Synthesis and Biological Screening of Silicon-Containing Ibuprofen Derivatives: A Study of Their NF-κβ Inhibitory Activity, Cytotoxicity, and Their Ability to Bind IKKβ

2016 ◽  
Vol 69 (6) ◽  
pp. 662 ◽  
Author(s):  
David J. Pérez ◽  
Uzma I. Zakai ◽  
Song Guo ◽  
Ilia A. Guzei ◽  
Zeferino Gómez-Sandoval ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Molecular Docking ◽  
Inhibitory Activity ◽  
Biological Screening ◽  
Nuclear Transcription Factor ◽  
Docking Calculation ◽  
Significant Toxicity ◽  
Key Residues ◽  
Better Than

The synthesis and characterisation of new silicon-containing amides and esters derived from ibuprofen is reported. These compounds were tested against nuclear transcription factor κβ (NF-κβ). Higher inhibition values than those of ibuprofen were achieved by the new amides 10a–10d; ester derivatives did not show inhibitory activity. The cytotoxicity of these new derivatives was screened; none of them displayed significant toxicity at the screened doses. A molecular docking calculation on IKKβ (an enzyme related to NF-κβ activation) was carried out and the results showed that the amides interact better than ibuprofen with key residues, which are important to the inhibition of IKKβ.

scholarly journals Discovery of 8-Amino-Substituted 2-Phenyl-2,7-Naphthyridinone Derivatives as New c-Kit/VEGFR-2 Kinase Inhibitors

Molecules ◽  
2019 ◽  
Vol 24 (24) ◽  
pp. 4461 ◽  
Author(s):  
Haiyan Sun ◽  
Linsheng Zhuo ◽  
Huan Dong ◽  
Wei Huang ◽  
Nengfang She
Keyword(s):  
Molecular Docking ◽  
Inhibitory Activity ◽  
Kinase Inhibitors ◽  
Biological Screening ◽  
Binding Interactions ◽  
Lead Structure ◽  
Lead Compounds ◽  
Ic50 Value ◽  
Ic50 Values ◽  
Insight Into

The 2,7-naphthyridone scaffold has been proposed as a novel lead structure of MET inhibitors by our group. To broaden the application of this new scaffold, a series of 8-amino-substituted 2-phenyl-2,7-naphthyridin-1(2H)-one derivatives were designed and synthesized. Preliminary biological screening resulted in the discovery of a new lead of c-Kit and VEGFR-2 kinase inhibitors. Compound 9k exhibited excellent c-Kit inhibitory activity, with an IC50 value of 8.5 nM, i.e., it is 38.8-fold more potent than compound 3 (IC50 of 329.6 nM). Moreover, the compounds 10l and 10r exhibited good VEGFR-2 inhibitory activity, with IC50 values of 56.5 and 31.7 nM, respectively, i.e., they are 5.0–8.8-fold more potent than compound 3 (IC50 of 279.9 nM). Molecular docking experiments provided further insight into the binding interactions of the new lead compounds with c-Kit and VEGFR-2 kinase. In this study, an 8-amino-substituted 2-phenyl-2,7-naphthyridin-1(2H)-one scaffold was identified as the new lead structure of c-Kit and VEGFR-2 kinase inhibitors.

Isolation of tetramer stilbenoids from Shorea leprosula Miq., acetylcholinesterase inhibitory activity and molecular docking study

2019 ◽  
Author(s):  
AS Kamarozaman ◽  
N Ahmat ◽  
MSM Johari ◽  
ZZ Hafiz ◽  
MI Adenan ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Inhibitory Activity ◽  
Docking Study ◽  
Molecular Docking Study ◽  
Acetylcholinesterase Inhibitory Activity ◽  
Shorea Leprosula

Roles of osteopontin and nuclear transcription factor in chronic cyclosporine nephrotoxicity

2014 ◽  
Vol 35 (5) ◽  
pp. 476
Author(s):  
Mei-rong FANG ◽  
Ying-shun JIN ◽  
Ji-zhe JIN ◽  
Zhen-hua CUI ◽  
Hai-feng JIN ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Nuclear Transcription Factor ◽  
Cyclosporine Nephrotoxicity

Design, Synthesis, Molecular Docking and Biological Evaluation of 1-(benzo[d]thiazol-2-ylamino)(phenyl)methyl)naphthalen-2-ol Derivatives as Antiproliferative Agents

