scholarly journals Potential of Withaferin-A, Withanone and Caffeic Acid Phenethyl ester as ATP-competitive inhibitors of BRAF: A bioinformatics study

Author(s):  
Vidhi Malik ◽  
Vipul Kumar ◽  
Sunil C. Kaul ◽  
Renu Wadhwa ◽  
Durai Sundar
Biomolecules ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 160
Author(s):  
Vidhi Malik ◽  
Vipul Kumar ◽  
Sunil C. Kaul ◽  
Renu Wadhwa ◽  
Durai Sundar

The anticancer activities of Withaferin-A (Wi-A) and Withanone (Wi-N) from Ashwagandha and Caffeic Acid Phenethyl Ester (CAPE) from honeybee propolis have been well documented. Here, we examined the binding potential of these natural compounds to inhibit the constitutive phosphorylation of epidermal growth factor receptors (EGFRs). Exon 20 insertion mutants of EGFR, which show resistance to various FDA approved drugs and are linked to poor prognosis of lung cancer patients, were the primary focus of this study. Apart from exon 20 insertion mutants, the potential of natural compounds to serve as ATP competitive inhibitors of wildtype protein and other common mutants of EGFR, namely L858R and exon19del, were also examined. The potential of natural compounds was compared to the positive controls such as erlotinib, TAS6417 and poziotinib. Similar to known inhibitors, Wi-A and Wi-N could displace and binds at the ATP orthosteric site of exon19del, L858R and exon20, while CAPE was limited to wildtype EGFR and exon 20 insertion mutants only. Moreover, the binding free energy of the natural drugs against EGFRs was also comparable to the positive controls. This computational study suggests that Wi-A and Wi-N have potential against multiple mutated EGFRs, warranting further in vitro and in vivo experiments.


Author(s):  
Valeria Pittala ◽  
Luca Vanella ◽  
Loredana Salerno ◽  
Claudia Di Giacomo ◽  
Rosaria Acquaviva ◽  
...  

2021 ◽  
Vol 64 (1) ◽  
Author(s):  
Aslı Özkök ◽  
Merve Keskin ◽  
Aslı Elif Tanuğur Samancı ◽  
Elif Yorulmaz Önder ◽  
Çiğdem Takma

AbstractThis study aimed to determine the standard amount of antioxidant content and compounds of the propolis for the standardization of propolis. For this purpose, the total flavonoids, total phenolic, CUPRAC antioxidant capacity content and the diversity of phenolic and flavonoid components of these propolis samples were found by HPLC determined at the 23 propolis samples which were collected different regions of Turkey. Beside that, the similarities and differences of these 23 provinces to each other according to their antioxidant capacities were investigated by multidimensional scaling analysis. The total flavonoid content in the propolis samples were determined between 21.28 and 152.56 mg CE/g. The total phenolic content in the propolis samples was found between 34.53 mg and 259.4 mg GAE/g. CUPRAC antioxidant capacity of the propolis samples and antioxidant range was found from 95.35 to 710.43 mg TE/g. Also, 4 flavonoid [Quercetin (min.1.12–max.4.14 mg/g), Galangin (min.0.72–max.40.79 mg/g), Apigenin (min.1.07–max.17.35 mg/g), Pinocembrin (min.1.32–max.39.92 mg/g] and 6 phenolic acid [Caffeic acid (min.1.20–max.7.6 mg/g), p-Coumaric acid (min.1.26–max.4.47 mg/g), trans-Ferulic acid (min.1.28–max.4.92 mg/g), Protocatechuic acid (1.78 mg/g), trans-Cinnamic acid (min.1.05–max.3.83 mg/g), Caffeic Acid Phenethyl Ester (CAPE) (min.1.41–max.30.15 mg/g)] components were detected as mg/g, in different ratios in propolis samples collected from different regions. The feature of this study, so far, is to have the maximum number of samples representing the Turkish propolis, and so is thought to help to national and international propolis standard workings.


Life Sciences ◽  
2008 ◽  
Vol 82 (13-14) ◽  
pp. 797-805 ◽  
Author(s):  
Won-Kyo Jung ◽  
Da-Young Lee ◽  
Yung Hyun Choi ◽  
Sung Su Yea ◽  
Inhak Choi ◽  
...  

2017 ◽  
Vol 95 ◽  
pp. 127-132 ◽  
Author(s):  
İbrahim Ağrı ◽  
Arzu Erdal Ağrı ◽  
Mehmet Eser Sancaktar ◽  
Asude Ünal ◽  
Erkan Can ◽  
...  

1988 ◽  
Vol 44 (3) ◽  
pp. 230-232 ◽  
Author(s):  
D. Grunberger ◽  
R. Banerjee ◽  
K. Eisinger ◽  
E. M. Oltz ◽  
L. Efros ◽  
...  

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