31 research outputs found
SYNTHESIS, MOLECULAR MODELING, AND QUANTITATIVE STRUCTURE–ACTIVITY RELATIONSHIP STUDIES OF UNDEC-10-ENEHYDRAZIDE DERIVATIVES AS ANTIMICROBIAL AGENTS
Objective: In recent years, an increasing frequency and severity of antimicrobial resistance to different antimicrobial agents, demands new remedies for the treatment of infections. Therefore, in this study, a series of undec-10-enehydrazide derivatives were synthesized and screened for in vitro activity against selected pathogenic microbial strains.Methods: The synthesis of the intermediate and target compounds was performed by standard procedure. Synthesized compounds were screened for antimicrobial activity by tube dilution method. Molecular docking study of synthesized derivatives was also performed to find out their interaction with the target site of β-ketoacyl-acyl carrier protein synthase III, (FabH; pdb id:3IL7) by docking technique. Quantitative structure–activity relationship (QSAR) studies were also performed to correlate antimicrobial activity with structural properties of synthesized molecules.Results: Antimicrobial screening results showed that compound 8 having benzylidine moiety with methoxy groups at meta and para position and compound 16 having 3-chloro-2-(3-flourophenyl)-4-oxoazetidine moiety was found to be most potent. QSAR studies revealed the importance of Randic topology parameter (R) in describing the antimicrobial activity of synthesized derivatives. Molecular docking study indicated hydrophobic interaction of deeply inserted aliphatic side chain of the ligand with FabH. The N-atoms of hydrazide moiety interacts with Ala246 and Asn247 through H-bonding. The m- and p-methoxy groups form H-bond with water and side chain of Arg36, respectively.Conclusion: Compound 8 having benzylidine moiety with methoxy groups at meta and para position and compound 16 having 3-chloro-2-(3- flourophenyl)-4-oxoazetidine moiety was found to most potent antibacterial and antifungal compounds, respectively
A COMPARATIVE STUDY OF STEREOCHEMICAL EFFECTS OF ANTI-PROSTATE AGENTS BY MOLECULAR DOCKING
Objective: A comparative study of anti-prostate agents to investigate the stereochemical influences on binding affinity by molecular docking.Methods: Structures of enantiomers (R and S stereoisomers) for known anti-prostate cancer (PCa) agents were drawn using ChemBioDraw 2D software. Thereafter, they were converted to 3D structures using the ChemBioDraw 3D software in which they were subjected to energy minimization using the MM2 method and then saved as PDB extension files which can be accessed using the ADT interface. AutoDock Vina (ADT) 1.5.6 software version was used for molecular docking study.Results: A total of 12 different anti-PCa agents were selected and drawn including well-known drug R-bicalutamide. All molecules showed the binding affinity with respect to the nature of stereochemistry. R-stereoisomers showed better interaction as well as binding affinity toward 1z95 (mutated androgen receptor protein involved in the progression of PCa) whereas their S-stereoisomers were found inferior in comparison.Conclusion: This study showed that CB1-R and R-bicalutamide (with R-stereochemistry) were better in binding affinity comparative to their counterpart CB1-S and S-Bicalutamide (with S-stereochemistry). All the selected anti-PCa agents were showing the effect of stereochemical center; therefore, we must choose the right kind of stereochemistry while planning to develop the newer anti-PCa agents
Fabrication of α‑Fe2O3 Nanostructures: synthesis, characterization, and their promising application in the treatment of Carcinoma A549 Lung Cancer Cells
In the present work, iron nanoparticles were synthesized in the α-Fe2O3 phase with the reduction of potassium hexachloroferrate(III) by using l-ascorbic acid as a reducing agent in the presence of an amphiphilic non-ionic polyethylene glycol surfactant in an aqueous solution. The synthesized α-Fe2O3 NPs were characterized by powder X-ray diffraction, field emission scanning electron microscopy, transmission electron microscopy, atomic force microscopy, dynamic light scattering, energy dispersive X-ray spectroscopy, Fourier transform infrared spectroscopy, and ultraviolet–visible spectrophotometry. The powder X-ray diffraction analysis result confirmed the formation of α-Fe2O3 NPs, and the average crystallite size was found to be 45 nm. The other morphological studies suggested that α-Fe2O3 NPs were