IDENTIFICATION OF ETHR INHIBITOR TARGETING MYCOBACTERIUM TUBERCULOSIS: AN INSIGHT FROM MOLECULAR DOCKING STUDY

Objective: Mycobacterium tuberculosis (MTB) is a pathogenic bacterium of the Mycobacteriaceae family that causes TB. EthR is a transcriptional regulator which is involved in the repression of the monooxygenase EthA which is responsible for the formation of the active metabolite of Eth. Inhibitors of the EthR DNA binding protein induce a conformational change in this repressor, thus preventing its binding to DNA operator, consequently resulting in increased transcription of EthA and bioactivation of Eth. Methods: In this study, we used first-line and second-line drugs and their analogues to validate the binding affinity of EthR DNA binding protein of MTB. Molegro Virtual Docker (MVD) is utilized for virtual screening and validation of MolDoc, Rerank, and hydrogen bond parameters of ETH, isoniazid (INH), clofazimine (CLF), and its modified derivatives to the EthR DNA binding protein of MTB. The modified molecules; ETH4, INZ2, CLF3, and CLF4 show more binding affinities than that of native compounds ETH, INH, and CLF to the EthR DNA binding protein of MTB. The top scoring compound was docked by auto dock vina in PyRx to get the best conformer pose for intermolecular interactions. Results: CLF4 had the best lowest MolDock score -176.29kcal/mol and H-bonding energy -6.89kcal/mol in the MVD virtual screening. The best conformer pose generated by PyRx was shown -7.1 binding affinity and ligand generated hydrogen bond interactions with THR130 and LYS68, respectively, which stabilized the ligand in the active site of EthR protein. Conclusion: We concluded that CLF4 has shown better inhibitory efficacy than other compounds towards EthR protein. However, these results need to be further substantiated through in vitro and in vivo experimental studies

Characterization of the first hexacoordinate phosphorus compound with S→P←S bonds

The first example of a hexacoordinate phosphorus compound [S{6-t-Bu-4-Me-C6H2O}2]2P+(Cl-· C3H4N2) with two S→P bonds is reported. This compound can be construed as an oxophosphonium salt with double intramolecular coordination by sulfur atoms. X-ray structure reveals a facial arrangement of the ligands with two coordinating sulfur atoms cis to each other. The S→P distance of 2.334 (1) Å is one among very short coordinate bond distances between sulfur and phosphorus

Phase field modelling of grain boundary premelting using obstacle potentials

We investigate the multi-order parameter phase field model of Steinbach and Pezzolla [I. Steinbach, F. Pezzolla, A generalized field method for multiphase transformations using interface fields, Physica D 134 (1999) 385-393] concerning its ability to describe grain boundary premelting. For a single order parameter situation solid-melt interfaces are always attractive, which allows to have (unstable) equilibrium solid-melt-solid coexistence above the bulk melting point. The temperature dependent melt layer thickness and the disjoining potential, which describe the interface interaction, are affected by the choice of the thermal coupling function and the measure to define the amount of the liquid phase. Due to the strictly finite interface thickness also the interaction range is finite. For a multi-order parameter model we find either purely attractive or purely repulsive finite-ranged interactions. The premelting transition is then directly linked to the ratio of the grain boundary and solid-melt interfacial energy.Comment: 12 page

Review on Sparse-Based Multipath Estimation and Mitigation: Intense Solution to Counteract the Effects in Software GPS Receivers

Multipath is the major concern in GPS receivers that fade the actual GPS signal causes positioning error up to 10 m so special care need to be taken to mitigate the multipath effects. Numerous methods like hardware based antenna arrays technique, receiver based narrow correlator receiver, double -delta discriminator, Adaptive Multipath Estimator, Wavelet Transformation and Particle filter, Kalman filter based post receiver methods etc. used to resolve the problem. But some of the methods can only reduce code multipath error but not effective in eliminating carrier multipath error. Most of these techniques are based on the assumption that the Line-of-Sight (LOS) signal is stronger than the Non-Line of-Sight (NLOS) signals. However, in the scenarios where the LOS signal is weaker than the composite multipath signal, this approach may result in a bias in code tracking. In this chapter, different types of multipath mitigation and its limitation are described. The recent development in sparse signal processing based blind channel estimation is investigated to compensate the multipath error. The Rayleigh and Rician fading model with different multipath parameters are simulated to test the urban scenario. The inverse problem of finding the GPS signal is addressed based on the deconvolution approach. To solve linear inverse problems, the suitable kind of appropriate objective function has been formulated to find the signal of interest. By exploiting this methods, the signal is observed and the carrier and code tracking loop parameters are computed with minimal error

