Phytochemicals as Inhibitors of Bacterial Cell Division Protein FtsZ: Coumarins Are Promising Candidates

Naturally occurring phytochemicals with reported antibacterial activity were screened for their ability to inhibit the bacterial cell division protein Escherichia coli FtsZ. Among the representative compounds, coumarins inhibit the GTPase and polymerization activities of this protein effectively. Further screening with ten coumarin analogs we identified two promising candidates, scopoletin and daphnetin. The former is found to inhibit the GTPase activity of the protein in a noncompetitive manner. Docking of these coumarins with the modeled protein indicate that they bind to T7 loop, which is different from the GTP-binding site (active site), thereby supporting the experimental data. Lowest binding energy is obtained with scopoletin. 3D QSAR indicates the need for groups such as hydroxyl, diethyl, or dimethyl amino in the 7th carbon for enhanced activity. None of the coumarins exhibited cytotoxicity against NIH/3T3 and human embryonic kidney cell lines. The length of Bacillus subtilis increases in the presence of these compounds probably due to the lack of septum formation. Results of this study indicate the role of coumarins in halting the first step of bacterial cell division process.     

Syntheses and characterization of a new class of vanadia precursors of oxime-modified oxovanadium(V) isopropoxide,crystal and molecular structure of [VO{ONC10H16}3]

Modification of [VO(OPrⁱ)₃] with oximes in different molar ratios, yielded new class of vanadia precursors, [VO{OPrⁱ}_3?n{L}_n] {where, n = 1–3 and LH = C₉H₁₆C=NOH (1–3) and (CH₃)₂C=NOH (4–6)}.All the products are yellow in colour. (1) and (2) are liquid/viscous liquid, while others are solids. Molecular weight measurements of all these derivatives and the ESI-mass spectral studies of (1), (2), (3) and (5) indicate their monomeric nature. ¹H and ¹³C{¹H} NMR spectra suggest that the oximato moieties are monodentate in solution which was further confirmed by the ⁵¹V NMR signals, appeared in the region expected for tetra-coordinated oxo-vanadium atoms. On ageing, a disproportionation reaction occurs in (1) and some crystals appeared. Single crystal X-ray diffraction analyses of the crystals obtained from (1) as well as from (3) were found to be the same and indicate the presence of side-on {dihapto η ²-(N, O)} binding modes of the oximato ligands, leading to the formation of seven coordination environment around the vanadium atom. Thermogravimetric curve of (1) exhibits multi-step decomposition with the formation of V₂O₅ as the final product at ~850 °C. Sol–gel transformation of (3) yielded (a) VO₂ sintered at 300 °C and (b) V₂O₅ at 600 °C. Similarly, sol–gel transformations of (1) and (2) yielded V₂O₅ (c) and (d) at 600 °C, respectively. Formation of monoclinic phase in (a) and orthorhombic phase in (b), (c) and (d) were confirmed by powder XRD patterns.     

Syntheses and characterization of a new class of zirconia precursors of oxime-modified zirconium(IV) isopropoxide

Some oxime modified complexes of the type [Zr{OPrⁱ}_4?n{L}_n] {where, n = 1–4 and LH=(CH₃)₂C=NOH (1–4) and C₉H₁₆C=NOH (5–8)} have been synthesized by the reaction of [Zr(OPrⁱ)₄·PrⁱOH] with oximes, in anhydrous refluxing benzene. These synthesized complexes were characterized by elemental analyses, molecular weight measurements, ESI-mass, FT-IR and NMR (¹H and ¹³C{¹H}) spectral studies. The ESI-mass spectral studies indicate dimeric nature for [Zr{OPrⁱ}₂{ONC(CH₃)₂}₂] (2), [Zr{OPrⁱ}₃{ONC₁₀H₁₆}] (5) and [Zr{OPrⁱ}{ONC₁₀H₁₆}₃] (7) and monomeric nature for [Zr{ONC₁₀H₁₆}₄] (8). Oximato ligands appear to bind the zirconium in side on manner in all the complexes. Thermogravimetric curves of (2) and (8) exhibit multi-step decomposition with the formation of ZrO₂, under nitrogen atmosphere. Sol–gel transformations of precursors (5), (6), (7) and (8) in organic medium, yielded nano-sized tetragonal phase of zirconia samples (a), (b), (c) and (d), respectively, on sintering at ~600 °C. All these samples were characterized by Powder XRD patterns and EDX analyses. Surface morphologies of these samples were investigated by SEM images.     

