Molprint 2D-Based Identification and Synthesis of Novel Chromene Based Small Molecules that Target Pla2: Validation through Chemo-And Bioinformatics Approaches

Phospholipase A2 (PLA2) is known to regulate inflammation and hence it is considered as a validated drug-target by medicinal chemists. In this report, we have identified and considered a highly ranked ligand from the ZINC-drug-like compounds database that targets PLA2 via the MOLPRINT-2D based chemoinformatics drug-design approach. The computationally predicted lead molecule was found to contain a core moiety of a chromene ring, which is well known for its varied biological properties. Here, a novel and efficient retro-synthetic protocol for the synthesis of highly substituted chromene libraries was made. A one-pot synthesis of chromene was carried out using different aromatic primary alcohols, malononitrile and 4-hydroxy coumarin in the presence of a mild oxidant mixture called T3P®–DMSO, followed by a Suzuki coupling reaction to obtain the lead molecules. All of the tested compounds of the chromene series displayed inhibition of the venom PLA2 in the range of 12 to 68 μM. Among the tested compounds, 2-amino-4-(2′-methyl-[1,1′-biphenyl]-4-yl)-5-oxo-4,5-dihydropyrano[3,2-c]chromene-3-carbonitrile (7b) showed maximum inhibitory efficacy against venom PLA2 with an IC50 value of 12.5 μM. Furthermore, the designed PLA2 ligands bound to the active site of venom PLA2, whose binding affinity was comparable to nimesulide, indicating that the chromene moiety containing ligands could be novel lead-structures that serve as anti-inflammatory agents

EXPERIMENTAL WORK ON DIESEL ENGINE PERFORMANCE AND EMISSION CHARACTERISTICS USING NANO ADDITIVES IN DIESEL AND BIODIESEL

ABSTRACT Diesel engines are well adapted by mankind because of their low fuel consumption and better efficiency. In recent times researchers have focused more on alternate fuels, with the depleting trend of petro diesel. Biodiesel is the one of such alternate fuel whose calorific value nearer to diesel. Most of the researchers concluded that with the usage of biodiesels the emissions can be reduced maintaining the consistency in efficiency, compared to diesel. In the present era of Nano technology there is the scope to improve the efficiency of engines using Nano additives in blended fuels. In this work single cylinder 4 stroke DI diesel engine is selected. The performance of different blends of mahua oil methyl esters for which cerium oxide (CeO2) Nano additives of size 30-50 nm is added in different proportions in blended fuel. The experiment has been conducted with neat diesel fuel and diesel-biodiesel blends (addition of cerium oxide (CeO2) Nano additive) in a four stroke single cylinder direct injection (DI) diesel engine. Those results are compared with conventional diesel fuel, diesel-biodiesel blends showed good performance, lower carbon monoxide (CO), and hydro carbons(HC) but higher oxides of nitrogen (NOx) emission.

Heteroatom-synergistic effect on anchoring polysulfides In chalcone-linked nanographene covalent organic frameworks for high-performance Li─S batteries

Lithium-sulfur (Li─S) batteries are an attractive option for future energy storage devices because they offer higher theoretical specific capacity, energy density, and cost-effectiveness than commercial lithium-ion batteries. However, the practical applications of Li─S batteries are significantly limited by the shuttle effect caused by intermediate lithium polysulfides (LiPSs) and slow redox kinetics. In this study, the molecular engineering of chalcone-linked, sp2-bonded nanographene-type covalent organic frameworks (COFs) as sulfur hosts is reported to enhance interactions with LiPSs, thereby effectively suppressing the shuttle effect. The developed sulfur-hosting cathode material demonstrated outstanding battery performance, surpassing most reported materials by achieving a specific capacity of 1228 mA h g−1 at 0.5C, with 80% retention after 500 cycles and an average Coulombic Efficiency (C.E.) of 99%. Additionally, the mechanisms of sulfur immobilization, the subsequent conversion into lithium polysulfides (LiPSs), and their binding energies with COFs are investigated using density functional theory (DFT) calculations. These findings offer valuable insights into the structure-property relationships essential for developing more efficient sulfur-hosting cathodes

