In Silico Prediction,Molecular Docking and Dynamics Studies of Steroidal Alkaloids of Holarrhena pubescens Wall. ex G. Don to Guanylyl Cyclase C: Implications in Designing of Novel Antidiarrheal Therapeutic Strategies

The binding of heat stable enterotoxin (STa) secreted by enterotoxigenic Escherichia coli (ETEC) to the extracellular domain of guanylyl cyclase c (ECD_GC-C) causes activation of a signaling cascade, which ultimately results in watery diarrhea. We carried out this study with the objective of finding ligands that would interfere with the binding of STa on ECD_GC-C. With this view in mind, we tested the biological activity of a alkaloid rich fraction of Holarrhena pubescens against ETEC under in vitro conditions. Since this fraction showed significant antibacterial activity against ETEC, we decided to test the screen binding affinity of nine compounds of steroidal alkaloid type from Holarrhena pubescens against extracellular domain (ECD) by molecular docking and identified three compounds with significant binding energy. Molecular dynamics simulations were performed for all the three lead compounds to establish the stability of their interaction with the target protein. Pharmacokinetics and toxicity profiling of these leads demonstrated that they possessed good drug-like properties. Furthermore, the ability of these leads to inhibit the binding of STa to ECD was evaluated. This was first done by identifying amino acid residues of ECD_GC-C binding to STa by protein–protein docking. The results were matched with our molecular docking results. We report here that holadysenterine, one of the lead compounds that showed a strong affinity for the amino acid residues on ECD_GC-C, also binds to STa. This suggests that holadysenterine has the potential to inhibit binding of STa on ECD and can be considered for future study, involving its validation through in vitro assays and animal model studies.     

Synthesis,Structures, and Fungitoxicity of Novel Organophosphorus Compounds

Abstract

A series of biologically active organophosphorus compounds have been synthesized by the reactions of O,O-diethylchlorophosphate with Schiff bases derived from 5-(phenyl/substituted phenyl)-2-hydrazino-1,3,4-oxadiazole and salicylaldehyde/2-hydroxyacetophenone. The compounds have been characterized on the basis of analyses and spectral (IR, ¹H, ¹³C NMR) data. Fungicidal activities of these derivatives against Colletotrichum falcatum, Fusarium oxysporum, and Curvularia pallescence have been evaluated. All compounds showed moderate to significant antifungal activity.     

Synthesis,Structural, and Antibacterial Studies of Some Mixed Ligand Complexes of Zn(II), Cd(II), and Hg(II) Derived From Citral Thiosemicarbazone and N-Phthaloyl Amino Acids

A series of new mixed ligand complexes of Zn(II), Cd(II), and Hg(II) with cis-3,7-dimethyl-2,6-octadienthiosemicarbazone (CDOTSC; LH) and N-phthaloyl amino acids (AH) have been synthesized by the reaction of metal dichloride with ligands CDOTSC and N-phthaloyl derivative of DL-glycine (A₁H), L-alanine (A₂H), or L-valine (A₃H) in a 1:1:1 molar ratio in dry refluxing ethanol. All the isolated complexes have the general composition [M(L)(A)]. The plausible structure of these newly synthesized complexes has been proposed on the basis of elemental analyses, molar conductances, molecular weight measurement, and various spectral (IR, ¹H NMR, and ¹³C NMR) studies, and four coordinated geometries have been assigned to these complexes. All the complexes and ligands have been screened for their antibacterial activity.     

Morphology of solution crystallized trans-1,4-polyisoprene

The film formation method has been successfully used to grow single crystals and other complex morphological features of low melting form (LMF) and high melting form (HMF) of trans-1,4-polyisoprene (TPIP). Below 40 °C dilute amyl acetate solution gave hexagonal shaped LMF crystals. Thick and elongated hexagonal shaped morphology was shown by HMF crystals at temperatures above 40 °C. Straight faces and sharp corners of the single crystals, and also of complex crystals, acquired round shapes when highly polydispersed TPIP was used for crystallization.     

Spectrophotometric Label-Free Determination of Lead Using Thiol-Functionalized Gold Nanoparticles

A method for the determination of lead is described using thiol-functionalized gold nanoparticle. The detection method is based on the prevention of thiol-induced aggregation of gold nanoparticles by lead. Among six thiols, e.g., 4-mercapto-1-butanol, meso-2, 3-dimercaptosuccinic acid, mercaptosuccinic acid, 6-mercapto-1-hexanol, 4-(methylthio)-1-butanol, 1-propanethiol, four (4-mercapto-1-butanol, 6-mercapto-1-hexanol, 4-(methylthio)-1-butanol and 1-propanethiol) induced the aggregation of the gold nanoparticles which was measured by the change in absorbance at 520 and 650?nm. Prior incubation of the gold nanoparticles with lead decreased the 4-(methylthio)-1-butanol-induced aggregation of gold nanoparticles in a dose-dependent manner. A linear inverse relationship between the logarithmic concentration of lead and the ratio of absorbance at 650 to 520 was noted. The method has a dynamic range from 10?nM to 100?µM. However, metals such as mercury and chromium were more effective in comparison with lead in preventing the 4-methylthio-1-butanol-induced aggregation of gold nanoparticles. The method can be used for assessing the heavy metal load in water samples.     

Effect of bovine serum albumin on the surface properties of ionic liquid-type Gemini surfactant

The effect of bovine serum albumin on the surface properties of IL-type gemini surfactant ([C₁₀-4-C₁₀im]Br₂), have been investigated by surface tension method. The critical micelle concentration (CMC) as a function of BSA concentrations at various temperatures was investigated. The CMC of [C₁₀-4-C₁₀im]Br₂ increases with increasing the concentration of BSA as well as the temperature of the system. The interfacial parameters viz; maximum surface excess concentration (Γ_max), the minimum area per molecule (A_min), and surface pressure at CMC (Π_cmc) were calculated. In addition, thermodynamic parameters of adsorption and micellization were evaluated by using surface tension data. The results indicated that the binding of [C₁₀-4-C₁₀im]Br₂ to BSA is spontaneous and exothermic in nature. The process is entropy driven and hydrophobic interactions are the major driving forces.     

One pot three component synthesis of spiro [indolo-3,10’-indeno[1,2-b]quinolin]-2,4,11’-triones as a new class of antifungal and antimicrobial agents

A simple and efficient three component procedure has been developed for the synthesis of highly substituted spiro[indolo-3,10'-indeno[1,2-b]quinolin]-2,4,11'-triones by one pot three component condensation of enaminones, isatin and indane-1,3-dione in ethanol:water (1:1) in presence of ceric ammonium nitrate (CAN) as catalyst. This method provides several advantages such as lesser reaction time, high yield of products and operational simplicity. The antimicrobial activity of some of the compounds has been investigated against six microbial strains, some of the tested compounds showed good antimicrobial activity.     

The sampling theorem and coherent state systems

The Poisson Summation Formula and the sampling theorem for band limited signals, well known in the context of Fourier transformation theory, are analyzed from the perspective of the Zak basis and coherent state systems associated with the Heisenberg-Weyl group. In particular, we rephrase the content of the sampling theorem in terms coherent states and show that this in turn permits extensions, which allow us to make specific statements concerning standard and generalized coherent state systems on von Neumann or finer lattices. The text was submitted by the author in English.