Target-Directed Azide-Alkyne Cycloaddition for Assembling HIV-1 TAR RNA Binding Ligands

The highly conserved HIV-1 transactivation response element (TAR) binds to the trans-activator protein Tat and facilitates viral replication in its latent state. The inhibition of Tat–TAR interactions by selectively targeting TAR RNA has been used as a strategy to develop potent antiviral agents. Therefore, HIV-1 TAR RNA represents a paradigmatic system for therapeutic intervention. Herein, we have employed biotin-tagged TAR RNA to assemble its own ligands from a pool of reactive azide and alkyne building blocks. To identify the binding sites and selectivity of the ligands, the in situ cycloaddition has been further performed using control nucleotide (TAR DNA and TAR RNA without bulge) templates. The hit triazole-linked thiazole peptidomimetic products have been isolated from the biotin-tagged target templates using streptavidin beads. The major triazole lead generated by the TAR RNA presumably binds in the bulge region, shows specificity for TAR RNA over TAR DNA, and inhibits Tat–TAR interactions.     

Tunable Surface Wrinkling by a Bio-Inspired Polyamine Anion Coacervation Process that Mediates the Assembly of Polyoxometalate Nanoclusters

A bio-inspired method is used to render controlled wrinkling surface patterns on supramolecular architectures assembled from polyoxometalate (POM) clusters. It involves a polyamine-multivalent anion interaction generating positively charged coacervates, which while dictating the assembly of POM into spherical structures further facilitate an interesting surface morphogenesis with wrinkling patterns. This spontaneous surface wrinkling depends on the type of multivalent anion and the pH. As the polyamine-anion interaction becomes stronger, the wrinkles turn denser with lesser depth, which eventually undergoes post-buckling to engender a complex surface pattern. Interestingly, the order of influence exerted by different anions on the morphology follows the Hofmeister series. Moreover, the mild synthesis conditions keep the functional POM units dispersed in the sphere with a structural transformability to their lacunary form.     

Synthesis,characterization, in silico and in vitro biological activity studies of Ru(II) (η6-p-cymene) complexes with novel N-dibenzosuberene substituted aroyl selenourea exhibiting Se type coordination

A series of N-dibenzosuberene substituted aroyl selenourea ligands L1–L3 and their Ru(II) (η⁶-p-cymene) complexes 1–3, [Ru(II) (η⁶-p-cymene) L] (L?=?monodentate aroyl selenourea ligand) were synthesized and characterized. The molecular structures of the ligand L3 and complex 3 were confirmed by single-crystal XRD method. The single-crystal XRD study results revealed that aroyl selenourea ligand coordinates with ruthenium via Se neutral monodentate atom. In vitro DNA interaction studies were investigated by UV–Visible and fluorescence spectroscopic methods which showed that the intercalative mode of binding is in the order of 3?>?2?>?1 with the Ru(II) (η⁶-p-cymene) complexes. The binding affinity of the bovine serum albumin with complexes was calculated using spectroscopic methods. Quantum chemical computations were made using DFT (density functional theory), BL3YP; LANL2DZ basis set in order to determine the frontier molecular orbital parameters and MESP for the newly synthesized complexes. The complexes 1–3 have shown intensive cytotoxicity against the cancer lines HepG-2 and A549 under in vitro conditions. Complex 3 (IC₅₀?=?62 μM) has shown significant cytotoxic activity against HepG-2 compared to cisplatin standard drug. The complexes also examined for their antimicrobial activity. The complex 2 exhibited good activity against B. subtilis (MIC: 13.60 μg/mL), E. coli (MIC: 8.01 μg/mL) and A. flavus (MIC?=?15.60 μg/mL), respectively, compared to reference drugs Streptomycin and Ketoconazole.

