Antioxidant and Antiproliferative Potential of Bioactive Molecules Ursolic Acid and Thujone Isolated from Memecylon edule and Elaeagnus indica and Their Inhibitory Effect on Topoisomerase II by Molecular Docking Approach

The present study aimed to evaluate the antioxidant and antiproliferative potential of ursolic acid and thujone isolated from leaves of Elaeagnus indica and Memecylon edule and their inhibitory effect on topoisomerase II using molecular docking study. The isolated ursolic acid and thujone were examined for different types of free radicals scavenging activity, the antiproliferative potential on U-937 and HT-60 cell lines by adopting standard methods. Further, these compounds were docked with the active site of the ATPase region of topoisomerase II. The findings of the research revealed that ursolic acid harbor strong antioxidant and antiproliferative capacity with low IC50 values than the thujone in all tested methods. Moreover, ursolic acid shows significant inhibition effect on topoisomerase II with a considerable docking score (−8.0312) and GLIDE energy (−51.86 kca/mol). The present outcome concludes that ursolic acid possesses significant antioxidant and antiproliferative potential, which can be used in the development of novel antioxidant and antiproliferative agents in the future.

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Molecular Docking Study for Analyzing the Inhibitory Effect of Anti-inflammatory Plant Compound Against Tumour Necrosis Factor (TNF-α)

Current Drug Therapy ◽

10.2174/1574885513666180503145352 ◽

2019 ◽

Vol 14 (1) ◽

pp. 85-90

Author(s):

Sagarika Biswas

Keyword(s):

Molecular Docking ◽

Tumour Necrosis Factor ◽

Tumour Necrosis ◽

Docking Study ◽

Developed Countries ◽

Inhibitory Effect ◽

Molecular Docking Study ◽

Drug Designing ◽

Anti Inflammatory ◽

Necrosis Factor

Background: Rheumatoid Arthritis (RA) is an autoimmune disorder of symmetric synovial joints which is characterized by the chronic inflammation with 0.5-1% prevalence in developed countries. Presence of persistent inflammation is attributed to the major contribution of key inflammatory cytokine and tumour necrosis factor- alpha (TNF- α). Recent drug designing studies are developing TNF-α blockers to provide relief from the symptoms of the disease such as pain and inflammation. Available blockers are showing certain limitations such as it may enhance the rate of tuberculosis (TB) occurrence, lymphoma risk, cost issues and certain infections are major concern. Discussed limitations implicated a need of development of some alternative drugs which exhibit fewer side effects with low cost. Therefore, we have identified anti-inflammatory compounds in an underutilized fruit of Baccaurea sapida (B.sapida) in our previous studies. Among them quercetin have been identified as the most potent lead compound for drug designing studies of RA. Methods: In the present article, characterization of quercetin has been carried out to check its drug likeliness and molecular docking study has been carried out between TNF- α and quercetin by using AutoDock 4.2.1 software. Further, inhibitory effect of B. sapida fruit extract on RA plasma has been analysed through immunological assay ELISA. Results: Our in-silico analysis indicated that quercetin showed non carcinogenic reaction in animal model and it may also cross the membrane barrier easily. We have studied the ten different binding poses and best binding pose of TNF-α and quercetin showed -6.3 kcal/mol minimum binding energy and 23.94 µM inhibitory constant. In addition to this, ELISA indicated 2.2 down regulated expression of TNF-α in RA compared to control. Conclusion: This study may further be utilized for the drug designing studies to reduce TNF-α mediated inflammation in near future. This attempt may also enhance the utilization of this plant worldwide.

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Investigation of Anti-Coronavirus, Anti-HCV, Nucleotide Inhibitors, and Bioactive Molecules efficacy Against RNA-directed RNA polymerase of Nipah Virus: Molecular Docking Study

Frontiers in Health Informatics ◽

10.30699/fhi.v10i1.288 ◽

2021 ◽

Vol 10 (1) ◽

pp. 78

Author(s):

Peter T. Habib

Keyword(s):

