Total Synthesis of the Natural Product Benzo[<i>j</i>]fluoranthene-4,9-diol: An Approach to the Synthesis of Oxygenated Benzo[<i>j</i>]fluoranthenes

A synthetic sequence to the benzo­[<i>j</i>]­fluoranthene nucleus is described. Crucial steps of the procedure include a Suzuki coupling between appropriately substituted 2-bromo-acenaphthylene-1-carbaldehydes and 2-formylbenzeneboronates followed by McMurry ring closure. The synthesis represents a new approach to the benzo­[<i>j</i>]­fluoranthene ring system and specifically provides a method for the rapid preparation of differently substituted derivatives. Following this strategy, the first total synthesis of the recently isolated natural product benzo­[<i>j</i>]­fluoranthene-4,9-diol was carried out

Stilbenoids as Antifungals to Counteract Rice Blast Pathogen Pyricularia oryzae

Fungi are among the greatest biotic threats to agricultural and food security. Intensive monoculture cropping and resistance to single-site fungicides in plant pathogens urge the discovery and development of novel compounds that possibly interfere with essential cellular processes in multiple ways. In this article, we describe our recent efforts addressed to the identification of natural compounds as multitarget biofungicides. A set of natural monomeric and dimeric compounds belonging to the class of stilbenoids were synthesized and tested against wild-type (WT) and strobilurin-resistant (RES) strains of Pyricularia oryzae, one of the most dangerous fungal phytopathogens. Monomers deoxyrhapontigenin, pinostilbene, and DMHS showed inhibitory activity higher than 40%, with deoxyrhapontigenin having the highest activity on mycelial growth (60–80% inhibition) on both WT and RES P. oryzae strains. Furthermore, we designed and synthesized a set of molecules having a nature-derived stilbene fragment merged with the pharmacophoric portion of strobilurins, namely, a β-methoxyacrylate moiety. We identified two molecules with activity comparable to the reference commercial fungicide azoxystrobin. However, low mycelium growth inhibition of resistant strains indicates that these compounds most likely retain the strobilurin-like mechanism of action. Overall, the results suggest that natural stilbenoids might be used as environmentally friendly biofungicides in rice blast management

Promysalin is a salicylate-containing antimicrobial with a cell-membrane-disrupting mechanism of action on Gram-positive bacteria.

Promysalin was previously described as a narrow spectrum molecule with a unique species-specific activity against Pseudomonas aeruginosa. Here we demonstrate that promysalin is active against Gram-positive and Gram-negative bacteria using a microdilution assay. Promysalin acts on Gram-positive bacteria with a mechanism of action involving cell membrane damage with leakage of intracellular components. The evaluation of MICs and MBCs on 11 promysalin analogs, synthesized utilizing diverted total synthesis, allowed the identification of the structural moieties potentially involved in cell membrane interaction and damage. The mechanism of action of promysalin against Gram-negative bacteria is still not clarified, even if a synergistic effect with the bisguanidine chlorhexidine on cell membrane disruption has been observed

Polyindole-ZnO Nanocomposite: Synthesis, Characterization and Heterogeneous Catalyst for the 3,4-Dihydropyrimidinone Synthesis under Solvent-free Conditions

<div><p>A Polyindole-ZnO nanocomposite particle was synthesized by using a chemical oxidative polymerization method. Synthesized nanocomposite was characterized by UV-Visible, FTIR, SEM, XRD, EDAX and electrical conductivity measurements. The band at ∼3400 cm⁻¹ and 735 cm⁻¹ in FTIR spectra confirmed the polyindole formation. XRD spectral studies exhibits major diffraction in between 30–40° (2θ) indicates the partial crystalline nature of the polyindole-ZnO nanocomposite. SEM image reveals agglomerated granular particulate nature with ZnO embedded in the polyindole matrix. The application of Polyindole-ZnO nanocomposite as a polymer-supported catalyst was studied for the synthesis of one pot multicomponent Biginelli condensation.</p> </div

Primary screening identifies compounds capable of inducing FOXO translocation.

<p>(A) U2fox RELOC cells were treated either with DMSO, 4nM LMB, 10μM of compound LOM 612 or compound LOM 621 for 30 min. representative images are shown. (B) Dose-response relationship of the nuclear–cytoplasmic shuttling of FOXO following LOM 612 treatment. LOM612 induces nuclear translocation in a dose dependent manner. Represented is the percentage of cells with more GFP fluorescence accumulation in nucleus than in cytoplasm. Results represent the mean of three independent experiments.</p

LOM612 compromises the viability of human cancer cell lines.

<p>(A) Breast cancer cell line MCF7, melanoma cell line A2058 and the neuroblastoma cell line SH-SY5 were seeded at a concentration of 1× 10⁴ cells/well in 200 μl and treated with compounds LOM612 and LOM621 for 72 hours with eight 2-fold serial dilutions of each compound spanning concentrations from 50μM to 0.39μM. Data is shown as mean ± SEM of three independent experiments. ****<i>P</i><0.0001 by two-way ANOVA (ns, not significant). (B) Human liver cancer cell lines HepG2 and THLE-2 (cell line derived from primary normal liver epithelial cells) were seeded at a concentration of 1× 10⁴ cells/well in 200 μl and treated with 20 different concentrations of LOM612 from 50μM to 95pM. Data is shown as mean ± SEM of three independent experiments. ****<i>P</i><0.0001 by two-way ANOVA.</p

Synthesis of compounds 1a-c (LOM612/621/604).

<p>(a) chlorocarbonylsulphenyl chloride, <i>N</i>, <i>N</i>-dimethylurea or <i>N</i>,<i>N</i>-dibenzylurea, acetonitrile, 2h RT for <b>3a</b>: 84%, <b>3b</b>: 62%; chlorocarbonylsulphenyl chloride, benzamide, toluene, 3h, reflux <b>3c</b>: 70%; (b) 1,4-naftochinone, <b>3a</b>, xilene, 80°C, 3h, 23%; 1,4-naftochinone, <b>3b</b>, xylene, 80°C, 3h, 63%; (C) 1,4-naftochinone, <b>3c</b>, xilene, 8h, reflux, 3h, 38%; d) CAN, CH₃CN: H₂O 9:1, 1h, RT, 89%.</p

LOM612 specifically induces the nuclear translocation of endogenous FOXO proteins.

<p>(A) Compound LOM612 induces the nuclear translocation of endogenous FOXO3a and FOXO1 protein detected by using a specific antibodies after 30 min of drug exposure. (B) LOM612 does not inhibit the nuclear export. U2OS cells stably expressing nuclear export signal (NES) (Rev-NES-EGFP) reporter were treated with DMSO, LMB, LOM612 and LOM621 for 30 min. (C) LOM612 does not induce nuclear translocation of endogenous nuclear factor (NF)–κB2 protein. Representative images of the compound-treated cells using a Leica SPE confocal imaging system. Cells were seeded automatically at appropriate density in 96-well black-wall clear-bottom tissue culture plates and allowed to attach overnight. Cells were then treated with compounds for 30 min before paraformaldehyde (Rev-NES-EGFP) or methanol (FOXO3a, NFKB2) fixation and DAPI staining.</p