Efficient Synthesis of a Series of Novel Octahydroquinazoline-5-ones via a Simple on-Water Urea-Catalyzed Chemoselective Five-Component Reaction

Multicomponent reactions (MCRs) have become a powerful tool for drug discovery and development owing to their advantages of fast and efficient construction of a large library of products with complexity and diversity. However, conventional MCRs usually proceed in environmentally unfriendly organic solvents rather than in water, a green solvent used by nature for biological chemistry. Herein, a simple and efficient on-water urea-catalyzed chemoselective five-component reaction (5CR) has been developed for the synthesis of a series of novel octahydroquinazoline-5-ones (<b>6</b>), the derivatives of quinazolinones possessing diverse biological activities. The molecular structure of <b>6</b>{<i>1,1,12</i>} has been confirmed by single-crystal X-ray diffraction. The 5CR can proceed at room temperature under normal atmospheric pressure in good yields and afford a large library of octahydroquinazoline-5-ones with various aromatic and aliphatic substituents at N-1, C-2, and N-3. In addition, a green method has been developed for the synthesis of enaminones, important intermediates in the 5CR and in synthetic chemistry

Reduction of Nitric Oxide by Acetylene on Ir Surfaces with Different Morphologies: Comparison with Reduction of NO by CO

Reduction of nitric oxide (NO) by acetylene (C₂H₂) has been investigated by temperature-programmed desorption (TPD) on planar Ir(210) and faceted Ir(210) with tunable sizes of three-sided nanopyramids exposing (311), (311̅), and (110) faces. Upon adsorption, C₂H₂ dissociates to form acetylide (CCH) and H species on the Ir surfaces at low C₂H₂ precoverage. For adsorption of NO on C₂H₂-covered Ir, both planar and faceted Ir(210) exhibit high reactivity for reduction of NO with high selectivity to N₂ at low C₂H₂ precoverage, although the reaction is completely inhibited at high C₂H₂ precoverage. Coadsorbed C₂H₂ significantly influences dissociation of NO. The N-, H-, and C-containing TPD products are dominated by N₂, H₂, CO, and CO₂ together with small amounts of H₂O. For adsorption of NO on C-covered Ir(210) at fractional C precoverage, formation of CO₂ is promoted while production of CO is reduced. Reduction of NO by C₂H₂ is structure sensitive on faceted Ir(210) versus planar Ir(210), but no evidence is found for size effects in the reduction of NO by C₂H₂ on faceted Ir(210) for average facet sizes of 5 nm and 14 nm. The results are compared with reduction of NO by CO on the same Ir surfaces. As for NO+C₂H₂, the Ir surfaces are very active for reduction of NO by CO with high selectivity to N₂ and the reaction is structure sensitive, but clear evidence is found for size effects in the reduction of NO by CO on the nanometer scale. Furthermore, coadsorbed CO does not affect dissociation of NO at low CO precoverage whereas coadsorbed CO considerably influences dissociation of NO at high CO precoverage. The adsorption sites of CCH+H on Ir are characterized by density functional theory

Novel Terminal Bipheny-Based Diapophytoene Desaturases (CrtN) Inhibitors as Anti-MRSA/VISR/LRSA Agents with Reduced hERG Activity

CrtN has been identified as an attractive and druggable target for treating pigmented <i>Staphylococcus aureus</i> infections. More than 100 new compounds were synthesized, which target the overwhelming the defects of the CrtN inhibitor <b>1</b>. Analogues <b>23a</b> and <b>23b</b> demonstrated a significant activity against pigmented <i>S. aureus</i> Newman and 13 MRSA strains (IC₅₀ = 0.02–10.5 nM), along with lower hERG inhibition (IC₅₀ > 30 μM, ∼10-fold decrease in comparison with <b>1</b>). Furthermore, <b>23a</b> and <b>23b</b> were confirmed to reduce the staphylococcal load in the kidney and heart in a mouse model with normal treatment deeper than pretreatment ones, comparable even with vancomycin and linezolid. Remarkably, <b>23a</b> could strongly block the pigment biosynthesis of these nine multidrug-resistant MRSA strains, including excellent activity against LRSA strains and VISA strains in vivo, and all of which demonstrated that <b>23a</b> has a huge potential against intractable MRSA, VISA, and LRSA issues as a therapeutic drug

