623-33-6Relevant articles and documents
Construction and Evaluation of Molecular Models: Guide and Design of Novel SE Inhibitors
An, Yunfei,Dong, Yue,Han, Jun,Min, Liu,Sun, Bin,Zhao, Dongmei,Zhao, Liyu
, p. 1152 - 1159 (2020)
Squalene epoxidase (SE) was considered an important antifungal target to block ergosterol synthesis. In this study, molecular models of CASE including the homology model and the SBP were constructed, respectively. Three representative SE inhibitors were selected and docked into the active site of CASE. Subsequently, the novel SE inhibitors were designed based on the analysis of the inhibitor binding mode and the distribution of pharmacophore features. These compounds were further synthesized and tested in vitro. They exhibited a certain degree of antifungal activity, especially compound 7a-2, which also has a significant inhibitory effect on resistant fungi. Further analysis found that compound 7a-2 could inhibit SE, which is similar to naftifine. The study proved the rationality of the molecular models; they can help us design and discover more potent antifungal SE inhibitors.
Dispirooxindoles based on 2-selenoxo-imidazolidin-4-ones: Synthesis, cytotoxicity and ros generation ability
Novotortsev, Vladimir K.,Kukushkin, Maxim E.,Tafeenko, Viktor A.,Skvortsov, Dmitry A.,Kalinina, Marina A.,Timoshenko, Roman V.,Chmelyuk, Nelly S.,Vasilyeva, Liliya A.,Tarasevich, Boris N.,Gorelkin, Petr V.,Erofeev, Alexander S.,Majouga, Alexander G.,Zyk, Nikolai V.,Beloglazkina, Elena K.
, p. 1 - 26 (2021/03/09)
A regio-and diastereoselective synthesis of two types of dispiro derivatives of 2-selenoxoim-idazolidin-4-ones, differing in the position of the nitrogen atom in the central pyrrolidine ring of the spiro-fused system—namely, 2-selenoxodispiro[imidazolidine-4,3′-pyrrolidine-2′,3′′-indoline]-2′′, 5-diones (5a-h) and 2-senenoxodispiro[imidazolidine-4,3′-pyrrolidine-4′,3′′-indoline]-2′′,5-diones (6a-m)—were developed based on a 1,3-dipolar cycloaddition of azomethine ylides generated from isatin and sarcosine or formaldehyde and sarcosine to 5-arylidene or 5-indolidene-2-selenoxo-tetrahydro-4H-imidazole-4-ones. Selenium-containing dispiro indolinones generally exhibit cytotoxic activity near to the activity of the corresponding oxygen and sulfur-containing derivatives. Compounds 5b, 5c, and 5e demonstrated considerable in vitro cytotoxicity in the 3-(4,5-dimethylthiazol-2-yl)2,5-diphenyl tetrazolium bromide (MTT) test (concentration of compounds that caused 50% death of cells (CC50) 7.6–8.7 μM) against the A549 cancer cell line with the VA13/A549 selectivity index 5.2– 6.9 and compound 6e—against the MCF7 cancer cell line (CC50 20.6 μM, HEK293T/A549 selectivity index 1.6); some compounds (5 and 6) increased the level of intracellular reactive oxygen species (ROS) in the experiment on A549 and PC3 cells using platinized carbon nanoelectrode. The tests for p53 activation for compounds 5 and 6 on the transcriptional reporter suggest that the investigated compounds can only have an indirect p53-dependent mechanism of action. For the compounds 5b, 6b, and 6l, the ROS generation may be one of the significant mechanisms of their cytotoxic action.
Structural Fine-Tuning of Desmuramylpeptide NOD2 Agonists Defines Their in Vivo Adjuvant Activity
Guzelj, Samo,Nabergoj, Sanja,Gobec, Martina,Pajk, Stane,Klan?i?, Veronika,Slütter, Bram,Frkanec, Ru?a,?timac, Adela,?ket, Primo?,Plavec, Janez,Mlinari?-Ra??an, Irena,Jakopin, ?iga
supporting information, p. 7809 - 7838 (2021/06/28)
We report on the design, synthesis, and biological evaluation of a series of nucleotide-binding oligomerization-domain-containing protein 2 (NOD2) desmuramylpeptide agonists with improved in vitro and in vivo adjuvant properties. We identified two promising compounds: 68, a potent nanomolar in vitro NOD2 agonist, and the more lipophilic 75, which shows superior adjuvant activity in vivo. Both compounds had immunostimulatory effects on peripheral blood mononuclear cells at the protein and transcriptional levels, and augmented dendritic-cell-mediated activation of T cells, while 75 additionally enhanced the cytotoxic activity of peripheral blood mononuclear cells against malignant cells. The C18 lipophilic tail of 75 is identified as a pivotal structural element that confers in vivo adjuvant activity in conjunction with a liposomal delivery system. Accordingly, liposome-encapsulated 75 showed promising adjuvant activity in mice, surpassing that of muramyl dipeptide, while achieving a more balanced Th1/Th2 immune response, thus highlighting its potential as a vaccine adjuvant.
Serendipitous base catalysed condensation-heteroannulation of iminoesters: a regioselective route to the synthesis of 4,6-disubstituted 5-azaindoles
Chelvam, Venkatesh,Dudhe, Premansh,Pathak, Biswarup,Venkatasubbaiah, Krishnan
, p. 1582 - 1587 (2020/03/06)
A serendipitous discovery of a novel one-pot synthesis of 4,6-disubstituted 5-azaindoles is reported herein. In the presence of Hunig's base, various N-substituted pyrrole-2-carboxaldehydes have been efficiently transformed into their corresponding 4,6-disubstituted 5-azaindoles through an imine mediated cascade condensation-heteroannulation. The synthetic value of the methodology is established by preparing a novel chemical analogue of a cannabinoid receptor type 2 (CB2) agonist.