Molecular Docking ◽

Rna Polymerase ◽

Nipah Virus ◽

Docking Study ◽

The Philippines ◽

Bioactive Molecules ◽

World Health ◽

Energy Estimates ◽

Molecular Docking Study ◽

Rna Dependent Rna Polymerase

Introduction: The infections with the Nipah virus (NiV) are highly infectious and may lead to severe febrile encephalitis. High mortality rates in southeastern Asia, including Bengal, Malaysia, Papua New Guinea, Vietnam, Cambodia, Indonesia, Madagascar, the Philippines, Thailand, and India, have been reported in NiV outbreaks. Considering the high risk of an epidemic, NiV was declared a priority pathogen by the World Health Organization. However, for the treatment of this infection, there is no effective therapy or approved FDA medicines. RNA-dependent polymerase RNA (RdRp) plays an important role in viral replication among the nine well-known proteins of NiV.Material and Methods: Fourteen antiviral molecules have been computerized for NiV RNA-dependent RNA polymerase and demonstrated a potential inhibition effect against coronavirus (NiV-RdRp). A multi-step molecular docking process, followed by extensive analyzes of molecular binding interactions, binding energy estimates, synthetic accessibility assessments, and toxicity tests.Results: Molecular docking analysis reveals that Uprifosbuvir is the most suitable inhibitor for RdRp of Nipah Virus regarding the binding affinity and binding in the target cavity. Although, such studies need clinical confirmation.Conclusion: The role of anti-viral molecules as a ligand against RNA-dependent RNA polymerase is critical important in the current era. Computational tools such as molecular docking has proven its power in the analysis of molecules interaction. Our analysis reveals the Uprifosbuvir might be a candidate RdRp inhibitor. This study should further investigate the properties of the already identified anti-viral molecules followed by a pharmacological investigation of these in-silico findings in suitable models.

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MOLECULAR DOCKING STUDY BETWEEN 3 THAI MEDICINAL PLANTS COMPOUNDS AND COVID-19 THERAPEUTIC PROTEIN TARGETS: SARS-COV-2 MAIN PROTEASE, ACE-2, AND PAK-1

International Journal of Applied Pharmaceutics ◽

10.22159/ijap.2021.v13s2.08 ◽

2021 ◽

pp. 41-48

Author(s):

SAFIRA CANDRA ASIH ◽

RAFIDHA IRDIANI ◽

MUHAMAD SAHLAN ◽

MOHAMMAD NASIKIN

Keyword(s):

Molecular Docking ◽

Medicinal Plants ◽

Profile Analysis ◽

Binding Free Energy ◽

Docking Study ◽

Molecular Docking Study ◽

Protein Targets ◽

Main Protease ◽

Docking Approach ◽

Thai Medicinal Plants

Objective: The present study aimed to evaluate those 3 compounds among 122 Thai natural products by using a molecular docking approach to inhibit Main Protease (Mpro) of SARS-CoV-2 (PDB code: 6Y2F), Angiotensin Converting Enzyme (ACE)-2 (PDB code: 1R4L), and PAK-1 kinase (PDB code: 5DEW). Methods: The evaluation was performed on the docking scores calculated using AutoDock Vina as a docking engine and interaction profile analysis through 2-dimensional visualization using LigPlot+. The determination of the docking score was done by selecting the conformation of the ligand that has the lowest binding free energy (best pose). Result: The results of this study indicate that overall, Panduratin A has the best affinity in inhibiting the main protease of SARS-CoV-2, ACE-2, and PAK-1 compared to other compounds. Conclusion: The three thai medicinal plants compound has the potential to be developed as specific therapeutic agents against COVID-19.

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Investigation of Anti-Coronavirus, Anti-HCV, Nucleotide Inhibitors, and Bioactive Molecules efficacy Against RNA-directed RNA polymerase of Nipah Virus: Molecular Docking Study

10.21203/rs.3.rs-294115/v1 ◽

2021 ◽

Author(s):

Peter T. Habib

Keyword(s):

Molecular Docking ◽

Rna Polymerase ◽

Nipah Virus ◽

Docking Study ◽

The Philippines ◽

Bioactive Molecules ◽

World Health ◽

Energy Estimates ◽

Toxicity Tests ◽

Molecular Docking Study

Abstract The infections with the Nipah virus (NiV) are highly infectious and may lead to severe febrile encephalitis. High rates of mortality in southeastern Asia including Bengal, Malaysia, Papua New Guinea, Vietnam, Cambodia, Indonesia, Madagascar, the Philippines, Thailand, and India have been reported in NiV outbreaks. Considering the high risk of an epidemic, NiV was declared a priority pathogen by the World Health Organization (WHO). However, for the treatment of this infection, there is no effective therapy or approved FDA medicines. RNA-dependent polymerase RNA (RdRp) plays an important role in viral replication among the nine well-known proteins of NiV. Therefore, fourteen antiviral molecules have been computerized for NiV RNA-dependent RNA polymerase and demonstrated a potential inhibition effect against coronavirus (NiV-RdRp). A multi-step molecular docking process, followed by extensive analyzes of molecular binding interactions, binding energy estimates, synthetic accessibility assessments, and toxicity tests. Analysis reveals that Uprifosbuvir is the most suitable inhibitor for RdRp of Nipah Virus regarding the binding affinity and binding in the target cavity. Although, such studies need clinical confirmation.

