Showing papers by "Hirdyesh Mishra published in 2014"

Stabilization of high temperature hexagonal phase of SrAl2O4 at room temperature: role of ZnO

Abstract: Strontium aluminate (SrAl2O4) exhibits a monoclinic structure at room temperature (RT) and transforms to a hexagonal structure at above 650 °C, reported previously in the literature. In this article, we have shown a stable, high temperature hexagonal phase of SrAl2O4 (SAO) at RT by synthesizing a SAO–ZnO composite through a combustion technique. While SAO crystallizes in the monoclinic phase by adding 2.5 wt% of ZnO, a stable hexagonal phase of SAO at RT has been obtained for 20 wt% of ZnO. Further, the hexagonal phase of SAO transforms to a monoclinic phase after increasing the calcination temperature from 700 to 1200 °C. The role of ZnO in determining the structure and photoluminescence properties of these composites are discussed.

Metal-Enhanced S1 and Alpha- S1 Fluorescence: Effects of Far-Field Excitation Irradiance on Enhanced Fluorescence

Abstract: Metal-enhanced fluorescence (MEF) and delayed fluorescence (alpha α-S1) studies of acriflavin have been undertaken using steady-state and time-resolved fluorescence measurements on silver island films (SiFs) supporting a thin poly(vinyl alcohol) (PVA) polymer film. Nearly a 3.5-fold enhancement in the far-field fluorescence intensity of acriflavin is observed coupled with a decrease in decay times and an improved fluorophore photostability. Our findings are consistent with our proposed model of the coupling and transferring of the excited state energies of fluorophores to silver surface plasmons. Further, an excitation power dependence of MEF is observed in these films, consistent with our postulate of MEF EVE (MEF excitation volumetric effect) and, ultimately, resulting in a ∼7-fold enhancement in fluorescence intensity. Our findings suggest a significant opportunity for the development of shorter-lived, brighter, high photon flux luminescent materials for multifarious applications in the life-sciences.

Examining structural analogs of elvitegravir as potential inhibitors of HIV-1 integrase

Abstract: Acquired immunodeficiency syndrome (AIDS) is a major health problem in many parts of the world. The human immunodeficiency virus-1 integrase (HIV-1 IN) enzyme has been targeted in HIV patients for therapy. Several integrase inhibitors have been reported, but only elvitegravir (EVG), a new-generation drug, is clinically approved for HIV treatment. In the present work, we investigated two structural analogs of EVG as potential inhibitors of the target molecule, HIV-1 IN. The ligand binding site on HIV-1 IN was identified using Q-SiteFinder, and the HIV-1 IN protein was docked with ligand (EVG and/or analogs) using AutoDock 4. The results suggest that Lys173, Thr125, and His171 are involved in enzyme-substrate binding through hydrogen bonds. Single mutations carried out at Lys173, viz. Lys173Leu (polar > nonpolar) and Lys173Gln (polar > polar), in chain B using PyMOL showed the mutants to have lower binding energy when docked with analog 2, suggesting it to be more stable than analog 1. In conclusion, the mutant HIV-1 IN can bind EVG and its analogs. The physicochemical and pharmacokinetic parameters also show analog 2 to be a promising molecule that can be developed as an alternative to EVG to help overcome the problem of drug resistance by HIV to this inhibitor. Analog 2 may be used as an HIV-1 IN inhibitor with similar potential to that of EVG. Further validation through wet-lab studies, however, is required for future applications.

Evaluation of novel Saquinavir analogs for resistance mutation compatibility and potential as an HIV-Protease inhibitor drug.

Abstract: A fundamental issue related to therapy of HIV-1 infection is the emergence of viral mutations which severely limits the long term efficiency of the HIV-protease (HIV-PR) inhibitors. Development of new drugs is therefore continuously needed. Chemoinformatics enables to design and discover novel molecules analogous to established drugs using computational tools and databases. Saquinavir, an anti-HIV Protease drug is administered for HIV therapy. In this work chemoinformatics tools were used to design structural analogs of Saquinavir as ligand and molecular dockings at AutoDock were performed to identify potential HIV-PR inhibitors. The analogs S1 and S2 when docked with HIV-PR had binding energies of -4.08 and -3.07 kcal/mol respectively which were similar to that for Saquinavir. The molecular docking studies revealed that the changes at N2 of Saquinavir to obtain newly designed analogs S1 (having N2 benzoyl group at N1) and S2 (having 3-oxo-3phenyl propanyl group at N2) were able to dock with HIV-PR with similar affinity as that of Saquinavir. Docking studies and computationally derived pharmacodynamic and pharmacokinetic properties׳ comparisons at ACD/I-lab establish that analog S2 has more potential to evade the problem of drug resistance mutation against HIV-1 PR subtype-A. S2 can be further developed and tested clinically as a real alternative drug for HIV-1 PR across the clades in future.