scholarly journals Computational Insights into the Potential of Withaferin-A, Withanone and Caffeic Acid Phenethyl Ester for Treatment of Aberrant-EGFR Driven Lung Cancers

Biomolecules ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 160
Author(s):  
Vidhi Malik ◽  
Vipul Kumar ◽  
Sunil C. Kaul ◽  
Renu Wadhwa ◽  
Durai Sundar
Keyword(s):  
Caffeic Acid ◽  
Computational Study ◽  
Binding Free Energy ◽  
Natural Compounds ◽  
Caffeic Acid Phenethyl Ester ◽  
Withaferin A ◽  
Binding Potential ◽  
Exon 20 ◽  
Insertion Mutants ◽  
Positive Controls

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.

scholarly journals Natural products may interfere with SARS-CoV-2 attachment to the host cell

2020 ◽  
Author(s):  
Abdo Elfiky
Keyword(s):  
Host Cell ◽  
Caffeic Acid ◽  
Cell Receptor ◽  
Natural Compounds ◽  
Caffeic Acid Phenethyl Ester ◽  
Biochanin A ◽  
Host Cell Receptor ◽  
Stressed Cells ◽  
Dynamics Simulations ◽  
Natural Product Compounds

Abstract Objectives: SARS-CoV-2 has been emerged in December 2019 in China, causing deadly (5% mortality) pandemic pneumonia, termed COVID-19. More than one host-cell receptor is reported to be recognized by the viral spike protein, among them is the cell-surface Heat Shock Protein A5 (HSPA5), also termed GRP78 or BiP. Upon viral infection, HSPA5 is upregulated, then translocating to the cell membrane where it is subjected to be recognized by the SARS-CoV-2 spike. In this study, some natural product compounds are tested against the HSPA5 substrate-binding domain β (SBDβ), which reported to be the recognition site for the SARS-CoV-2 spike. Methods: Molecular docking and molecular dynamics simulations are used to test some natural compounds binding to HSPA5 SBDβ. Results: The results show high to a moderate binding affinity for the phytoestrogens (Diadiazin, Genistein, Formontein, and Biochanin A), chlorogenic acid, linolenic acid, palmitic acid, caffeic acid, caffeic acid phenethyl ester, hydroxytyrosol, cis-p-Coumaric acid, cinnamaldehyde, and thymoquinone to the HSPA5 SBDβ. Based on its binding affinities, the natural compounds, and some hormones, may interfere with SARS-CoV-2 attachment to the stressed cells. Conclusion: These compounds can be successful as anti-COVID-19 agents for people with a high risk of cell stress like elders, cancer patients, and front-line medical staff.

Novel Caffeic Acid Phenethyl Ester (Cape) Analogues as Inducers of Heme Oxygenase-1

2017 ◽  
Vol 23 (18) ◽  
Author(s):  
Valeria Pittala ◽  
Luca Vanella ◽  
Loredana Salerno ◽  
Claudia Di Giacomo ◽  
Rosaria Acquaviva ◽  
...  
Keyword(s):  
Caffeic Acid ◽  
Heme Oxygenase ◽  
Caffeic Acid Phenethyl Ester ◽  
Heme Oxygenase 1

Machine Learning-based Virtual Screening Strategy Reveals Some Natural Compounds As Potential PAK4 Inhibitors In Triple Negative Breast Cancer

2020 ◽  
Vol 18 ◽  
Author(s):  
Opeyemi Iwaloye ◽  
Olusola Olalekan Elekofehinti ◽  
Babatomiwa Kikiowo ◽  
Emmanuel Ayo Oluwarotimi ◽  
Toyin Mary Fadipe
Keyword(s):  
Breast Cancer ◽  
Virtual Screening ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Binding Free Energy ◽  
Natural Compounds ◽  
Energy Calculation ◽  
Reference Drug ◽  
Predictive Quality

Background: P-21 activating kinase 4 (PAK4) is implicated in poor prognosis of many cancers, especially in the progression of Triple Negative Breast Cancer (TNBC). The present study was aimed at designing some potential drug candidates as PAK4 inhibitors for breast cancer therapy. Objective: This study aimed to finding novel inhibitors of PAK4 from natural compounds using computational approach. Methods: An e-pharmacophore model was developed from docked PAK4-coligand complex and used to screen over a thousand natural compounds downloaded from BIOFACQUIM and NPASS databases to match a minimum of 5 sites for selected (ADDDHRR) hypothesis. The robustness of the virtual screening method was accessed by well-established methods including EF, ROC, BEDROC, AUAC, and the RIE. Compounds with fitness score greater than one were filtered by applying molecular docking (HTVS, SP, XP and Induced fit docking) and ADME prediction. Using Machine learningbased approach QSAR model was generated using Automated QSAR. The computed top model kpls_des_17 (R2= 0.8028, RMSE = 0.4884 and Q2 = 0.7661) was used to predict the pIC50 of the lead compounds. Internal and external validations were accessed to determine the predictive quality of the model. Finally the binding free energy calculation was computed. Results: The robustness/predictive quality of the models were affirmed. The hits had better binding affinity than the reference drug and interacted with key amino acids for PAK4 inhibition. Overall, the present analysis yielded three potential inhibitors that are predicted to bind with PAK4 better than reference drug tamoxifen. The three potent novel inhibitors vitexin, emodin and ziganein recorded IFD score of -621.97 kcal/mol, -616.31 kcal/mol and -614.95 kcal/mol, respectively while showing moderation for ADME properties and inhibition constant. Conclusion: It is expected that the findings reported in this study may provide insight for designing effective and less toxic PAK4 inhibitors for triple negative breast cancer.

Screening and Elucidation of Selected Natural Compounds for Anti- Alzheimer's Potential Targeting BACE-1 Enzyme: A Case Computational Study

2017 ◽  
Vol 13 (4) ◽  
Author(s):  
Syed Sayeed Ahmad ◽  
Salman Akhtar ◽  
Syed Mohd. Danish Rizvi ◽  
Mohammad A. Kamal ◽  
Usman Sayeed ◽  
...  
Keyword(s):  
Computational Study ◽  
Natural Compounds ◽  
Bace 1

scholarly journals Determination of antioxidant activity and phenolic compounds for basic standardization of Turkish propolis

2021 ◽  
Vol 64 (1) ◽  
Author(s):  
Aslı Özkök ◽  
Merve Keskin ◽  
Aslı Elif Tanuğur Samancı ◽  
Elif Yorulmaz Önder ◽  
Çiğdem Takma
Keyword(s):  
Antioxidant Capacity ◽  
Caffeic Acid ◽  
Caffeic Acid Phenethyl Ester ◽  
Total Phenolic ◽  
Scaling Analysis ◽  
Flavonoid Content ◽  
Multidimensional Scaling Analysis ◽  
Flavonoid Quercetin ◽  
Phenolic And Flavonoid

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.

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