64605-37-4Relevant academic research and scientific papers
4-Chloro-l-kynurenine as fluorescent amino acid in natural peptides
Alferova, Vera A.,Shuvalov, Maxim V.,Suchkova, Taisiya A.,Proskurin, Gleb V.,Aparin, Ilya O.,Rogozhin, Eugene A.,Novikov, Roman A.,Solyev, Pavel N.,Chistov, Alexey A.,Ustinov, Alexey V.,Tyurin, Anton P.,Korshun, Vladimir A.
, p. 1697 - 1705 (2018/09/21)
4-Chloro-l-kynurenine (3-(4-chloroanthraniloyl)-l-alanine, l-4-ClKyn), an amino acid known as a prospective antidepressant, was recently for the first time found in nature in the lipopeptide antibiotic taromycin. Here, we report another instance of its identification in a natural product: 4-chloro-l-kynurenine was isolated from acidic hydrolysis of a new complex peptide antibiotic INA-5812. l-4-ClKyn is a fluorescent compound responsible for the fluorescence of the above antibiotic. Whereas fluorescence of 4-chlorokynurenine was not reported before, we synthesized the racemic compound and studied its emission in various solvents. Next, we prepared conjugates of dl-4-ClKyn with two suitable energy acceptors, BODIPY FL and 3-(phenylethynyl)perylene (PEPe), and studied fluorescence of the derivatives. 4-Chloro-dl-kynurenine emission is not detected in both conjugates, thus evidencing effective energy transfer. However, BODIPY FL emission in the conjugate is substantially reduced, probably due to collisional or photoinduced charge-transfer-mediated quenching. The intrinsic fluorescence of l-4-ClKyn amino acid in antibiotics paves the way for spectral studies of their mode of action.
DEUTERATED CHLOROKYNURENINES FOR THE TREATMENT OF NEUROPSYCHIATRIC DISORDERS
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Paragraph 00158-00160, (2017/05/02)
Described are deuterated chlorokynurenines and compositions, and their application as pharmaceuticals for the treatment of disease. Methods of modulating N-methyl-D-aspartate (NMDA) receptor activity, methods of treating disorders, including neuropsychiatric disorders such as depression, epilepsy, schizophrenia, and Huntington's Disease, and use of said deuterated chlorokynurenines are also described.
METHODS FOR THE SYNTHESIS OF CHIRAL KYNURENINE COMPOUNDS
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Paragraph 0036, (2014/10/04)
Provided are methods for synthesizing compounds, including chiral kynurenine compounds. The methods are suitable for large-scale manufacture and produce the chiral kynurenines compounds in high chemical purity and high chiral purity.
The structure-activity relationships of A-ring-substituted aromathecin topoisomerase i inhibitors strongly support a camptothecin-like binding mode
Cinelli, Maris A.,Morrell, Andrew E.,Dexheimer, Thomas S.,Agama, Keli,Agrawal, Surbhi,Pommier, Yves,Cushman, Mark
experimental part, p. 5535 - 5552 (2010/10/01)
Aromathecins are inhibitors of human topoisomerase I (Top1). These compounds are composites of several heteroaromatic systems, namely the camptothecins and indenoisoquinolines, and they possess notable Top1 inhibition and cytotoxicity when substituted at position 14. The SAR of these compounds overlaps with indenoisoquinolines, suggesting that they may intercalate into the Top1-DNA complex similarly. Nonetheless, the proposed binding mode for aromathecins is purely hypothetical, as an X-ray structure is unavailable. In the present communication, we have synthesized eight novel series of A-ring-substituted (positions 1-3) aromathecins, through a simple, modular route, as part of a comprehensive SAR study. Certain groups (such as 2,3-ethylenedioxy) moderately improve Top1 inhibition, and, often, antiproliferative activity, whereas other groups (2,3-dimethoxy and 3-substituents) attenuate bioactivity. Strikingly, these trends are very similar to those previously observed for the A-ring of camptothecins, and this considerable SAR overlap lends further support (in the absence of crystallographic data) to the hypothesis that aromathecins bind in the Top1 cleavage complex as interfacial inhibitors in a 'camptothecin-like' pose.
New homocamptothecins: Synthesis, antitumor activity, and molecular modeling
Miao, Zhenyuan,Sheng, Chunquan,Zhang, Wannian,Ji, Haitao,Zhang, Jing,Shao, Luecheng,You, Liang,Zhang, Min,Yao, Jianzhong,Che, Xiaoyin
, p. 1493 - 1510 (2008/09/17)
Homocamptothecins (hCPTs) represent a class of new emerging antitumor agents, which contains a seven-membered β-hydroxylactone in place of the conventional six-membered α-hydroxylactone ring (E ring) of camptothecins. Some novel 7-substituted hCPTs were designed and synthesized based on a newly developed synthetic route which couples ring A with ring C, E and D. Most of the synthesized compounds exhibit very high cytotoxic activity on tumor cell line A549. Some compounds, such as 9b, 9l, and 9y, show broad in vitro antitumor spectrum and are more potent than topotecan. Three-dimensional quantitative structure-activity relationship (3D-QSAR) methods, CoMFA and CoMSIA, were applied to explain the structure-activity relationship (SAR) of the synthesized compounds. Furthermore, molecular docking was used to clarify the binding mode of the synthesized compounds to human DNA topoisomerase I. The important hydrophobic, base-pair stacking, and hydrogen-bonding interactions were observed between the hCPT derivatives and their receptor. The results from molecular modeling will guide the design of novel hCPTs with higher antitumor activity.
