Sharda University

About: Sharda University is a education organization based out in Greater Noida, Uttar Pradesh, India. It is known for research contribution in the topics: Computer science & Medicine. The organization has 1276 authors who have published 2012 publications receiving 16188 citations.

Screening of promising molecules against MurG as drug target in multi-drug-resistant-Acinetobacter baumannii - insights from comparative protein modeling, molecular docking and molecular dynamics simulation.

Abstract: The UDP-N-acetylglucosamine-N-acetylmuramyl-(pentapeptide) pyrophosphoryl-undecaprenol N-acetylglucosamine transferase (MurG) is located in plasma membrane which plays a crucial role for peptidoglycan biosynthesis in Gram-negative bacteria. Recently, this protein is considered as an important and unique drug target in Acinetobacter baumannii since it plays a key role during the synthesis of peptidoglycan as well as which is not found in Homo sapiens. In this study, initially we performed comparative protein modeling approach to predict the three-dimensional model of MurG based on crystal structure of UDP-N-acetylglucosamine-N-acetylmuramyl-(pentapeptide) pyrophosphoryl-undecaprenol N-acetylglucosamine transferase (PDB ID: 1F0K) from E.coli K12. MurG model has two important functional domains located in N and C- terminus which are separated by a deep cleft. Active site residues are located between two domains and they are Gly20, Arg170, Gly200, Ser201, Gln227, Phe254, Leu275, Thr276, and Glu279 which play essential role for the function of MurG. In order to inhibit the function of MurG, we employed the High Throughput Virtual Screening (HTVS) and docking techniques to identify the promising molecules which will further subjected into screening for computing their drug like and pharmacokinetic properties. From the HTVS, we identified 5279 molecules, among these, 12 were passed the drug-like and pharmacokinetic screening analysis. Based on the interaction analysis in terms of binding affinity, inhibition constant and intermolecular interactions, we selected four molecules for further MD simulation to understand the structural stability of protein-ligand complexes. All the analysis of MD simulation suggested that ZINC09186673 and ZINC09956120 are identified as most promising putative inhibitors for MurG protein in A. baumannii.Communicated by Ramaswamy H. Sarma.

Antimicrobial resistance dynamics and the one-health strategy: a review

Abstract: Antimicrobial resistance is a global threat that kills at least 75,000 people every year worldwide and causes extended hospital stays. In the coming 10 years, antimicrobial resistance is projected to have huge health and economic burden on countries, and the scarcity of available antibiotics further worsens the situation. Antimicrobial resistance results mainly from indiscriminate antibiotic usage in humans, animals and agriculture, and from the rapid emergence and dissemination of resistant pathogens. This issue is challenging for antibiotic stewardship, strict regulations on antibiotics usage, large-scale surveillance and responsible public behavior. This demands international cooperation and integrated efforts under the ‘one-health’ strategy. Here, we review antimicrobial resistance and the one-health strategy. We discuss the historical issue of using antibiotics. We highlight the effectiveness of hygiene in livestock rearing, careful antibiotic usage and large-scale surveillance of animals, humans and environment domains. We present strategies for mitigation of antimicrobial resistance, exemplified by the successful ban of triclosan which induced a significant decline of resistant pathogens. We emphasize the benefits of the global antibiotic resistance partnership and of the one-health participation of stakeholders from public, healthcare professionals and government to mitigate antimicrobial resistance.

A Randomized Controlled Trial Study on the Effect of Adding Dexmedetomidine to Bupivacaine in Supraclavicular Block Using Ultrasound Guidance.

Abstract: BACKGROUND: The benefits of regional anesthetic techniques are well established. Use of additives tolocal anesthetics can prolong these benefits. The aim of this study was to find out the effect of addingdexmedetomidine to bupivacaine for supraclavicular block.METHODS: In this randomized, double-blind study, 70 ASA I & II patients of either sex undergoingelective surgeries on the upper limb were given supraclavicular block under ultrasound guidance. GroupC (n=35) received 38 mL 0.25% bupivacaine + 2mL normal saline and group D received 38 mL 0.25%bupivacaine + 1 μg/kg dexmedetomidine (2mL). Patients were observed for, onset of motor and sensoryblock, duration of motor and sensory block, duration of analgesia, sedation score, hemodynamic changesand any adverse events.RESULTS: In group D, the onset was faster (P< 0.001), durations of sensory and motor block durationof and analgesia were prolonged as compared to group C (P < 0.0001).There was a significant drop inheart rate (HR) from the baseline in group D (P < 0.05) at 30, 60, 90 and 120 min. However, none of thepatients dropped HR below 50/min. Mean Arterial Pressure (MAP) remained unaffected. The patients ingroup D were more effectively sedated than those in group C (P < 0.05). No adverse event was reported ineither group.CONCLUSION: Dexmedetomidine as adjuvant to bupivacaine in supraclavicular block resulted in fasteraction, prolonged motor and sensory block, prolonged analgesia with hemodynamic stability andadequate sedation.

Group 12 metal complexes of (2-piperazine-1-yl-ethyl)-pyridin-2-yl-methylene-amine: rare participation of terminal piperazine N in coordination leads to structural diversity

Abstract: By using a potential tridentate ligand L ((2-piperazine-1-yl-ethyl)-pyridin-2-yl-methylene-amine), a series of group 12 metal complexes namely, [ZnLHCl2][Zn2LCl5]·2H2O (1), [CdL(SCN)2(CH3OH)]n (2), and [Hg(l-pyCO)Cl2] (3), were synthesized and structurally characterized. In all the complexes the piperazine nitrogen of the ligand takes part in coordination and leads to the complexes of group 12 metal ions having structural diversity. The X-ray diffraction analysis of complex 1 indicates for one Zn(ii) ion a geometry in between trigonal bipyramidal/square pyramidal and for the second a distorted tetrahedral sphere. In the polymeric complex 2 the Cd(ii) ion shows a distorted octahedral environment, while in the mononuclear complex 3, where Hg(ii) exhibits a square-pyramidal geometry, an unexpected condensation between the uncoordinated NH piperazine fragment with 2-pyridinecarboxaldehyde was detected. The M-N bond lengths in all the complexes are in accordance with the metal ionic radius. Continuous shape measures through a DFT approach provide the coordination environment around each metal centre that is comparable with the experimental observations. We have also investigated the importance of hydrogen bonding of methanol in the generation of the polymeric Cd complex 2 along with the rearrangement of the tridentate ligand to generate an octahedral complex. The photoluminescence properties of the complexes as well as of the ligand were investigated in solution at ambient temperature. The low quantum yield of the ligand was ascribed due to a very fast photoinduced electron transfer (PET) from the nitrogen lone pair to the conjugated pyridine moiety. Complexation prevents the electron transfer, and consequently an increase in quantum yield was observed in the complexes. Among the three complexes the highest photoluminescence was exhibited by a Zn complex, being lower in Cd and Hg complexes as a consequence of the heavy atom perturbation effect.