ANTIMICROBIAL AND IN SILICO ADMET SCREENING OF NOVEL (E)-N-(2-(1H-INDOL-3-YL-AMINO) VINYL)-3-(1-METHYL-1H-INDOL-3-YL)-3-PHENYLPROPANAMIDE DERIVATIVES

Objective: Synthesis, in silico absorption, distribution, metabolism, excretion, toxicity (ADMET) and in vitro antimicrobial screening of (E)-N-(2-(1H-indol-3-ylamino) vinyl)-3-(1-methyl-1H-indol-3-yl)-3-phenylpropanamide derivatives.Methods: (E)-N-(2-(1H-indol-3-ylamino) vinyl)-3-(1-methyl-1H-indol-3-yl)-3 phenylpropane-amide derivatives were synthesized by combining indole ethanolamine and substituted Meldrum's adduct. The synthesized compounds were subjected to in vitro antimicrobial study by cup plate method and in silico ADMET properties using ACD/I-Lab 2.0.Results: The in vitro antimicrobial screening against precarious pathogenic microorganisms viz, Pseudomonas aureginosa, Staphylococcus aureus, Escherichia coli, Vibrio cholerae, and the antifungal activity against Candida albicans, Aspergillus niger, Penicillin chrysogenum and Cladosporium oxysporum strains. The results revealed that compounds 5b, 5c, 5d and 5e showed good antimicrobial property and obeyed the in silico pharmacokinetic parameters.Conclusion: The encouraging results exhibited by the compounds (E)-N-(2-(1H-indol-3-ylamino) vinyl)-3-(1-methyl-1H-indol-3-yl)-3-phenyl propanamide derivatives, 5(a-e) can be explored as possible hits in antimicrobial therapy. The molecules obey the Lipinski rule of five when tested in silico and can be used in understanding the quantitative structure-activity relationship (QSAR) parameters

ANTIPROLIFERATIVE, ADME AND POTENTIAL IN SILICO G6PDH INHIBITORY ACTIVITY OF NOVEL 2-(1-BENZOFURAN-2-YL)-4-(5-PHENYL-4H-1, 2, 4-TRIAZOL-3-YL) QUINOLINE DERIVATIVES

Objectives: Synthesis of new 2-(1-benzofuran-2-yl)-4-(5-phenyl-4H-1, 2, 4-triazol-3-yl) quinoline and its derivatives for antiproliferative potential against cancer cells.Methods: The general methods were employed for the synthesis and the structures were confirmed by IR, 1H-NMR, 13C-NMR and mass spectral analysis. The antiproliferative activity was performed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and molecular docking study were performed by Auto Dock Tools. In silico Absorption-Distribution-Metabolism-Excretion-Toxicity (ADMET) study for the drug, likeliness was carried out on ACD/lab-2.Results: The compound 3l showed 44, 44, 38 and 37 % inhibition against MCF-7, HepG2, Colo205 and HeLa cell lines, respectively; whereas, the compounds 3i and 3j exhibited 49 and 42 % inhibition against MCF-7 cell line. The molecular docking study revealed that the compound 3i has the lowest binding energy (-8.60 Kcal mol-1), suggesting to be potentially best inhibitor of Glucose-6-phosphate dehydrogenase (G6PDH). The in silico ADME analysis also revealed that compound 3i does not violate any of the Lipinski rules of five and has the best stimulative human colonic absorption up to 95 %.Conclusion: The study reveals that the compounds containing benzofuran coupled nitrogen heterocycles are essential for activity as they possess excellent drug-like characteristics.Â

Novel Synthesis of 3-(Phenyl) (Ethylamino) Methyl)-4-Hydroxy-2H-Chromen-2-one Derivatives Using Biogenic ZnO Nanoparticles and their Applications

Received: 29.11.2021. Revised: 15.01.2022. Accepted: 15.01.2022. Available online: 21.01.2022.The authors declare that there are no conflicts of interests regarding the publication of this work.The present work describes the novel synthesis of 3, 3-((phenyl) (ethylamino) methyl)-4-hydroxy-2H-chromen-2-one derivatives catalyzed by biogenic ZnO nanoparticles. The synthesized heterocyclic compounds were characterized by fourier-transform infrared spectroscopy (FT-IR), nuclear magnetic resonance (NMR) and mass spectrometric techniques. Absorption, distribution, metabolism and excretion properties and various toxicities (ADMET) studies and in silico molecular docking studies were carried out for the synthesized compounds. The synthesized compounds were screened for their efficacy towards the antioxidant activity and were subjected to corrosion inhibition study towards the mild steel in acidic medium by weight loss method. Additionally, the recyclability of the employed catalyst was studied.The authors are thankful to the Chairman, Department of Chemistry, Kuvempu University Shankaraghatta for providing the laboratory facilities and to the University of Mysore and Saif Karnatak University, Dharwad for provid-ing spectra. One of the authors, Anjan Kumar G C thankful to the Council of Scientific and Industrial Research (CSIR), New Delhi, India, for providing a Junior Research fellow-ship [09/908(0010)/2019-EMR-I]

