Discovery, X-ray Crystallography, and Anti-inflammatory Activity of Bromodomain-containing Protein 4 (BRD4) BD1 Inhibitors Targeting a Distinct New Binding Site

Author(s):  
Zhiqing Liu ◽  
Yi Li ◽  
Haiying Chen ◽  
Hsien-Tsung Lai ◽  
Pingyuan Wang ◽  
...  
Marine Drugs ◽  
2021 ◽  
Vol 19 (6) ◽  
pp. 305
Author(s):  
Guangyuan Luo ◽  
Li Zheng ◽  
Qilin Wu ◽  
Senhua Chen ◽  
Jing Li ◽  
...  

Six new fusarin derivatives, fusarins G–L (1–6), together with five known compounds (5–11) were isolated from the marine-derived fungus Fusarium solani 7227. The structures of the new compounds were elucidated by means of comprehensive spectroscopic methods (1D and 2D NMR, HRESIMS, ECD, and ORC) and X-ray crystallography. Compounds 5–11 exhibited potent anti-inflammatory activity by inhibiting the production of NO in RAW264.7 cells activated by lipopolysaccharide, with IC50 values ranging from 3.6 to 32.2 μM. The structure–activity relationships of the fusarins are discussed herein.


Biochemistry ◽  
2002 ◽  
Vol 41 (51) ◽  
pp. 15195-15202 ◽  
Author(s):  
Shin Kawano ◽  
Yoshimitsu Kakuta ◽  
Makoto Kimura

2018 ◽  
Vol 2018 ◽  
pp. 1-11
Author(s):  
Siham Lahsasni ◽  
Dunya A. M. Al-Hemyari ◽  
Hazem A. Ghabbour ◽  
Yahia Nasser Mabkhoot ◽  
Fadilah S. Aleanizy ◽  
...  

Substituted[4,5]thieno[2,3-d]thiazolo[3,2-a]pyrimidin-5-one (3a–b) and pyrimidin-5(6H)-imine (3c–e) were synthesized via reaction of the starting compounds, ethyl 2-amino-substituted[b]thiophene-3-carboxylate (2a–c) and 2-amino-substituted [b]thiophene-3-carbonitrile (2d–f), respectively, with 2-bromothiazole. Synthesis of (bromo-substituted[b]thiophen-2-yl)alkanamide derivatives (4a–e) and thieno[2,3-d][1,3]oxazin-4-imine derivative (5) was accomplished via reaction of the starting compounds with bromoalkyl chloride through nucleophilic substitution; however, for the synthesis of compound 5, nucleophilic substitution was followed by nucleophilic addition to a nitrile group to form the oxazinimine ring. 1-(3-cyano-substituted[b]thiophen-2-yl)-3-(4-(trifluoromethyl)phenyl)thiourea derivatives (6a–c) were obtained via reaction of the starting compounds (2d–f) and 4-(trifluoromethyl phenyl)isothiocyanate. The lead compounds (2d–f) rapidly reacted with 4-(trifluoromethyl)benzaldehyde or 4-(2-pyridyl)benzaldehyde in acidic medium to yield compounds (7a–f) in large quantities. X-ray crystallography of compounds 4c and 7e confirmed their structures. Antimicrobial studies revealed that compound 6a was equally potent to ampicillin against Bacillus strains. Moreover, compounds 3e, 4d, and 6a possessed greater anti-inflammatory potency than that of the standard drug.


1999 ◽  
Vol 274 (8) ◽  
pp. 4917-4923 ◽  
Author(s):  
Brian A. Fox ◽  
Vivien C. Yee ◽  
Lars C. Pedersen ◽  
Isolde Le Trong ◽  
Paul D. Bishop ◽  
...  

2009 ◽  
Vol 5 (4S_Part_14) ◽  
pp. P429-P429
Author(s):  
Warren D. Hirst ◽  
Katie Kubek ◽  
Jonathan Bard ◽  
James Turner ◽  
Kristi Fan ◽  
...  

Author(s):  
Joachim Vogt ◽  
Remo Perozzo ◽  
Alex Pautsch ◽  
Andrea Prota ◽  
Pierre Schelling ◽  
...  

2015 ◽  
Vol 71 (3) ◽  
pp. 541-554 ◽  
Author(s):  
Shigeki Arai ◽  
Yasushi Yonezawa ◽  
Nobuo Okazaki ◽  
Fumiko Matsumoto ◽  
Chie Shibazaki ◽  
...  

Environmentally friendly absorbents are needed for Sr2+and Cs+, as the removal of the radioactive Sr2+and Cs+that has leaked from the Fukushima Nuclear Power Plant is one of the most important problems in Japan. Halophilic proteins are known to have many acidic residues on their surface that can provide specific binding sites for metal ions such as Cs+or Sr2+. The crystal structure of a halophilic β-lactamase fromChromohalobactersp. 560 (HaBLA) was determined to resolutions of between 1.8 and 2.9 Å in space groupP31using X-ray crystallography. Moreover, the locations of bound Sr2+and Cs+ions were identified by anomalous X-ray diffraction. The location of one Cs+-specific binding site was identified in HaBLA even in the presence of a ninefold molar excess of Na+(90 mMNa+/10 mMCs+). From an activity assay using isothermal titration calorimetry, the bound Sr2+and Cs+ions do not significantly affect the enzymatic function of HaBLA. The observation of a selective and high-affinity Cs+-binding site provides important information that is useful for the design of artificial Cs+-binding sites that may be useful in the bioremediation of radioactive isotopes.


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