scholarly journals An in silico approach towards exploration of the oxidative stress resistance of major withanolides of Withania somnifera in relation to COVID-19 management

2021 ◽  
pp. 192-202
Author(s):  
Sangeetha Vinodkumar ◽  
Krishnapriya Santhanu ◽  
Kanimozhi Natarajan ◽  
Kalaiselvi Senthil

Oxidative stress is the state of imbalance between the production of reactive oxygen species (free radicals) in the biological system and the ability of the body to detoxify them resulting in increased accumulation of free radicals in the cells. This stress leads to weakening of the immune system thus leading to higher susceptibility to other infections as well. This also includes the weakening of the respiratory tract leading to increased susceptibility of viral infections as in the case of COVID-19. Treatment for any kind of abnormality requires the identification of the key target proteins and pathways that are being altered. Withania somnifera is being used in the traditional medicinal system to improve health and longevity thus creating a sense of mental as well as physical well being. The present study utilises network pharmacological approach to predict the potential oxidative stress targets of the three major withanolides: withanolide A, withaferin A and withanone. Primarily, the targets of the individual withanolides were obtained from the Swiss target and DIGEP-pred databases and the GO terms and lead hits related to oxidative stress were retrieved from AMIGO2 database. Totally 40 correlative hits were obtained as anti stress targets of the withanolides, which were subjected to functional enrichment and protein–protein interaction analysis to study the enriched pathways underlying oxidative stress response. Further the eleven crucial targets of the four selected pathways were analysed using molecular docking analysis. A total of forty protein hits were obtained as oxidative stress targets of the withanolides. Further, the pathway enrichment of these forty target genes showed the AGE RAGE signalling pathway as highly enriched pathway. Therefore, the AGE RAGE signalling pathway along with its underlying pathways namely MAPK signalling pathway, FOXO pathway and PI3-AKT pathway were chosen among all the other enriched pathways. Further the molecular docking analysis of the eleven target proteins falling under these four pathways showed good docking scores of the withanolides with all the eleven targets with the highest interaction against BCL2.  From the above study, the biological targets and associated pathways of the withanolides have been retrieved.  Thus the in silico approach undertaken in this study explores the role of the key withanolides in the antioxidant potential of the traditional medicinal plant Withania somnifera.

SpringerPlus ◽  
2013 ◽  
Vol 2 (1) ◽  
Author(s):  
Pabba Shiva Krishna ◽  
Kompally Vani ◽  
Metuku Ram Prasad ◽  
Burra Samatha ◽  
Nidadavolu Shesha Venkata Sathya Si Bindu ◽  
...  

BMC Chemistry ◽  
2022 ◽  
Vol 16 (1) ◽  
Author(s):  
Mona Fekadu ◽  
Digafie Zeleke ◽  
Bayan Abdi ◽  
Anuradha Guttula ◽  
Rajalakshmanan Eswaramoorthy ◽  
...  

Abstract Background Quinolines have demonstrated various biological activities such as antimalarial, antibacterial and anticancer. Hence, compounds with such scaffold have been used as lead in drug development. This project is, therefore, aimed to synthesis and evaluates some biological activities of quinoline analogs. Methods 2-Chloro-7-fluoroquinoline-3-carbaldehydes were synthesized by the application of Vilsmeier–Haack reaction. The chlorine in the fluoroquinoline-3-carbaldehyde was replaced with various nucleophiles. The aldehyde functional group was also converted to carboxylic acid and imine groups using oxidizing agent and various amines, respectively. The structures of the compounds synthesized were characterized by spectroscopic methods. Disc diffusion and DPPH assays were used to evaluate the antibacterial and antioxidant activities, respectively. The in silico molecular docking analysis of the synthesized compounds were done using AutoDock Vina against E. coli DNA Gyrase B and human topoisomerase IIα. The drug likeness properties were assessed using SwissADME and PreADMET. Results Nine novel quinoline derivatives were synthesized in good yields. The in vitro antibacterial activity of the synthesized compounds was beyond 9.3 mm inhibition zone (IZ). Compounds 4, 5, 6, 7, 8, 10, 15, and 16 exhibited activity against E. coli, P. aeruginosa, S. aureus and S. pyogenes with IZ ranging from 7.3 ± 0.67 to 15.3 ± 0.33 mm at 200 μg/mL. Compound 9 displayed IZ against three of the bacterial strains except S. aureus. The IC50 for the radical scavenging activity of the synthesized compounds were from 5.31 to 16.71 μg/mL. The binding affinities of the synthesized compounds were from − 6.1 to − 7.2 kcal/mol against E. coli DNA gyrase B and − 6.8 to − 7.4 kcal/mol against human topoisomerase IIα. All of the synthesized compounds obeyed Lipinski’s rule of five without violation. Conclusion Compounds 4, 5, 6, 7, 8, 10, 15, and 16 displayed activity against Gram positive and Gram negative bacterial strains indicating that these compounds might be used as broad spectrum bactericidal activity. Compound 8 (13.6 ± 0.22 mm) showed better IZ against P. aeruginosa compared with ciprofloxacin (10.0 ± 0.45 mm) demonstrating the potential of this compound as antibacterial agent against this strain. Compounds 5, 6, 7, 8, 9 and 10 showed comparable binding affinities in their in silico molecular docking analysis against E. coli DNA gyrase B. All of the synthesized compounds also obeyed Lipinski’s rule of five without violation which suggests these compounds as antibacterial agents for further study. Compounds 7 and 8 were proved to be a very potent radical scavenger with IC50 values of 5.31 and 5.41 μg/mL, respectively. Compound 5, 6, 8, 10 and 16 had comparable binding affinity against human topoisomerase IIα suggesting these compounds as a possible candidate for anticancer drugs.


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