Facile ZnO NPs catalyzed synthesis of substituted 4-amino-6-(1H-benzimidazol-2-ylsulfanyl)benzene-1,3-dicarbonitrile new derivatives as Potent biological agents

This study focuses on the efficient synthesis of series of substituted 4-amino-6-(1H-benzimidazol-2-ylsulfanyl) benzene-1,3-dicarbonitrile derivatives synthesized from aldehydes, propanedinitrile, substituted thiols and catalyzed by ZnO nanoparticles (ZnONPs). All the synthesized compounds have been characterized using different spectroscopic techniques such as FT-IR, 1H-NMR, C13-NMR and Mass. The compounds were evaluated for potential pharmacological applications, including antimicrobial, α-amylase inhibitory and anticancer activities. Computational calculations, DFT, in-silico molecular docking, and ADME-toxicologystudies were performed. ADMET studies indicated that all synthesized compounds adhered to Rule of five with good bioavailability. This research underscores the promising pharmacological prospects of the synthesized newbenzimidazole derivatives

Gauge coupling unification with large extra dimensions

We make a detailed study of the unification of gauge couplings in the MSSM with large extra dimensions. We find some scenarios where unification can be achieved (with the strong coupling constant at the Z mass within one standard deviation of the experimental value) with both the compactification scale and the SUSY breaking scale in the few TeV range. No enlargement of the gauge group or particle content is needed. One particularly interesting scenario is when the SUSY breaking scale is larger than the compactification scale, but both are small enough to be probed at the CERN LHC. Unification in two scales scenarios is also investigated and found to give results within the LHC.Comment: 17 pages, 3 figures, some discussions added, few additional references included. Version to appear in Phys. Rev.

Discrimination of low missing energy look-alikes at the LHC

The problem of discriminating possible scenarios of TeV scale new physics with large missing energy signature at the Large Hadron Collider (LHC) has received some attention in the recent past. We consider the complementary, and yet unexplored, case of theories predicting much softer missing energy spectra. As there is enough scope for such models to fake each other by having similar final states at the LHC, we have outlined a systematic method based on a combination of different kinematic features which can be used to distinguish among different possibilities. These features often trace back to the underlying mass spectrum and the spins of the new particles present in these models. As examples of "low missing energy look-alikes", we consider Supersymmetry with R-parity violation, Universal Extra Dimensions with both KK-parity conserved and KK-parity violated and the Littlest Higgs model with T-parity violated by the Wess-Zumino-Witten anomaly term. Through detailed Monte Carlo analysis of the four and higher lepton final states predicted by these models, we show that the models in their minimal forms may be distinguished at the LHC, while non-minimal variations can always leave scope for further confusion. We find that, for strongly interacting new particle mass-scale ~600 GeV (1 TeV), the simplest versions of the different theories can be discriminated at the LHC running at sqrt{s}=14 TeV within an integrated luminosity of 5 (30) fb^{-1}.Comment: 40 pages, 10 figures; v2: Further discussions, analysis and one figure added, ordering of certain sections changed, minor modifications in the abstract, version as published in JHE

A community-based health education programme for bio-environmental control of malaria through folk theatre (Kalajatha) in rural India

BACKGROUND: Health education is an important component in disease control programme. Kalajatha is a popular, traditional art form of folk theatre depicting various life processes of a local socio-cultural setting. It is an effective medium of mass communication in the Indian sub-continent especially in rural areas. Using this medium, an operational feasibility health education programme was carried out for malaria control. METHODS: In December 2001, the Kalajatha events were performed in the evening hours for two weeks in a malaria-affected district in Karnataka State, south India. Thirty local artists including ten governmental and non-governmental organizations actively participated. Impact of this programme was assessed after two months on exposed vs. non-exposed respondents. RESULTS: The exposed respondents had significant increase in knowledge and change in attitude about malaria and its control strategies, especially on bio-environmental measures (p < 0.001). They could easily associate clean water with anopheline breeding and the role of larvivorous fish in malaria control. In 2002, the local community actively co-operated and participated in releasing larvivorous fish, which subsequently resulted in a noteworthy reduction of malaria cases. Immediate behavioural changes, especially maintenance of general sanitation and hygiene did not improve as much as expected. CONCLUSION: This study was carried out under the primary health care system involving the local community and various potential partners. Kalajatha conveyed the important messages on malaria control and prevention to the rural community. Similar methods of communication in the health education programme should be intensified with suitable modifications to reach all sectors, if malaria needs to be controlled