predominantly spherical in shape with a diameter ranges from 40 to 60 nm. The dynamic light scattering analysis revealed the zeta potential of α-Fe2O3 NPs as −28 ± 18 mV at maximum stability. The ultraviolet–visible spectrophotometry analysis shows an absorption peak at 394 nm, which is attributed to their surface plasmon vibration. The cytotoxicity test of synthesized α-Fe2O3 NPs was investigated against human carcinoma A549 lung cancer cells, and the biological adaptability exhibited by α-Fe2O3 NPs has opened a pathway to biomedical applications in the drug delivery system. Our investigation confirmed that l-ascorbic acid-coated α-Fe2O3 NPs with calculated IC50 ≤ 30 μg/mL are the best suited as an anticancer agent, showing the promising application in the treatment of carcinoma A549 lung cancer cells
Mapping local patterns of childhood overweight and wasting in low- and middle-income countries between 2000 and 2017
A double burden of malnutrition occurs when individuals, household members or communities experience both undernutrition and overweight. Here, we show geospatial estimates of overweight and wasting prevalence among children under 5 years of age in 105 low- and middle-income countries (LMICs) from 2000 to 2017 and aggregate these to policy-relevant administrative units. Wasting decreased overall across LMICs between 2000 and 2017, from 8.4% (62.3 (55.1–70.8) million) to 6.4% (58.3 (47.6–70.7) million), but is predicted to remain above the World Health Organization’s Global Nutrition Target of <5% in over half of LMICs by 2025. Prevalence of overweight increased from 5.2% (30 (22.8–38.5) million) in 2000 to 6.0% (55.5 (44.8–67.9) million) children aged under 5 years in 2017. Areas most affected by double burden of malnutrition were located in Indonesia, Thailand, southeastern China, Botswana, Cameroon and central Nigeria. Our estimates provide a new perspective to researchers, policy makers and public health agencies in their efforts to address this global childhood syndemic
Search for gravitational-lensing signatures in the full third observing run of the LIGO-Virgo network
Gravitational lensing by massive objects along the line of sight to the source causes distortions of gravitational wave-signals; such distortions may reveal information about fundamental physics, cosmology and astrophysics. In this work, we have extended the search for lensing signatures to all binary black hole events from the third observing run of the LIGO--Virgo network. We search for repeated signals from strong lensing by 1) performing targeted searches for subthreshold signals, 2) calculating the degree of overlap amongst the intrinsic parameters and sky location of pairs of signals, 3) comparing the similarities of the spectrograms amongst pairs of signals, and 4) performing dual-signal Bayesian analysis that takes into account selection effects and astrophysical knowledge. We also search for distortions to the gravitational waveform caused by 1) frequency-independent phase shifts in strongly lensed images, and 2) frequency-dependent modulation of the amplitude and phase due to point masses. None of these searches yields significant evidence for lensing. Finally, we use the non-detection of gravitational-wave lensing to constrain the lensing rate based on the latest merger-rate estimates and the fraction of dark matter composed of compact objects
Search for eccentric black hole coalescences during the third observing run of LIGO and Virgo
Despite the growing number of confident binary black hole coalescences observed through gravitational waves so far, the astrophysical origin of these binaries remains uncertain. Orbital eccentricity is one of the clearest tracers of binary formation channels. Identifying binary eccentricity, however, remains challenging due to the limited availability of gravitational waveforms that include effects of eccentricity. Here, we present observational results for a waveform-independent search sensitive to eccentric black hole coalescences, covering the third observing run (O3) of the LIGO and Virgo detectors. We identified no new high-significance candidates beyond those that were already identified with searches focusing on quasi-circular binaries. We determine the sensitivity of our search to high-mass (total mass M>70 M⊙) binaries covering eccentricities up to 0.3 at 15 Hz orbital frequency, and use this to compare model predictions to search results. Assuming all detections are indeed quasi-circular, for our fiducial population model, we place an upper limit for the merger rate density of high-mass binaries with eccentricities 0<e≤0.3 at 0.33 Gpc−3 yr−1 at 90\% confidence level