The first structural study on a cyclic tricoordinate phosphorochloridite and a pentacoordinate phosphorane based on 1,2,3,5-protected myo-inositol-a new conformation of 1,3,2-dioxaphosphorinane ring

Treatment of the phosphoramidite {myo-C6H6-2-[OC(O)Ph]-1,3,5-(O3CH)-4,6-(O2P-NH-i-Pr)} with o-chloranil affords the first example of inositol-based pentacoordinate phosphorane {myo-C6H6-2-[OC(O)Ph]-1,3,5-(O3CH)-4,6-(O2P-NH-i-Pr)(1,2-O2C6Cl4)} (9) (X-ray structure) with a trigonal bipyramidal geometry at phosphorus. The six-membered 1,3,2-dioxaphosphorinane ring with the inositol residue has an unusual boat conformation in 9 which is quite different from that found in unrestrained rings investigated before, but is similar to that of its PIII chloro precursor {myo-C6H6-2-[OC(O)Ph]-1,3,5-(O3CH)-4,6-(O2PCl)} (X-ray structure). Also, a convenient and chromatography-free procedure for the protected myo-inositol derivative {myo-C6H6-2-[OC(O)Ph]-1,3,5-(O3CH)-4,6-(OH)2} is reported

BIOLOGICAL ACTIVITIES OF ALTERNARIA SP. RL4 – A POTENT ENDOPHYTIC FUNGUS ASSOCIATED WITH RAUVOLFIA SERPENTINA L. BENTH.

Objectives: Endophytic fungi are considered as an important source of bioactive metabolites. The present study focused on the isolation of potent endophytic fungal strains from well-known medicinal plant Rauvolfia serpentina L. Benth. having biological activities.Materials & Methods: Fungal endophytes were isolated from aerial parts of the plant and the potent strain was selected on the basis of antibacterial activities of cell-free supernatant (CFS). Ethyl acetate (EA) extraction of CFS was done and mode of action of EA fraction was checked against pathogenic bacteria. EA fraction was also analyzed by thin-layer chromatography (TLC). In addition, antioxidant activity was checked by 1,1-Diphenyl- 2-picrylhydrazyl-free radical scavenging assay and anticancer activity was checked against breast cancer cell line MCF-7 by MTT assay.Results: Among the different endophytic fungal isolates, CFS of Alternaria sp. RL4 produced prominent zones of inhibition against numbers of Gram-positive pathogenic bacteria including Staphylococcus aureus (12±0.5 mm) and Listeria monocytogenes (17±2.0 mm). Massive reductions in bacterial CFS were noticed upon treatment with EA fraction (2 mg/ml). It also showed strong cidal mode of action against Gram-positive organisms. TLC analysis revealed the production of two different compounds with antibacterial potentials. In addition, EA fraction of RL4 showed very good antioxidant property with an IC50 value of 49.80±2.11μg/ml. MTT assay also suggested the anticancerous properties of EA fraction of RL4.Conclusion: Alternaria sp. RL4 could be a very good source of bioactive compounds for the development of new drugs

Development and validation of new analytical method for the simultaneous estimation of omeprazole and domperidone in pharmaceutical dosage form by UV spectrophotometry

A simple, rapid and precise method was developed for the quantitative simultaneous determination of Omeprazole and Domperidone in combined pharmaceutical-dosage forms. The method was based on UV-Spectrophotometric determination of two drugs, using simultaneous equation method. It involves absorbance measurement at 291 nm (λmax of Omeprazole) and 289 nm (λmax of Domperidone) in Methanol: Acetonitrile (30:70 v/v). For UV Spectrophotometric method, linearity was obtained in concentration range of 1-15 µg/ml for Domperidone and 1-50 µg/ml for Omeprazole respectively, with regression 0.999 and 0.999 for Domperidone and Omeprazole respectively. Recovery was in the range of 99 -103%; the value of standard deviation and %R.S.D were found to be < 2 %; shows the high precision of the method., in accordance with ICH guidelines. The method has been successively applied to pharmaceutical formulation and was validated according to ICH guidelines