Docking-based virtual screening of known drugs against murE of Mycobacterium tuberculosis towards repurposing for TB.

Repurposing has gained momentum globally and become an alternative avenue for drug discovery because of its better success rate, and reduced cost, time and issues related to safety than the conventional drug discovery process. Several drugs have already been successfully repurposed for other clinical conditions including drug resistant tuberculosis (DR-TB). Though TB can be cured completely with the use of currently available anti-tubercular drugs, emergence of drug resistant strains of Mycobacterium tuberculosis and the huge death toll globally, together necessitate urgently newer and effective drugs for TB. Therefore, we performed virtual screening of 1554 FDA approved drugs against murE, which is essential for peptidoglycan biosynthesis of M. tuberculosis. We used Glide and AutoDock Vina for virtual screening and applied rigid docking algorithm followed by induced fit docking algorithm in order to enhance the quality of the docking prediction and to prioritize drugs for repurposing. We found 17 drugs binding strongly with murE and three of them, namely, lymecycline, acarbose and desmopressin were consistently present within top 10 ranks by both Glide and AutoDock Vina in the induced fit docking algorithm, which strongly indicates that these three drugs are potential candidates for further studies towards repurposing for TB

Liquid/Single Crystal Structure Analysis: Synthesis and Characterization of a Trimethylsilyl Derived Rod Shaped Mesogen

4-[4’-Cyanophenoxy-carbonyl-phenyl-4-(trimethylsilyl)ethynyl]benzoate a rod shaped liquid crystal (SmA) is synthesized and characterized. The single-crystals were grown in triclinic crystal system in the space group of Pi - with unit cell parameters a = 5.9577(2) Å, b = 8.0398(3) Å, c = 25.8842(9) Å, a = 86.096(2)o , ß = 89.912(2)o , ? = 2.919(2)o , Z = 2, and V = 1182.16(7). The crystal structure is stabilized by C–H···O intra-molecular interactions. Further, the structure also involves C–H···p interactions and weak p–p stacking interactions [centroid–centroid separation = 3.806 (3) Å

GAS CHROMATOGRAPHY MASS SPECTROMETRY (GC-MS) ANALYSIS AND DOCKING STUDIES OF ANDROGRAPHIS PANICULATA AGAINST DENGUE FEVER

Objective: To evaluate gas chromatography- mass spectrometry (GC-MS) analysis and molecular docking studies of ethanol extract of Andrographis paniculata (Burm.f.) against type 2 dengue virus (DEN2).Methods: The ethanol extract of A. paniculata compounds were identified by GC-MS analysis. These compounds were further analysed for their activities against NS2B/NS3 protease of DEN2 by molecular docking studies. Results: The nine compounds obtained from the ethanol extract of A. paniculata were characterized and docked. Among these nine compounds, Vor-diazepam,3-[[N-hydroxymethyl]aminocarbonyloxy], Dasycarpidan-1-methanol, acetate (ester), Ethanol, 2-(9, 12-octadecadienyloxy)-, (Z, Z), Gibb-2-ene-1,10-dicarboxylicacid4a,7-dihydroxy-1-methylene-1,4a-lactone,10 methylester, (1a,4aa,4ba,10a) were found to show better interaction energetically and also showed crucial interactions with the active site of NS2B/NS3 protease. Thus A. paniculata is suggested to be a medicinally important plant to cure dengue fever.Conclusions: From the result, it can be concluded that the crude extract of A. paniculata compounds positively inhibit the activities of NS2B/NSB protease of DEN2 thus by preventing the dengue viral infection. This strategy reflects a logical progression for an early stage drug discovery which can be used to identify new drug candidates.Â

3D-QSAR studies on fluroquinolones derivatives as inhibitors for tuberculosis

A quantitative structure activity relationship (QSAR) study was performed on the fluroquinolones known to have anti-tuberculosis activity. The 3D-QSAR models were generated using stepwise variable selection of the four methods - multiple regression (MR), partial least square regression (PLSR), principal component regression (PCR) and artificial neural networks (kNN-MFA). The statistical result showed a significant correlation coefficient q2 (90%) for MR model and an external test set of (pred_r2) -1.7535, though the external predictivity showed to improve using kNN-MFA method with pred_r2 of -0.4644. Contour maps showed that steric effects dominantly determine the binding affinities. The QSAR models may lead to a better understanding of the structural requirements of anti-tuberculosis compounds and also help in the design of novel molecules

8,13,26-Trioxa-23-thia-21-azapentacyclo[18.6.0.0^2,7.0^14,19.0^21,25]hexacosa-2(7),3,5,14,16,18-hexaene

In the title compound, C(21)H(23)NO(3)S, both the thia­zole and oxazolidine rings adopt twist conformations. The mean plane of the thia­zole ring makes a dihedral angle of 61.02 (7)° with the oxazolidine ring mean plane, and dihedral angles of 22.72 (6) and 75.07 (6)° with the benzene rings. The benzene rings are almost perpendicular to one another, making a dihedral angle of 89.14 (6)°. There are bifurcated intra­molecular C—H⋯O hydrogen bonds in the mol­ecular structure. In the crystal, mol­ecules are linked via C—H⋯π inter­actions, forming chains propagating along [100]

A novel discrete dinuclear copper(II)–gadolinium(III) complex derived from a Schiff base ligand [Cu(salbn)Gd(NO 3 ) 3 ·H 2 O] (salbn): N , N ′-butylenebis(salicylideaminato)

The synthesis, X-ray and e.p.r. spectral studies of a 3d–4f couple are described here. The crystal structure of [Cu(salbn)Gd(NO 3 ) 3 ·H 2 O], (2) , salbn = N , N ′-butylenebis(salicylideaminato), has been determined by X-ray crystallography. Compound (2) crystallizes in the monoclinic system, space group p21/n, with a = 9.025(1), b = 22.912(1), c = 12.790(1) Å, β = 99.36(1), Z = 4. The deviations of the four coordinating atoms (O(1)O(2)N(1) and N(2) of salbn and the copper atom is displaced from the plane in spite of the lack of any apical ligand. The gadolinium(III) ion is nine-coordinated by the two oxygen atoms of the salbn moiety, three bidentate nitrate ions and one water molecule. The geometry of Gd III can be described as a square antiprism, in which compound Cu II and Gd III are bridged by the two phenolic oxygens of salbn. The Cu II –Gd III distance is 3.269(1) Å. The bridging core CuO2Gd is a butterfly shape. Significant distortion was observed for the complex having the larger diamino string. The title compound exhibits seven e.s.r. transitions with | D | = 0.0467 cm −1 , which demonstrates the existence of zero field splitting. This outcome indicates that compound (2) consists of a perfectly isolated dinuclear Cu–Gd core and steric bulk alters the dihedral angle in the Cu–O–Gd bridge.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/43854/1/11243_2004_Article_5115383.pd