scholarly journals Synthesis of Isatin Derivatives Using Silver Nanoparticles as Green Catalyst: Study of Molecular Docking Interactions in SARS-CoV-2 3c-Like Protease and Determination of Cytotoxic Activities of the Compounds

2021 ◽  
Vol 2021 ◽  
pp. 1-17
Author(s):  
Ponnusamy Packialakshmi ◽  
Perumal Gobinath ◽  
Kaliappillai Vijayakumar ◽  
Daoud Ali ◽  
Saud Alarifi ◽  
...  
Keyword(s):  
Silver Nanoparticles ◽  
Molecular Docking ◽  
Nmr Spectroscopy ◽  
Cancer Cell ◽  
In Silico ◽  
Cytotoxic Activities ◽  
In Silico Molecular Docking ◽  
Isatin Derivatives ◽  
Inhibition Ability ◽  
Mcf 7

The coronavirus disease (COVID-19) is caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). As isatin-containing compounds exhibit several remarkable biological activities, isatin derivatives were prepared to combat the global pandemic caused by SARS-CoV-2 that is gripping the world. Herein, the synthesis of novel isatin derivatives has been reported. The cytotoxic activities of the compounds were determined using cancer cell (MCF-7) and normal cell (MCF-10A and MRC-5) lines. In silico molecular docking experiments were conducted using AutoDock Vina. We have successfully predicted the binding energies and the number of hydrogen bonds present. We have also identified the residues involved in hydrogen bond formation. The target compounds were synthesized using Schiff base following cyclization and Knoevenagel condensation reactions. We have focused on the recyclable synthesis of silver nanoparticles (AgNPs) using the extracts obtained from Dipteryx odorata. The extracts were used to reduce silver ions for the production of AgNPs. The synthesized nanoparticles exhibited excellent catalytic activities during the synthesis of isatin derivatives in ethanol. The formation of the target isatin derivatives has been confirmed using the Fourier transform-infrared (FT-IR), proton nuclear magnetic resonance (1H NMR) spectroscopy, 13C NMR spectroscopy, mass spectrometry, and elemental analysis techniques. Compound 3e was found to be the most active compound when tested against the MCF-7 cancer cell line ( I C 50 = 20.5   μ M ). The activity was comparable to the activities of standard doxorubicin and other compounds. In silico molecular docking experiments were conducted to study the spike protein in SARS-CoV-2 (PDB ID: 6LU7). Compound 3c exhibited high binding ability (−9.4 kcal/mol). The inhibition ability was studied using hydroxychloroquine as a standard. Results from docking studies revealed that the inhibition ability of compound 3c was higher than the inhibition abilities exhibited by other compounds. The synthesized compound 3e is a potential antiviral drug that can be used for treating the COVID-19 disease.

Cytotoxic activity and anti-cancer potential of Ontario grown onion extracts against breast cancer cell lines

2018 ◽  
Vol 8 (3) ◽  
pp. 159 ◽  
Author(s):  
Meghan Fragis ◽  
Abdulmonem I. Murayyan ◽  
Suresh Neethirajan
Keyword(s):  
Breast Cancer ◽  
Cytotoxic Activity ◽  
Cell Lines ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Cancer Cell Lines ◽  
Breast Cancer Cell Lines ◽  
Cytotoxic Activities ◽  
Cancer Line ◽  
Mcf 7