2019 ◽  
Vol 16 (10) ◽  
pp. 837-845
Author(s):  
Sandhya Jonnala ◽  
Bhaskar Nameta ◽  
Murthy Chavali ◽  
Rajashaker Bantu ◽  
Pallavi Choudante ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Inhibitory Activity ◽  
Chinese Hamster Ovary Cells ◽  
Chinese Hamster ◽  
Mouse Skin ◽  
Coupling Reaction ◽  
Binding Mode ◽  
Biological Evaluation ◽  
Design Synthesis

A class of 1-((benzo[d]thiazol-2-ylamino)(phenyl)methyl)naphthalen-2-ol derivatives (4a-t) has been synthesized in good yields through a three component coupling reaction. The newly synthesized compounds were evaluated for their in vitro antiproliferative activity against five cell lines such as DU145 (human prostate cancer), MDA-MB-B231 (human breast cancer), SKOV3 (human ovarian cancer), B16-F10 (mouse skin melanoma) and CHO-K1 (Chinese hamster ovary cells), a noncancerous cell line. In vitro inhibitory activity indicates that compounds 4a, 4b, 4c, 4d, 4g, 4j, and 4o exhibited potent anti-proliferative behavior. Among them, compounds 4g, 4j and 4o found to be the most active members exhibiting remarkable growth inhibitory activity. Molecular docking facilitates to investigate the probable binding mode and key active site interactions in tubulins α and β proteins. The docking results are complementary to experimental results.

2,4-Dichloro-5-[(N-aryl/alkyl)sulfamoyl]benzoic Acid Derivatives: In Vitro Antidiabetic Activity, Molecular Modeling and In silico ADMET Screening

2019 ◽  
Vol 15 (2) ◽  
pp. 186-195 ◽  
Author(s):  
Samridhi Thakral ◽  
Vikramjeet Singh
Keyword(s):  
Molecular Docking ◽  
Benzoic Acid ◽  
Inhibitory Activity ◽  
In Silico ◽  
Computational Study ◽  
Antidiabetic Activity ◽  
Standard Drug ◽  
Benzoic Acid Derivatives ◽  
In Silico Admet ◽  
Inhibitory Potential

Background: Postprandial hyperglycemia can be reduced by inhibiting major carbohydrate hydrolyzing enzymes, such as α-glucosidase and α-amylase which is an effective approach in both preventing and treating diabetes. Objective: The aim of this study was to synthesize a series of 2,4-dichloro-5-[(N-aryl/alkyl)sulfamoyl] benzoic acid derivatives and evaluate α-glucosidase and α-amylase inhibitory activity along with molecular docking and in silico ADMET property analysis. Method: Chlorosulfonation of 2,4-dichloro benzoic acid followed by reaction with corresponding anilines/amines yielded 2,4-dichloro-5-[(N-aryl/alkyl)sulfamoyl]benzoic acid derivatives. For evaluating their antidiabetic potential α-glucosidase and α-amylase inhibitory assays were carried out. In silico molecular docking studies of these compounds were performed with respect to these enzymes and a computational study was also carried out to predict the drug-likeness and ADMET properties of the title compounds. Results: Compound 3c (2,4-dichloro-5-[(2-nitrophenyl)sulfamoyl]benzoic acid) was found to be highly active having 3 fold inhibitory potential against α-amylase and 5 times inhibitory activity against α-glucosidase in comparison to standard drug acarbose. Conclusion: Most of the synthesized compounds were highly potent or equipotent to standard drug acarbose for inhibitory potential against α-glucosidase and α-amylase enzyme and hence this may indicate their antidiabetic activity. The docking study revealed that these compounds interact with active site of enzyme through hydrogen bonding and different pi interactions.

scholarly journals Angiotensin II activates nuclear transcription factor-κB through AT1 and AT2 receptors11See Editorial by Luft, p. 2272.

2002 ◽  
Vol 61 (6) ◽  
pp. 1986-1995 ◽  
Author(s):  
Gunter Wolf ◽  
Ulrich Wenzel ◽  
Kevin D. Burns ◽  
Raymond C. Harris ◽  
Rolf A.K. Stahl ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Angiotensin Ii ◽  
Nuclear Transcription Factor

New Diclofenac Derivatives as Anti-Microbial, Anti-Inflammatory Agents: Design, Synthesis, Biological Screening, and Molecular Docking Study

2021 ◽  
Vol 47 (1) ◽  
pp. 208-220
Author(s):  
Mahmoud M. Hamed ◽  
Adel M. Kamal El-Dean ◽  
Shawkat A. Abdel-Mohsen ◽  
Mahmoud S. Tolba
Keyword(s):  
Molecular Docking ◽  
Docking Study ◽  
Molecular Docking Study ◽  
Biological Screening ◽  
Design Synthesis ◽  
Anti Inflammatory
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