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Thymoquinone: A Review of Pharmacological Importance, Oxidative Stress, COVID-19, and Radiotherapy

Mini-Reviews in Medicinal Chemistry ◽

10.2174/1389557522666220104151225 ◽

2022 ◽

Vol 22 ◽

Author(s):

Seyithan Taysi ◽

Firas Shawqi Algburi ◽

Zaid Mohammed ◽

Omeed Akbar Ali ◽

Muhammed Enes Taysi

Keyword(s):

Molecular Docking ◽

Alternative Medicine ◽

Nigella Sativa ◽

Serine Proteinase ◽

Receptor Site ◽

Docking Study ◽

Inhibitory Effect ◽

Docking Studies ◽

Molecular Docking Study ◽

Main Component

Widely consumed worldwide, Nigella sativa (NS) is a medicinal herb commonly used in various alternative medicine systems such as Unani and Tibb, Ayurveda, and Siddha. Recommended for regular use in Tibb-e-Nabwi (Prophetic Medicine), NS is considered one of the most notable forms of healing medicine in Islamic literature. Thymoquinone (TQ), the main component of the essential oil of NS, has been reported to have many properties such as antioxidant, anti-inflammatory, antiviral, and antineoplastic. Its chemical structure indicates antiviral potential against many viruses, including the hepatitis C virus, human immunodeficiency virus, and other coronavirus diseases. Interestingly, molecular docking studies have demonstrated that TQ can potentially inhibit the development of the coronavirus disease 2019 (COVID-19) by binding to the receptor site on the transmembrane serine proteinase 2 (the activator enzyme that attaches the virus to the cell). In addition, TQ has been shown to be effective against cancer cells due to its inhibitory effect by binding to the different regions of MDM2, according to the proposed molecular docking study. Detailed in this review is the origin of TQ, its significance in alternative medicine, pharmacological value, potential as a cancer anti-proliferative agent, use against the coronavirus disease 2019 (COVID-19), and treatment of other diseases.

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Petra/Osiris/Molinspiration and Molecular Docking Analyses of 3-Hydroxy-Indolin-2-one Derivatives as Potential Antiviral Agents

Current Computer - Aided Drug Design ◽

10.2174/1573409916666191226110029 ◽

2019 ◽

Vol 16 ◽

Author(s):

Taibi Ben Hadda ◽

Vesna Rastija ◽

Faisal AlMalki ◽

Abderrahim Titi ◽

Rachid Touzani ◽

...

Keyword(s):

Molecular Docking ◽

Structural Parameters ◽

Antiviral Agents ◽

Chemical Properties ◽

Docking Study ◽

Bioactive Molecules ◽

Geometrical Parameters ◽

Molecular Docking Study ◽

Catalytic Core ◽

Hiv 1

Background: Studies on the interaction between bioactive molecules and HIV-1 virus has been the focus of recent research in the scope of medicinal chemistry and pharmacology. Objective: Investigating the structural parameters and physic-chemical properties of elucidating and identifying of the antiviral pharmacophore sites. Method: A mixed computational Petra/Osiris/Molinspiration/DFT (POM/DFT) based model has been developed for the identification of physico-chemical parameters governing the bioactivity of 22 3-hydroxy-indolin-2-one derivatives of diacetyl-L-tartaric acid and aromatic amines containing combined antiviral/antitumor/antibacterial pharmacophore sites. Molecular docking study was carried out with HIV-1 integrase (pdb ID: 5KGX) in order to provide information about interactions in the binding site of enzyme. Results: The POM analyses of physic-chemical properties and geometrical parameters of compounds 3a-5j, show that they are bearing a two combined (O,O)-pockets leading to a special platform which able to coordinate two transition metals. The increased activity of series 3a-5j, as compared to standard drugs, contains an (Osp2,O sp3,O sp2)-pharmacophore site. The increase of bioactivity from 4b (R1, R2 = H, H) to 3d (R1, R2 = 4-Br, 2-OCH3) could be attributed to the existence of pi-charge transfer from para-bromo-phenyl to its amid group (COδ---NHδ+). Similar to the indole-based reference ligand (pdb: 7SK), compound 3d forms hydrogen bonding interactions between the residues Glu170, Thr174 and His171 of HIV-1 integrase in catalytic core domain of enzyme. Conclusion: Study confirmed the importance of oxygen atoms, especially from the methoxy group of the phenyl ring, and electrophilic amide nitrogen atom for formation of interactions.