Novel Terminal Bipheny-Based Diapophytoene Desaturases (CrtN) Inhibitors as Anti-MRSA/VISR/LRSA Agents with Reduced hERG Activity

CrtN has been identified as an attractive and druggable target for treating pigmented <i>Staphylococcus aureus</i> infections. More than 100 new compounds were synthesized, which target the overwhelming the defects of the CrtN inhibitor <b>1</b>. Analogues <b>23a</b> and <b>23b</b> demonstrated a significant activity against pigmented <i>S. aureus</i> Newman and 13 MRSA strains (IC₅₀ = 0.02–10.5 nM), along with lower hERG inhibition (IC₅₀ > 30 μM, ∼10-fold decrease in comparison with <b>1</b>). Furthermore, <b>23a</b> and <b>23b</b> were confirmed to reduce the staphylococcal load in the kidney and heart in a mouse model with normal treatment deeper than pretreatment ones, comparable even with vancomycin and linezolid. Remarkably, <b>23a</b> could strongly block the pigment biosynthesis of these nine multidrug-resistant MRSA strains, including excellent activity against LRSA strains and VISA strains in vivo, and all of which demonstrated that <b>23a</b> has a huge potential against intractable MRSA, VISA, and LRSA issues as a therapeutic drug

Novel Inhibitors of Staphyloxanthin Virulence Factor in Comparison with Linezolid and Vancomycin versus Methicillin-Resistant, Linezolid-Resistant, and Vancomycin-Intermediate <i>Staphylococcus aureus</i> Infections in Vivo

Our previous work (Wang et al. J. Med. Chem. 2016, 59, 4831−4848) revealed that effective benzocycloalkane-derived staphyloxanthin inhibitors against methicillin-resistant <i>Staphylococcus aureus</i> (<i>S. aureus</i>) infections were accompanied by poor water solubility and high hERG inhibition and dosages (preadministration). In this study, 92 chroman and coumaran derivatives as novel inhibitors have been addressed for overcoming deficiencies above. Derivatives <b>69</b> and <b>105</b> displayed excellent pigment inhibitory activities and low hERG inhibition, along with improvement of solubility by salt type selection. The broad and significantly potent antibacterial spectra of <b>69</b> and <b>105</b> were displayed first with normal administration in the livers and hearts in mice against pigmented <i>S. aureus</i> Newman, Mu50 (vancomycin-intermediate <i>S. aureus</i>), and NRS271 (linezolid-resistant <i>S. aureus</i>), compared with linezolid and vancomycin. In summary, both <b>69</b> and <b>105</b> have the potential to be developed as good antibacterial candidates targeting virulence factors

Additional file 1 of GhIMP10D, an inositol monophosphates family gene, enhances ascorbic acid and antioxidant enzyme activities to confer alkaline tolerance in Gossypium hirsutum L.

Additional file 1: Supplementary Table S1. Gene locus ID and their proposed names of all observed species and the gene characteristics in G. hirsutum. Supplementary Table S2. Duplicated gene pairs in 10 combinations (Ga-Ga, Ga-Gb, Ga-Gr, Gb-Gb, Gb-Gr, Gh-Gh, Gh-Ga, Gh-Gb, Gh-Gr and Gr-Gr). Supplementary Table S3. Non-synonymous (Ka) and synonymous (Ks) divergence values for Ga-Ga, Ga-Gb, Ga-Gr, Gb-Gb, Gb-Gr, Gh-Gh, Gh-Ga, Gh-Gb, Gh-Gr and Gr-Gr. Supplementary Table S4. Primer pairs used for this experiment