Synthesis, Molecular Docking Analysis and in Vitro Biological Evaluation of Some New Heterocyclic Scaffolds-Based Indole Moiety as Possible Antimicrobial Agents

In the present study, a general approach for the synthesis of 1-(1H-indol-3-yl)-3,3-dimercaptoprop-2-en-1-one (1) and 5-(1H-indol-3-yl)-3H-1,2-dithiole-3-thione (2) was performed. They are currently used as efficient precursors for the synthesis of some new compounds bearing five- and/or six-membered heterocyclic moieties, e.g., chromenol (3, 4), 3,4-dihydroquinoline (7, 8) and thiopyran (10, 12)-based indole core. In addition, molecular docking studies were achieved, which showed that all the newly synthesized compounds are interacting with the active site region of the target enzymes, the targets UDP-N-acetylmuramatel-alanine ligase (MurC), and human lanosterol14α-demethylase, through hydrogen bonds and pi-stacked interactions. Among these docked ligand molecules, the compound (9) was found to have the minimum binding energy (−11.5 and −8.5 Kcal/mol) as compared to the standard drug ampicillin (−8.0 and −8.1 Kcal/mol) against the target enzymes UDP-N-acetylmuramatel-alanine ligase (MurC), and Human lanosterol14α-demethylase, respectively. Subsequently, all new synthesized analogues were screened for their antibacterial activities against Gram-positive (Bacillus subtilis), and Gram-negative bacteria (Escherichia coli), as well as for antifungal activities against Candida albicans and Aspergillus flavus. The obtained data suggest that the compounds exhibited good to excellent activity against bacterial and fungi strains. The compound (E)-2-(6-(1H-indole-3-carbonyl)-5-thioxotetrahydrothieno [3,2-b]furan-2(3H)-ylidene)-3-(1H-indol-3-yl)-3-oxopropanedithioic acid (9) showed a high binding affinity as well as an excellent biological activity. Therefore, it could serve as the lead for further optimization and to arrive at potential antimicrobial agent.

Perovskite With Tunable Active-Sites Oxidation State by High-Valence W for Enhanced Oxygen Evolution Reaction

Perovskite oxides have been established as a promising kind of catalyst for alkaline oxygen evolution reactions (OER), because of their regulated non-precious metal components. However, the surface lattice is amorphous during the reaction, which gradually decreases the intrinsic activity and stability of catalysts. Herein, the precisely control tungsten atoms substituted perovskite oxides (Pr0.5Ba0.5Co1-xWxO3-δ) nanowires were developed by electrostatic spinning. The activity and Tafel slope were both dependent on the W content in a volcano-like fashion, and the optimized Pr0.5Ba0.5Co0.8W0.2O3-δ exhibits both excellent activity and superior stability compared with other reported perovskite oxides. Due to the outermost vacant orbitals of W6+, the electronic structure of cobalt sites could be efficiently optimized. Meanwhile, the stronger W-O bond could also significantly improve the stability of latticed oxide atoms to impede the generation of surface amorphous layers, which shows good application value in alkaline water splitting.

Silver nanoparticles embedded 2D g-C3N4 nanosheets toward excellent photocatalytic hydrogen evolution under visible light

Photocatalytic water splitting is considered to be a feasible method to replace traditional energy. However, most of the catalysts have unsatisfactory performance. In this work, we used a hydrothermal process to grow Ag nanoparticles in situ on g-C3N4 nanosheets, and then a high performance catalyst (Ag- g-C3N4) under visible light was obtained. The Ag nanoparticles obtained by this process are amorphous and exhibit excellent catalytic activity. At the same time, the local plasmon resonance effect of Ag can effectively enhance the absorption intensity of visible light by the catalyst. The hydrogen production rate promote to 1035 μmol g-1h-1 after loaded 0.6 wt% of Ag under the visible light, which was 313 times higher than that of pure g-C3N4 (3.3μmol g-1h-1). This hydrogen production rate is higher than most previously reported catalysts which loaded with Ag or Pt. The excellent activity of Ag- g-C3N4 is benefited from the Ag nanoparticles and special interaction in each other. Through various analysis and characterization methods, it is shown that the synergy between Ag and g-C3N4 can effectively promote the separation of carriers and the transfer of electrons. Our work proves that Ag- g-C3N4 is a promising catalyst to make full use of solar energy.

IrO2/LiLa2IrO6 as a Robust Electrocatalyst for Oxygen Evolution Reaction in Acidic Media

Recently reported non-noble metal-iridium mixed oxides not only exhibit excellent activity for the oxygen evolution reaction in acid media, but also reduce the cost. However, most of them fail to...

New Deoxycholic Acid Derived Tyrosyl-DNA Phosphodiesterase 1 Inhibitors Also Inhibit Tyrosyl-DNA Phosphodiesterase 2

A series of deoxycholic acid (DCA) amides containing benzyl ether groups on the steroid core were tested against the tyrosyl-DNA phosphodiesterase 1 (TDP1) and 2 (TDP2) enzymes. In addition, 1,2,4- and 1,3,4-oxadiazole derivatives were synthesized to study the linker influence between a para-bromophenyl moiety and the steroid scaffold. The DCA derivatives demonstrated promising inhibitory activity against TDP1 with IC50 in the submicromolar range. Furthermore, the amides and the 1,3,4-oxadiazole derivatives inhibited the TDP2 enzyme but at substantially higher concentration. Tryptamide 5 and para-bromoanilide 8 derivatives containing benzyloxy substituent at the C-3 position and non-substituted hydroxy group at C-12 on the DCA scaffold inhibited both TDP1 and TDP2 as well as enhanced the cytotoxicity of topotecan in non-toxic concentration in vitro. According to molecular modeling, ligand 5 is anchored into the catalytic pocket of TDP1 by one hydrogen bond to the backbone of Gly458 as well as by π–π stacking between the indolyl rings of the ligand and Tyr590, resulting in excellent activity. It can therefore be concluded that these derivatives contribute to the development of specific TDP1 and TDP2 inhibitors for adjuvant therapy against cancer in combination with topoisomerase poisons.

An amphipathic and cationic antimicrobial peptide kills colistin resistant Gram-negative pathogens in vivo

New antibiotics are needed against multidrug resistant Gram-negative pathogens that have compromised global health systems. Antimicrobial peptides are generally considered promising lead candidates for the next generation of antibiotics but have not fulfilled this expectation. Here we demonstrate activity of a cationic amphipathic undecapeptide (ChIP; Charge change Independent Peptide) against a wide panel of multidrug resistant Gram-negative pathogens. Importantly, the antimicrobial activity of ChIP is independent of the surface charge changes that confer colistin resistance through modification of Lipid A, while decreased activity of ChIP correlates with GlcN1 tri-acylation of Lipid A. In an in vivo peritonitis mouse model ChIP displays excellent activity against both colistin sensitive and resistant Escherichia coli and Acinetobacter baumannii strains.

Synthesis of highly stable dual-site immobilized ruthenium olefin metathesis catalyst without ru leaching

The tri-block copolymer is used as a carrier to simultaneously immobilize the N-heterocyclic and benzylidene ligands precursor of the Ru-based catalyst to form a dual-site immobilized catalyst. The dual-site immobilized catalyst can catalyze ring-opening metathesis polymerization, ring-closing metathesis and self-metathesis. The dual-site immobilized catalyst shows good heterogeneity in dichloromethane, which simplifies the purification of product and recovery of catalyst. The dual-site immobilized catalyst exhibits excellent activity and recycling performance. The excellent recyclability can be attributed to the capture of ruthenium by the excess ligands precursor on carrier. Importantly, ruthenium residues are not detected in product.