Testing gravitational-wave searches with numerical relativity waveforms: Results from the first Numerical INJection Analysis (NINJA) project

The Numerical INJection Analysis (NINJA) project is a collaborative effort between members of the numerical relativity and gravitational-wave data analysis communities. The purpose of NINJA is to study the sensitivity of existing gravitational-wave search algorithms using numerically generated waveforms and to foster closer collaboration between the numerical relativity and data analysis communities. We describe the results of the first NINJA analysis which focused on gravitational waveforms from binary black hole coalescence. Ten numerical relativity groups contributed numerical data which were used to generate a set of gravitational-wave signals. These signals were injected into a simulated data set, designed to mimic the response of the Initial LIGO and Virgo gravitational-wave detectors. Nine groups analysed this data using search and parameter-estimation pipelines. Matched filter algorithms, un-modelled-burst searches and Bayesian parameter-estimation and model-selection algorithms were applied to the data. We report the efficiency of these search methods in detecting the numerical waveforms and measuring their parameters. We describe preliminary comparisons between the different search methods and suggest improvements for future NINJA analyses.Comment: 56 pages, 25 figures; various clarifications; accepted to CQ

The Large Hadron-Electron Collider at the HL-LHC

The Large Hadron-Electron Collider (LHeC) is designed to move the field of deep inelastic scattering (DIS) to the energy and intensity frontier of particle physics. Exploiting energy-recovery technology, it collides a novel, intense electron beam with a proton or ion beam from the High-Luminosity Large Hadron Collider (HL-LHC). The accelerator and interaction region are designed for concurrent electron-proton and proton-proton operations. This report represents an update to the LHeC's conceptual design report (CDR), published in 2012. It comprises new results on the parton structure of the proton and heavier nuclei, QCD dynamics, and electroweak and top-quark physics. It is shown how the LHeC will open a new chapter of nuclear particle physics by extending the accessible kinematic range of lepton-nucleus scattering by several orders of magnitude. Due to its enhanced luminosity and large energy and the cleanliness of the final hadronic states, the LHeC has a strong Higgs physics programme and its own discovery potential for new physics. Building on the 2012 CDR, this report contains a detailed updated design for the energy-recovery electron linac (ERL), including a new lattice, magnet and superconducting radio-frequency technology, and further components. Challenges of energy recovery are described, and the lower-energy, high-current, three-turn ERL facility, PERLE at Orsay, is presented, which uses the LHeC characteristics serving as a development facility for the design and operation of the LHeC. An updated detector design is presented corresponding to the acceptance, resolution, and calibration goals that arise from the Higgs and parton-density-function physics programmes. This paper also presents novel results for the Future Circular Collider in electron-hadron (FCC-eh) mode, which utilises the same ERL technology to further extend the reach of DIS to even higher centre-of-mass energies.Peer reviewe

Search of the Orion spur for continuous gravitational waves using a loosely coherent algorithm on data from LIGO interferometers

We report results of a wideband search for periodic gravitational waves from isolated neutron stars within the Orion spur towards both the inner and outer regions of our Galaxy. As gravitational waves interact very weakly with matter, the search is unimpeded by dust and concentrations of stars. One search disk (A) is 6.87° in diameter and centered on 20h10m54.71s+33°33′25.29′′, and the other (B) is 7.45° in diameter and centered on 8h35m20.61s-46°49′25.151′′. We explored the frequency range of 50-1500 Hz and frequency derivative from 0 to -5×10-9 Hz/s. A multistage, loosely coherent search program allowed probing more deeply than before in these two regions, while increasing coherence length with every stage. Rigorous follow-up parameters have winnowed the initial coincidence set to only 70 candidates, to be examined manually. None of those 70 candidates proved to be consistent with an isolated gravitational-wave emitter, and 95% confidence level upper limits were placed on continuous-wave strain amplitudes. Near 169 Hz we achieve our lowest 95% C.L. upper limit on the worst-case linearly polarized strain amplitude h0 of 6.3×10-25, while at the high end of our frequency range we achieve a worst-case upper limit of 3.4×10-24 for all polarizations and sky locations. © 2016 American Physical Society