6662-53-9Relevant academic research and scientific papers
Synthesis of substituted tryptanthrin via aryl halides and amines as antitumor and anti-MRSA agents
Chen, Huan,Hou, Baolong,Liu, Jianli,Liu, Li,Ma, Xiumei,Wang, Cuiling,Wang, Jilin,Wang, Rui,Wang, Yinyin,Zheng, Xudong
, (2019/11/13)
The natural alkaloid, tryptanthrin (indolo[2,1-b]quinazoline-6,12-dione), and its analogues are found to exhibit potent antitumor and anti-MRSA activities. An efficient and convenient method has been developed for the synthesis of tryptanthrin D-ring derivatives through the reaction of substituted tryptanthrins and secondary amines in moderate to good yields. Some of the new compounds exhibited antitumor activities against the human tumor cell lines A549, HCT116 and MDA-MB-231, with mean IC50 values at low micromolar levels. In addition, some of the compounds showed excellent anti-MRSA activities and were more effective than vancomycin, with MIC values of 0.31–1.25 μg/mL for Mu50,RN4220, and Newman strains.
Synthesis and structure-activity relationship studies of small molecule disruptors of EWS-FLI1 interactions in Ewing's sarcoma
Tosso, Perrer N.,Kong, Yali,Scher, Lauren,Cummins, Ryan,Schneider, Jeffrey,Rahim, Said,Holman, K. Travis,Toretsky, Jeffrey,Wang, Kan,üren, Aykut,Brown, Milton L.
, p. 10290 - 10303 (2015/02/19)
EWS-FLI1 is an oncogenic fusion protein implicated in the development of Ewing's sarcoma family tumors (ESFT). Using our previously reported lead compound 2 (YK-4-279), we designed and synthesized a focused library of analogues. The functional inhibition of the analogues was measured by an EWS-FLI1/NR0B1 reporter luciferase assay and a paired cell screening approach measuring effects on growth inhibition for human cells containing EWS-FLI1 (TC32 and TC71) and control PANC1 cell lines devoid of the oncoprotein. Our data revealed that substitution of electron donating groups at the para-position on the phenyl ring was the most favorable for inhibition of EWS-FLI1 by analogs of 2. Compound 9u (with a dimethylamino substitution) was the most active inhibitor with GI50 = 0.26 ± 0.1 μM. Further, a correlation of growth inhibition (EWS-FLI1 expressing TC32 cells) and the luciferase reporter activity was established (R2 = 0.84). Finally, we designed and synthesized a biotinylated analogue and determined the binding affinity for recombinant EWS-FLI1 (Kd = 4.8 ± 2.6 μM).
Synthesis and antifungal activity of 1-aminomethyl-3-{4- (chlorobenzyloxy) benzoylhydrazono}-4, 5/5, 6-dichloroindolin-2- ones
Harrison, Darwin Anil,Rastogi, Nisheeth,Rahman, Masihur
, p. 411 - 418 (2019/01/21)
3-{4-(Chlorobenzyloxy) benzoylhydrazono}-4,5/5,6-dichloroindolin-2-ones 1a,b-5a,b, were synthesized by the condensation of 4-(chlorobenzyloxy) benzoylhydrazines and 4, 5/5, 6-dichloroindolin-2,3-diones. Compounds 1a,b-5a,b when subjected to Mannich reaction with secondary heterocyclic amines in the presence of formaldehyde, furnished 1-aminomethyl-3-{4-(chlorobenzyloxy) benzoylhydrazono}-4, 5/5, 6-dichloroindolin-2- ones 6a,b-20a,b. The structures of the compounds have been established by means of spectral (IR and 1H NMR) and elemental analysis. The compounds have been screened for their antifungal potential against human pathogenic fungi.
Structural Basis for the Synthesis of Indirubins as Potent and Selective Inhibitors of Glycogen Synthase Kinase-3 and Cyclin-Dependent Kinases
Polychronopoulos, Panagiotis,Magiatis, Prokopios,Skaltsounis, Alexios-Leandros,Myrianthopoulos, Vassilios,Mikros, Emmanuel,Tarricone, Aldo,Musacchio, Andrea,Roe, S. Mark,Pearl, Laurence,Leost, Maryse,Greengard, Paul,Meijer, Laurent
, p. 935 - 946 (2007/10/03)
Pharmacological inhibitors of glycogen synthase kinase-3 (GSK-3) and cyclin-dependent kinases have a promising potential for applications against several neurodegenerative diseases such as Alzheimer's disease. Indirubins, a family of bis-indoles isolated from various natural sources, are potent inhibitors of several kinases, including GSK-3. Using the cocrystal structures of various indirubins with GSK-3β, CDK2 and CDK5/p25, we have modeled the binding of indirubins within the ATP-binding pocket of these kinases. This modeling approach provided some insight into the molecular basis of indirubins' action and selectivity and allowed us to forecast some improvements of this family of bis-indoles as kinase inhibitors. Predicted molecules, including 6-substituted and 5,6-disubstituted indirubins, were synthesized and evaluated as CDK and GSK-3 inhibitors. Control, kinase-inactive indirubins were obtained by introduction of a methyl substitution on N1.
Biological activities and quantitative structure-activity relationships of spiro[imidazolidine-4,4'(1'H)-quinazoline]-2,2',5(3'H)-triones as aldose reductase inhibitors
Yamagishi,Yamada,Ozaki,Asao,Shimizu,Suzuki,Matsumoto,Matsuoka,Matsumoto
, p. 2085 - 2094 (2007/10/02)
A series of spiro[imidazolidine-4,4'(1'H)-quinazoline]-2,2',5(3'H)-triones were prepared and tested for aldose reductase inhibitory activity. The 6'- halogenated derivatives were found to be highly potent in vitro inhibitors of male rabbit lens aldose reductase and in vivo inhibitors of polyol accumulation in the sciatic nerves of galactosemic rats. Of these, (4R)-6'- chloro-3'-methylspiro[imidazolidine-4,4'(1'H)-quinazoline]-2,2',5(3'H)-trione (67) showed the most potent in vitro and in vivo activities. An oral dose of 3 g/kg of compound 67 caused neither death nor behavioral abnormality in the preliminary acute toxicity study using mice and rats. Compound 67 was selected as a candidate for further evaluation. The quantitative structure- activity relationships in this series are also discussed.