Background: Breast cancer is the most commonly diagnosed cancer and the second leading cause of cancer deaths among Canadian women. Cancer management through changes in lifestyle, such as increased intake of foods rich in dietary flavonoids, have been shown to decrease the risk associated with breast, liver, colorectal, and upper-digestive cancers in epidemiologic studies. Onions are high in flavonoid content and one of the most common vegetables. Additionally, onions are used in most Canadian cuisines.Methods: We investigated the effect of five prominent Ontario grown onion (Stanley, Ruby Ring, LaSalle, Fortress, and Safrane) extracts on two subtypes of breast cancer cell lines: a triple negative breast cancer line MDA-MB-231 and an ER+ breast cancer line MCF-7.Results: These onion extracts elicited strong anti-proliferative, anti-migratory, and cytotoxic activities on both the cancer cell lines. Flavonoids present in these onion extracts induced apoptosis, cell cycle arrest in the G2/M phase, and a reduction in mitochondrial membrane potential at dose-dependent concentrations. Onion extracts were more effective against MDA-MB-231 compared to the MCF-7 cell line. Conclusion: In this study, we investigated the extracts synthesized from Ontario-grown onion varieties in inducing anti-migratory, cytostatic, and cytotoxic activities in two sub-types of human breast cancer cell lines. Anti-tumor activity of these extracts depends upon the varietal and can be formulated into nutraceuticals and functional foods for the wellbeing of cancer patients. Overall, the results suggest that onion extracts are a good source of flavonoids with anti-cancerous properties.Keywords: onion extracts; flavonoids; anti-proliferative; breast cancer; cytotoxic activity

The Antiviral and Antimalarial Drug Repurposing in Quest of Chemotherapeutics to Combat COVID-19 Utilizing Structure-Based Molecular Docking

2020 ◽  
Vol 23 ◽  
Author(s):  
Sisir Nandi ◽  
Mohit Kumar ◽  
Mridula Saxena ◽  
Anil Kumar Saxena
Keyword(s):  
Molecular Docking ◽  
In Silico ◽  
Drug Repurposing ◽  
Clinical Settings ◽  
The Novel ◽  
In Silico Docking ◽  
Biochemical Mechanisms ◽  
Novel Coronavirus ◽  
In Silico Molecular Docking

Background: The novel coronavirus disease (COVID-19) is caused by a new strain (SARS-CoV-2) erupted in 2019. Nowadays, it is a great threat that claims uncountable lives worldwide. There is no specific chemotherapeutics developed yet to combat COVID-19. Therefore, scientists have been devoted in the quest of the medicine that can cure COVID- 19. Objective: Existing antivirals such as ASC09/ritonavir, lopinavir/ritonavir with or without umifenovir in combination with antimalarial chloroquine or hydroxychloroquine have been repurposed to fight the current coronavirus epidemic. But exact biochemical mechanisms of these drugs towards COVID-19 have not been discovered to date. Method: In-silico molecular docking can predict the mode of binding to sort out the existing chemotherapeutics having a potential affinity towards inhibition of the COVID-19 target. An attempt has been made in the present work to carry out docking analyses of 34 drugs including antivirals and antimalarials to explain explicitly the mode of interactions of these ligands towards the COVID-19protease target. Results: 13 compounds having good binding affinity have been predicted towards protease binding inhibition of COVID-19. Conclusion: Our in silico docking results have been confirmed by current reports from clinical settings through the citation of suitable experimental in vitro data available in the published literature.

Promising Anti-stroke Signature of Voglibose: Investigation through In- Silico Molecular Docking and Virtual Screening in In-Vivo Animal Studies

2020 ◽  
Vol 20 (3) ◽  
pp. 223-235
Author(s):  
Pooja Shah ◽  
Vishal Chavda ◽  
Snehal Patel ◽  
Shraddha Bhadada ◽  
Ghulam Md. Ashraf
Keyword(s):  
Molecular Docking ◽  
Virtual Screening ◽  
In Silico ◽  
Reductase Activity ◽  
Infarct Volume ◽  
Docking Studies ◽  
Serum Glucose ◽  
In Vivo Studies ◽  
In Silico Molecular Docking