2-Methoxy-4-[3-(3-nitrophenyl)-4,5-dihydro-1H-pyrazol-5-yl]phenol

In the title compound, C16H15N3O4, the pyrazole ring has an envelope conformation, with the C atom substituted by the 2-methoxyphenol ring as the flap. Its mean plane makes dihedral angles of 56.78 (9) and 9.7 (1)° with the 2-methoxyphenol and 3-nitrophenyl rings, respectively. The benzene rings are inclined to one another by 49.37 (8)°. In the crystal, molecules are linked by pairs of O—H...N hydrogen bonds, forming inversion dimers with an R22(16) ring motif. The dimers are linked by C—H...O hydrogen bonds, forming slabs parallel to the ac plane. There are slipped parallel π–π interactions present within the slabs, involving inversion-related 2-methoxyphenol rings [intercentroid distance = 3.729 (1) Å] and inversion-related 3-nitrophenyl rings [intercentroid distance = 3.831 (1) Å]

N′-[(1E)-4-Hydroxy-3-Methoxybenzylidene]isonicotinohydrazide Monohydrate

In the title hydrate, C\sb 14H\sb 13N\sb 3O\sb 3⋅H\sb 2O, the dihedral angle between the pyridine and benzene rings is 2.52(9)\circ. Intra\-molecular O—-H⋅sO hydrogen bonds occur. In the crystal, O—-H⋅sO, O—-H⋅sN, N—-H⋅sO and C—-H⋅sO hydrogen bonds link the components into a three-dimensional network. π—π inter\-actions are also observed

Organic Field Effect Transistors Comprising Copolymers Synthesized without Structure-Directing Moieties with Enhanced Carrier Mobility

Conjugated materials are synthesized by C–C bond formation reactions. Trimethyltin and boronic acid are two widely used structure-directing moieties. While using the ethynyl moiety as a part of the monomer, additional structure-directing moieties are not needed. However, ethynylene will be part of the conjugated material. Often, the polymers with an ethynylene moiety negatively impact the polymers’ properties. However, the ethynylene moiety could minimize the dihedral angle if the monomer has steric functionalities. For example, BODIPY is an attractive monomer due to its high molar extinction coefficient, partial quinoidal character, and high quantum yield. However, materials based on BODIPY exhibited poor charge carrier mobility due to steric hindrance generated by four methyl groups. Herein, we copolymerize BODIPY with ethynylene comprising i-indigo and thieno-i-indigo. The copolymer with thieno-i-indigo showed increased molecular weight and significantly reduced band gap compared to the copolymer with i-indigo. The copolymer with i-indigo showed immeasurably low hole transport mobility. On the other hand, the copolymer with thieno-i-indigo exhibited 0.003 cm2V–1 s–1. These measurements were made using field effect transistors. We also measured the charge carrier mobility using the space charge-limited current method. Both copolymers exhibited a mobility of 10–3 cm2 V–1 s–1

N-substituted pyrido-1,4-Oxazin-3-ones induce apoptosis of hepatocellular carcinoma cells by targeting NF-κB signaling pathway

Hepatocellular carcinoma (HCC) is a fatal disease and ranked fifth in cancer related mortality. Persistent activation of NF-κB is responsible for the oncogenesis, metastasis, tumor evasion, anti-apoptosis, angiogenesis and proliferation in HCC. Therefore, designing of chemically novel, biologically potent small molecules that target NF-κB signaling cascade have gained prominent clinical interest. Herein we synthesized a novel class of 4-(substituted)-2H-pyrido[3,2-b][1,4]oxazin-3(4H)-one by reacting 2H-pyrido[3,2-b][1,4]oxazin-3(4H)-one with various alkyl halides by using combustion derived bismuth oxide. We evaluated the antiproliferative efficacy of newly synthesized compounds against HCC cells and identified 4-(4-nitrobenzyl)-2H-pyrido[3,2-b][1,4]oxazin-3(4H)-one (NPO) as lead anticancer agent. In addition, we investigated the effect of NPO on the DNA binding ability of NF-κB and NF-κB regulated luciferase expression in HCC cells. The results demonstrated that NPO can induce significant growth inhibitory effects in HepG2, HCCLM3 and Huh-7 cells in dose and time-dependent manner. Interestingly, NPO induced significant downregulation in p65 DNA binding ability, p65 phosphorylation and subsequent expression of NF-κB dependent luciferase gene expression in diverse HCC cell lines. Further, in silico docking analysis suggested that NPO can show direct physical interaction with NF-κB. Finally, NPO was found to significantly abrogate tumor growth at a dose of 50 mg/kg in an orthotopic mouse model. Thus, we report the potential anticancer effects of NPO as a novel inhibitor of NF-κB signaling pathway in HCC. Copyright © 2018 Mohan, Bharathkumar, Dukanya, Rangappa, Shanmugam