     

Production of Bioactive Compounds with Broad Spectrum Bactericidal Action,Bio-Film Inhibition and Antilarval Potential by the Secondary Metabolites of the Endophytic Fungus Cochliobolus sp. APS1 Isolated from the Indian Medicinal Herb Andrographis paniculata

Endophytes, being the co-evolution partners of green host plants, are factories of pharmaceutically valuable novel natural products. Cochliobolus sp. APS1, an endophyte of Andrographis paniculata (Green Chiretta), produces a plethora of natural bioactive compounds and the multipotent alkaloid Aziridine, 1-(2-aminoethyl)-, is the prime one among them. The isolate exhibited antibacterial, anti-biofilm, and antilarval potency. The MIC and MBC values of the ethyl-acetate culture extract ranged from 15.62 to 250 µg/mL against ten pathogenic microorganisms (including MRSA and VRSA). Killing kinetics data along with the leakage of macromolecules into the extracellular environment supports the cidal activity of the antibacterial principles. The broad spectrum antibacterial activity of Aziridine, 1-(2-aminoethyl)-, was optimized by a one-variable-at-a-time system coupled with response surface methodology, which led to a 45% enhancement of the antibacterial activity. The maximum response (22.81 ± 0.16 mm of zone of inhibition against MRSA) was marked in 250 mL Erlenmeyer flask containing 90 mL potato dextrose broth supplemented with (g%/L) glucose, 9.7; urea concentration, 0.74; with medium pH 6.48; after 8.76 days of incubation at 26 °C. APS1 strongly inhibited biofilm formation in the tested pathogenic microorganisms and acts as a larvicidal agent against the Dengue-vector Aedes aegypti. This is probably the first report of Aziridine, 1-(2-aminoethyl)-, from any endophytic source. Cochliobolus sp. APS1 possesses industrial importance for the production of bioactive alkaloids.     

Studies of magnetite nanoparticles synthesized by thermal decomposition of iron (III) acetylacetonate in tri(ethylene glycol)

In this paper, water-soluble magnetite nanoparticles have been directly synthesized by thermal decomposition of iron (III) acetylacetonate, Fe(acac)₃ in tri(ethyleneglycol). Size and morphology of the nanoparticles are determined by transmission electron microscopy (TEM) and dynamic light scattering (DLS) measurements while the crystal structure is identified using X-ray diffraction (XRD). Surface charge and surface coating of the nanoparticles are recognized using Fourier transform infrared spectroscopy (FTIR), X-ray photoelectron spectra (XPS) and zeta potential measurements. Magnetic properties are determined using vibrating sample magnetometer (VSM) and superconducting quantum interference device (SQUID) measurements. The results show that as-prepared magnetite nanoparticles are relatively monodisperse, single crystalline and superparamagnetic in nature with the blocking temperature at around 100 K. The magnetite nanoparticles are found to be highly soluble in water due to steric and electrostatic interactions between the particles arising by the surface adsorbed tri(ethyleneglycol) molecules and associated positive charges, respectively. Cytotoxicity studies on human cervical (SiHa), mouse melanoma (B16F10) and mouse primary fibroblast cells demonstrate that up to a dose of 80 μg/ml, the magnetic nanoparticles are nontoxic to the cells. Specific absorption rate (SAR) value has been calculated to be 885 and 539 W/gm for samples with the iron concentration of 1 and 0.5 mg/ml, respectively. The high SAR value upon exposure to 20 MHz radiofrequency signifies the applicability of as-prepared magnetite nanoparticles for a feasible magnetic hyperthermia treatment.