1345853-50-0Relevant academic research and scientific papers
Identification of racemic and chiral carbazole derivatives containing an isopropanolamine linker as prospective surrogates against plant pathogenic bacteria: In vitro and in vivo assays and quantitative proteomics
Zhao, Yong-Liang,Huang, Xing,Liu, Li-Wei,Wang, Pei-Yi,Long, Qing-Su,Tao, Qing-Qing,Li, Zhong,Yang, Song
, p. 7512 - 7525 (2019)
Recent observations on the emergence of drug-resistant plant pathogenic bacteria have highlighted and elicited an acute campaign to develop novel, highly efficient antibiotic surrogates for managing bacterial diseases in agriculture. Thus, a type of racemic and chiral carbazole derivative containing an isopropanolamine pattern was systematically synthesized to discover low-cost and efficient antibacterial candidates. Screening results showed that compounds 2f, 6c, and 2j could significantly suppress the growth of tested plant pathogens, namely Xanthomonas oryzae pv oryzae, X. axonopodis pv citri, and Pseudomonas syringae pv actinidiae, and provided the corresponding EC50 values of 1.27, 0.993, and 0.603 μg/mL, which were significantly better than those of existing commercial drugs. In vivo studies confirmed their prospective applications for controlling plant bacterial diseases. Label-free quantitative proteomics analysis indicated that compound 2f could dramatically induce the up- and down-regulation of a total of 247 differentially expressed proteins, which was further validated by the parallel reaction monitoring technique. Moreover, fluorescence spectra and SEM images were obtained to further explore the antibacterial mechanism.
Sulfonamido-derivatives of unsubstituted carbazoles as BACE1 inhibitors
Bertini, Simone,Ghilardi, Elisa,Asso, Valentina,Minutolo, Filippo,Rapposelli, Simona,Digiacomo, Maria,Saccomanni, Giuseppe,Salmaso, Veronica,Sturlese, Mattia,Moro, Stefano,Macchia, Marco,Manera, Clementina
, p. 4812 - 4816 (2017/10/17)
A novel series of variously substituted N-[3-(9H-carbazol-9-yl)-2-hydroxypropyl]-arylsulfonamides has been synthesized and assayed for β-Secretase (BACE1) inhibitory activity. BACE1 is a widely recognized drug target for the prevention and treatment of Alzheimer's Disease (AD). The introduction of benzyl substituents on the nitrogen atom of the arylsulfonamide moiety has so far led to the best results, with three derivatives showing IC50 values ranging from 1.6 to 1.9 μM. Therefore, a significant improvement over the previously reported series of N-carboxamides (displaying IC50's ≥ 2.5 μM) has been achieved, thus suggesting an active role of the sulfonamido-portion in the inhibition process. Preliminary molecular modeling studies have been carried out to rationalize the observed structure-activity relationships.
Carbazole-containing arylcarboxamides as BACE1 inhibitors
Bertini, Simone,Asso, Valentina,Ghilardi, Elisa,Granchi, Carlotta,Manera, Clementina,Minutolo, Filippo,Saccomanni, Giuseppe,Bortolato, Andrea,Mason, Jonathan,Moro, Stefano,MacChia, Marco
, p. 6657 - 6661 (2011/12/04)
β-Secretase (BACE1) is widely recognized as a prime drug target for the treatment of Alzheimer's disease (AD). In this Letter, we report the synthesis and the BACE1 inhibitory activity of novel, variously substituted N-[3-(9H-carbazol-9-yl)-2-hydroxypropyl]-arylcarboxamides. The best results have been obtained with the introduction of a 4-OMe substituent (IC50 = 3.8 μM) or a 3,4-dichloro substituent (IC50 = 2.5 μM) in the amidic aromatic ring. The blood-brain barrier penetration predictions resulted to be promising for this type of compounds. To better understand the structure-activity relationships (SAR) of the new derivatives, a docking study procedure has been applied exploiting different conformational and ionic states of BACE1.