Background: Postprandial hyperglycemia considered to be a major risk factor for cerebrovascular complications. Objective: The current study was designed to elucidate the beneficial role of voglibose via in-silico in vitro to in-vivo studies in improving the postprandial glycaemic state by protection against strokeprone type 2 diabetes. Material and Methods: In-Silico molecular docking and virtual screening were carried out with the help of iGEMDOCK+ Pymol+docking software and Protein Drug Bank database (PDB). Based on the results of docking studies, in-vivo investigation was carried out for possible neuroprotective action. T2DM was induced by a single injection of streptozotocin (90mg/kg, i.v.) to neonates. Six weeks after induction, voglibose was administered at the dose of 10mg/kg p.o. for two weeks. After eight weeks, diabetic rats were subjected to middle cerebral artery occlusion, and after 72 hours of surgery, neurological deficits were determined. The blood was collected for the determination of serum glucose, CK-MB, LDH and lipid levels. Brains were excised for determination of brain infarct volume, brain hemisphere weight difference, Na+-K+ ATPase activity, ROS parameters, NO levels, and aldose reductase activity. Results: In-silico docking studies showed good docking binding score for stroke associated proteins, which possibly hypotheses neuroprotective action of voglibose in stroke. In the present in-vivo study, pre-treatment with voglibose showed a significant decrease (p<0.05) in serum glucose and lipid levels. Voglibose has shown significant (p<0.05) reduction in neurological score, brain infarct volume, the difference in brain hemisphere weight. On biochemical evaluation, treatment with voglibose produced significant (p<0.05) decrease in CK-MB, LDH, and NO levels in blood and reduction in Na+-K+ ATPase, oxidative stress, and aldose reductase activity in brain homogenate. Conclusion: In-silico molecular docking and virtual screening studies and in-vivo studies in MCAo induced stroke, animal model outcomes support the strong anti-stroke signature for possible neuroprotective therapeutics.

Synthesis, In-vitro and Docking Analysis of C-3 substituted Coumarin Analogues as Anticancer Agents C-3 Substituted Coumarins as Anticancer Agents

2020 ◽  
Vol 16 ◽  
Author(s):  
Anuradha Thakur ◽  
Kamalpreet Kaur ◽  
Praveen Sharma ◽  
Ramit Singla ◽  
Sandeep Singh ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Molecular Docking ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Anticancer Agents ◽  
Proliferative Activity ◽  
Binding Interaction ◽  
Diverse Range ◽  
Mcf 7 ◽  
Substituted Coumarins

Background: Breast cancer (BC) is a leading cause of cancer-related deaths in women next to skin cancer. Estrogen receptors (ERs) play an important role in the progression of BC. Current anticancer agents have several drawbacks such as serious side effects and the emergence of resistance to chemotherapeutic drugs. As coumarins possess minimum side effect along with multi-drug reversal activity, it has a tremendous ability to regulate a diverse range of cellular pathways that can be explored for selective anticancer activity. Objectives: Synthesis and evaluation of new coumarin analogues for anti-proliferative activity on human breast cancer cell line MCF-7 along with exploration of binding interaction of the compounds for ER-α target protein by molecular docking. Method: In this study, the anti-proliferative activity of C-3 substituted coumarins analogues (1-17) has been evaluated against estrogen receptor-positive MCF-7 breast cancer cell lines. Molecular interactions and ADME study of the compounds were analyzed by using Schrodinger software. Results: Among the synthesized analogues 12 and 13 show good antiproliferative activity with IC50 values 1and 1.3 µM respectively. Molecular docking suggests a remarkable binding pose of all the seventeen compounds. Compounds 12 and 13 were found to exhibit dock score of -4.10 kcal/mol and -4.38 kcal/mol respectively. Conclusion: Compounds 12 and 13 showed the highest activity followed by 1 and 5. ADME properties of all compounds were in the acceptable range. The active compounds can be taken for lead optimization and mechanistic interventions for their in vivo study in the future.

scholarly journals In Silico Molecular Docking and Interaction Analysis of Traditional Chinese Medicines Against SARS-CoV-2 Receptor

2021 ◽  
Vol 16 (5) ◽  
pp. 1934578X2110150
Author(s):  
Gang Li ◽  
Wei Zhou ◽  
Xiurong Zhao ◽  
Ying Xie
Keyword(s):  
Molecular Docking ◽  
In Silico ◽  
Interaction Analysis ◽  
Herbal Remedies ◽  
Receptor Protein ◽  
Stable Complex ◽  
Traditional Chinese Medicines ◽  
Ligand Interaction ◽  
Chinese Medicines ◽  
In Silico Molecular Docking