Ultralight vector dark matter search using data from the KAGRA O3GK run
Among the various candidates for dark matter (DM), ultralight vector DM can be probed by laser interferometric gravitational wave detectors through the measurement of oscillating length changes in the arm cavities. In this context, KAGRA has a unique feature due to differing compositions of its mirrors, enhancing the signal of vector DM in the length change in the auxiliary channels. Here we present the result of a search for U(1)B−L gauge boson DM using the KAGRA data from auxiliary length channels during the first joint observation run together with GEO600. By applying our search pipeline, which takes into account the stochastic nature of ultralight DM, upper bounds on the coupling strength between the U(1)B−L gauge boson and ordinary matter are obtained for a range of DM masses. While our constraints are less stringent than those derived from previous experiments, this study demonstrates the applicability of our method to the lower-mass vector DM search, which is made difficult in this measurement by the short observation time compared to the auto-correlation time scale of DM
Stereochemistry of Dihydropyrimidinones Derivatives Synthesized by Brick Dust Catalytic Reaction
A number of catalytic synthetic reactions have been reported which play the important role in stereochemistry of compounds. The key to the success of this protocol was the generation of stereogenic centers in 1, 4-Dihydropyrimidinones (DHPMs) and the influence of catalysts on their configuration. Waste brick dust was found to be an effective catalyst, generating chiral DHPMs derivatives using aryl aldehyde, urea, and ethyl acetoacetate. This work mainly focuses on the stereochemistry of brick-dust catalyzed DHPMs derivatives. Discovery of brick dust catalyst associated with several benefits such as rapid clean reaction, simple, and ease work-up
A questionnaire study on the knowledge, attitude, and the practice of pharmacovigilance among the healthcare professionals in a teaching hospital in South India
Objective: The primary objective of this study was to evaluate the knowledge, attitude, and practices (KAP) of the healthcare professionals about pharmacovigilance in Dhanalakshmi Srinivasan Medical College and Hospital (DSMCH), Perambalur (Tamil Nadu), a tertiary care teaching hospital. The second primary objective was to assess the causation of underreporting of adverse drug reactions (ADRs) as it needs to be well-assessed in India. The secondary objective was to compare the findings of this study with the results of the published studies from India on evaluation of the KAP of pharmacovigilance among healthcare professional. Materials and Methods: A cross-sectional study was carried out using a pretested questionnaire. The questionnaire was designed to assess the KAP regarding pharmacovigilance. The healthcare professionals (doctors, nurses, and pharmacists) working in the DSMCH, Perambalur (Tamil Nadu) during the study period were included. Only those who gave their consent to participate were included in the study. The data was analyzed by using the Statistical Package for Social Sciences (SPSS) statistical software, version 16. Results: One hundred and fifty pretested questionnaires were distributed among the healthcare professionals and 101 responded. 62.4% healthcare workers gave correct response regarding the definition of pharmacovigilance. 75.2% of healthcare workers were aware regarding the existence of a National Pharmacovigilance Program of India. 69.3% healthcare professional agreed that ADR reporting is a professional obligation for them. Among the participants, 64.4% have experienced ADRs in patients, but only 22.8% have ever reported ADR to pharmacovigilance center. Unfortunately only 53.5% healthcare workers have been trained for reporting adverse reactions. But, 97% healthcare professionals agreed that reporting of ADR is necessary and 92.1% were of the view that pharmacovigilance should be taught in detail to healthcare professional. Conclusion: This study demonstrated that knowledge and attitude towards pharmacovigilance is gradually improving among healthcare professionals, but unfortunately the actual practice of ADR reporting is still deficient among them