The X-ray light curve shows two distinctive features, where possibly the second pole seems to be active during the middle of the XMM-Newton observations. Present analysis confirms and also refines the previously reported orbital period of SWIFT J0503.7-2819 as 81.65±0.04 min. The X-ray and optical variations of this target have been found to occur at the period of ∼ 65 min, which we propose as the spin period of the white dwarf (WD). The energy-dependent modulation at this period, which are due to the photoelectric absorption in the accretion flow, also assures this conjecture. Two temperature thermal plasma model well explains the X-ray spectra with temperatures of ∼ 150 eV and ∼ 18.5 keV, which is absorbed by a dense material with an average equivalent hydrogen column density of 3.8 × 1022 cm−2 that partially covers ∼ 27% of the X-ray source. An attempt is made to understand the accretion flow in this system using the present data of SWIFT J0503.7-2819. If the proposed spin period is indeed the actual period, then SWIFT J0503.7-2819 could be the first nearly synchronous intermediate polar below the period gap

Structure-based screening and validation of bioactive compounds as Zika virus methyltransferase (MTase) inhibitors through first-principle density functional theory, classical molecular simulation and QM/MM affinity estimation

Recent Zika virus (ZIKV) outbreak and association with human diseases such as neurological disorders have raised global health concerns. However, in the absence of an approved anti-ZIKV drug has generated urgency for the drug development against ZIKV infection. Here, structure-based virtual screening of 8589 bioactive compounds, screened at the substrate-binding site of ZIKV nonstructural 5 (NS5)-based structure N-terminal methyltransferase (MTase) domain followed by ADMET (absorption, distribution, metabolism, excretion and toxicity) profiling concluded the four potential lead inhibitors, i.e. (4-acetylamino-benzenesulfonylamino)-acetic acid (F3342-0450), 3-(5-methylfuran-2-yl)-N-(4-sulfamoylphenyl)propanamide (F1736-0142), 8-(2-hydroxy-ethylamino)-1,3-dimethyl-7-(3-methyl-benzyl)-3,7-dihydro-purine-2,6-dione (F0886-0080) and N-[4-(aminosulfonyl)phenyl]-2,3-dihydro-1,4-benzodioxine-2-carboxamide (F0451-2187). Collectively, extra precision docking and Density Functional Theory(DFT) calculations studies identified the F3342-0450 molecule, having strong interactions on the active site of MTase, further supported by molecular dynamics simulation, binding affinity and hybrid QM/MM calculations, suggest a new drug molecule for the antiviral drug development against ZIKV infection. Communicated by Ramaswamy H. Sarma