The novel coronavirus, 2019-nCoV, has led to a major pandemic in 2020 and is responsible for more than 2.9 million officially recorded deaths worldwide. As well as synthetic anti-viral drugs, there is also a need to explore natural herbal remedies. The Traditional Chinese Medicines (TCMs) system has been used for thousands of years for the prevention, diagnosis, and treatment of several chronic diseases. In this paper, we performed an in silico molecular docking and interaction analysis of TCMs against SARS-CoV-2 receptor RNA-dependent RNA polymerase (RdRp). We obtained the 5 most effective plant compounds which had a better binding affinity towards the target receptor protein. These compounds areforsythoside A, rutin, ginkgolide C, icariside II, and nolinospiroside E. The top-ranked compound, based on docking score, was nolinospiroside, a glycoside found in Ophiopogon japonicas that has antioxidant properties. Protein-ligand interaction analysis discerned that nolinospiroside formed a strong bond between ARG 349 of the protein receptor and the carboxylate group of the ligand, forming a stable complex. Hence, nolinospiroside could be deployed as a lead compound against SARS-CoV-2 infection that can be further investigated for its potential benefits in curbing the viral infection.

scholarly journals In silico molecular docking and in vitro antimicrobial efficacy of phytochemicals against multi-drug-resistant enteroaggregative Escherichia coli and non-typhoidal Salmonella spp.

Gut Pathogens ◽  
2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Padikkamannil Abishad ◽  
Pollumahanti Niveditha ◽  
Varsha Unni ◽  
Jess Vergis ◽  
Nitin Vasantrao Kurkure ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Molecular Docking ◽  
In Silico ◽  
Docking Studies ◽  
Antimicrobial Efficacy ◽  
Drug Resistant ◽  
Protein Motifs ◽  
Phytochemical Compounds ◽  
In Silico Molecular Docking

Abstract Background In the wake of emergence of antimicrobial resistance, bioactive phytochemical compounds are proving to be important therapeutic agents. The present study envisaged in silico molecular docking as well as in vitro antimicrobial efficacy screening of identified phytochemical ligands to the dispersin (aap) and outer membrane osmoporin (OmpC) domains of enteroaggregative Escherichia coli (EAEC) and non-typhoidal Salmonella spp. (NTS), respectively. Materials and methods The evaluation of drug-likeness, molecular properties, and bioactivity of the identified phytocompounds (thymol, carvacrol, and cinnamaldehyde) was carried out using Swiss ADME, while Protox-II and StopTox servers were used to identify its toxicity. The in silico molecular docking of the phytochemical ligands with the protein motifs of dispersin (PDB ID: 2jvu) and outer membrane osmoporin (PDB ID: 3uu2) were carried out using AutoDock v.4.20. Further, the antimicrobial efficacy of these compounds against multi-drug resistant EAEC and NTS strains was determined by estimating the minimum inhibitory concentrations and minimum bactericidal concentrations. Subsequently, these phytochemicals were subjected to their safety (sheep and human erythrocytic haemolysis) as well as stability (cationic salts, and pH) assays. Results All the three identified phytochemicals ligands were found to be zero violators of Lipinski’s rule of five and exhibited drug-likeness. The compounds tested were categorized as toxicity class-4 by Protox-II and were found to be non- cardiotoxic by StopTox. The docking studies employing 3D model of dispersin and ompC motifs with the identified phytochemical ligands exhibited good binding affinity. The identified phytochemical compounds were observed to be comparatively stable at different conditions (cationic salts, and pH); however, a concentration-dependent increase in the haemolytic assay was observed against sheep as well as human erythrocytes. Conclusions In silico molecular docking studies provided useful insights to understand the interaction of phytochemical ligands with protein motifs of pathogen and should be used routinely before the wet screening of any phytochemicals for their antibacterial, stability, and safety aspects.

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