3943-91-7Relevant articles and documents
Synthesis and SAR of 2,3-Dihydro-1-benzofuran-4-carboxylates: Potent Salicylic Acid-Based Lead Structures against Plant Stress
Bojack, Guido,Brown, Ronald W.,Dittgen, Jan,Heinemann, Ines,Helmke, Hendrik,Hills, Martin J.,Hohmann, Sabine,Holstein, Philipp M.,Schmutzler, Dirk,Frackenpohl, Jens
, (2022/03/27)
New 2,3-dihydro-1-benzofuran-4-carboxylic acid derivatives have been identified as potent lead structures against drought and cold stress in crops starting from the synthetic exploration of stabilized analogs of the natural product lunularic acid. An optimized Lewis-acid mediated cyclization gave a short and efficient access to the envisaged 2,3-dihydro-1-benzofuran-4-carboxylates. Enantioselective approaches were investigated to assess the potential impact of the chiral center on in vivo activity. Whilst 2,3-dihydro-1-benzofuran-4-carboxamides and 2,3-dihydro-1-benzofuran-4-carboxylates carrying phenyl substituents with electron-withdrawing groups exhibited only low to moderate in vivo activity, the corresponding 2,3-dihydro-1-benzofuran-4-carboxylates carrying optimized electron-donating substituents in the phenyl moiety revealed strong in vivo activity, both against drought stress in several broad-acre crops, as well as against cold stress in corn. Remarkably, several 2,3-dihydro-1-benzofuran-4-carboxylates showed stronger efficacy than the internal standards used in our in vivo SAR study.
Design of antibacterial agents: Alkyl dihydroxybenzoates against xanthomonas citri subsp. citri
Nazaré, Ana Carolina,Polaquini, Carlos Roberto,Anselmo, Daiane Bertholin,Regasini, Luis Octavio,Cavalca, Lúcia Bonci,Ferreira, Henrique,Zielinska, Aleksandra,Scheffers, Dirk-Jan,Saiki, Marilia de Freitas Calmon,Monteiro, Diego Alves,Rahal, Paula,Gomes, Eleni
, (2018/11/21)
Xanthomonas citri subsp. citri (Xcc) causes citrus canker, affecting sweet orange-producing areas around the world. The current chemical treatment available for this disease is based on cupric compounds. For this reason, the objective of this study was to design antibacterial agents. In order to do this, we analyzed the anti-Xcc activity of 36 alkyl dihydroxybenzoates and we found 14 active compounds. Among them, three esters with the lowest minimum inhibitory concentration values were selected; compounds 4 (52 μM), 16 (80 μM) and 28 (88 μM). Our study demonstrated that alkyl dihydroxybenzoates cause a delay in the exponential phase. The permeability capacity of alkyl dihydroxybenzoates in a quarter of MIC was compared to nisin (positive control). Compound 28 was the most effective (93.8), compared to compound 16 (41.3) and compound 4 (13.9) by percentage values. Finally, all three compounds showed inhibition of FtsZ GTPase activity, and promoted changes in protofilaments, leading to depolymerization, which prevents bacterial cell division. In conclusion, heptyl dihydroxybenzoates (compounds 4, 16 and 28) are promising anti-Xcc agents which may serve as an alternative for the control of citrus canker.
1,2,4-Triazole-3-thione Compounds as Inhibitors of Dizinc Metallo-β-lactamases
Sevaille, Laurent,Gavara, Laurent,Bebrone, Carine,De Luca, Filomena,Nauton, Lionel,Achard, Maud,Mercuri, Paola,Tanfoni, Silvia,Borgianni, Luisa,Guyon, Carole,Lonjon, Pauline,Turan-Zitouni, Gülhan,Dzieciolowski, Julia,Becker, Katja,Bénard, Lionel,Condon, Ciaran,Maillard, Ludovic,Martinez, Jean,Frère, Jean-Marie,Dideberg, Otto,Galleni, Moreno,Docquier, Jean-Denis,Hernandez, Jean-Fran?ois
, p. 972 - 985 (2017/06/27)
Metallo-β-lactamases (MBLs) cause resistance of Gram-negative bacteria to β-lactam antibiotics and are of serious concern, because they can inactivate the last-resort carbapenems and because MBL inhibitors of clinical value are still lacking. We previously identified the original binding mode of 4-amino-2,4-dihydro-5-(2-methylphenyl)-3H-1,2,4-triazole-3-thione (compound IIIA) within the dizinc active site of the L1 MBL. Herein we present the crystallographic structure of a complex of L1 with the corresponding non-amino compound IIIB (1,2-dihydro-5-(2-methylphenyl)-3H-1,2,4-triazole-3-thione). Unexpectedly, the binding mode of IIIB was similar but reverse to that of IIIA. The 3 D structures suggested that the triazole–thione scaffold was suitable to bind to the catalytic site of dizinc metalloenzymes. On the basis of these results, we synthesized 54 analogues of IIIA or IIIB. Nineteen showed IC50 values in the micromolar range toward at least one of five representative MBLs (i.e., L1, VIM-4, VIM-2, NDM-1, and IMP-1). Five of these exhibited a significant inhibition of at least four enzymes, including NDM-1, VIM-2, and IMP-1. Active compounds mainly featured either halogen or bulky bicyclic aryl substituents. Finally, some compounds were also tested on several microbial dinuclear zinc-dependent hydrolases belonging to the MBL-fold superfamily (i.e., endonucleases and glyoxalase II) to explore their activity toward structurally similar but functionally distinct enzymes. Whereas the bacterial tRNases were not inhibited, the best IC50 values toward plasmodial glyoxalase II were in the 10 μm range.