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Divergent de novo synthesis of 2,4,5-trideoxyhexopyranosides derivatives of podophyllotoxin as anticancer agents

Future Medicinal Chemistry ◽

10.4155/fmc-2018-0593 ◽

2019 ◽

Vol 11 (23) ◽

pp. 3015-3027 ◽

Cited By ~ 2

Author(s):

Yapeng Lu ◽

Lu Wang ◽

Xinyang Wang ◽

Haoliang Yuan ◽

Yu Zhao

Keyword(s):

Molecular Docking ◽

Anticancer Agents ◽

De Novo ◽

Docking Study ◽

Inhibitory Effect ◽

De Novo Synthesis ◽

Molecular Docking Study ◽

Cytotoxicity Activity ◽

Derivatives Of ◽

Mcf 7

Aim: Identification of new anticancer glycosidic derivatives of podophyllotoxin. Methods: 14 podophyllotoxin D- and L-monosaccharides have been synthesized in three steps employing de novo glycosylation strategy, and their abilities to inhibit the growth of HeLa, HepG2, MCF-7, A549 and MDA-MB-231 cancer cells were investigated by MTT assay. Molecular docking study of compound 5j with tubulin was performed. Immunofluorescence was applied for detecting the inhibitory effect of 5j on tubulin polymerization. Results & conclusion: Most of synthesized compounds showed strong cytotoxicity activity against five cancer cell lines. Compound 5j possessed the highest cytotoxicity with the IC50 values from 41.6 to 95.2 nM, and could concentration-dependently inhibit polymerization of the microtubule cytoskeleton of MCF-7 cells. Molecular docking disclosed that sugar moiety-dedicated hydrogen bond endowed 5j a higher binding affinity for tubulin.

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Novel Pyrimidine Derivatives as Potential Anticancer Agents: Synthesis, Biological Evaluation and Molecular Docking Study

International Journal of Molecular Sciences ◽

10.3390/ijms22083825 ◽

2021 ◽

Vol 22 (8) ◽

pp. 3825

Author(s):

Beata Tylińska ◽

Benita Wiatrak ◽

Żaneta Czyżnikowska ◽

Aneta Cieśla-Niechwiadowicz ◽

Elżbieta Gębarowska ◽

...

Keyword(s):

Molecular Docking ◽

Anticancer Agents ◽

Topoisomerase Ii ◽

Colon Adenocarcinoma ◽

Docking Study ◽

Biological Evaluation ◽

Dermal Fibroblasts ◽

Pyrimidine Derivatives ◽

Molecular Docking Study

In the present paper, new pyrimidine derivatives were designed, synthesized and analyzed in terms of their anticancer properties. The tested compounds were evaluated in vitro for their antitumor activity. The cytotoxic effect on normal human dermal fibroblasts (NHDF) was also determined. According to the results, all the tested compounds exhibited inhibitory activity on the proliferation of all lines of cancer cells (colon adenocarcinoma (LoVo), resistant colon adenocarcinoma (LoVo/DX), breast cancer (MCF-7), lung cancer (A549), cervical cancer (HeLa), human leukemic lymphoblasts (CCRF-CEM) and human monocytic (THP-1)). In particular, their feature stronger influence on the activity of P-glycoprotein of cell cultures resistant to doxorubicin than doxorubicin. Tested compounds have more lipophilic character than doxorubicin, which determines their affinity for the molecular target and passive transport through biological membranes. Moreover, the inhibitory potential against topoisomerase II and DNA intercalating properties of synthesized compounds were analyzed via molecular docking.

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Solvent-Free Synthesis, DNA-Topoisomerase II Activity and Molecular Docking Study of New Asymmetrically N,N'-Substituted Ureas

Molecules ◽

10.3390/molecules171112882 ◽

2012 ◽

Vol 17 (11) ◽

pp. 12882-12894 ◽

Cited By ~ 5

Author(s):

Andressa Esteves-Souza ◽

Claudio Rodrigues-Santos ◽

Catarina Del Cistia ◽

Daniel Silva ◽

Carlos Sant'Anna ◽

...

Keyword(s):

Molecular Docking ◽

Topoisomerase Ii ◽

Docking Study ◽

Solvent Free ◽

Dna Topoisomerase Ii ◽

Molecular Docking Study ◽

Dna Topoisomerase ◽

Solvent Free Synthesis

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Molecular Docking Study of Several Antiviral Drugs to Defeat Covid-19

Mapana Journal of Sciences ◽

10.12723/mjs.54.4 ◽

2020 ◽

Vol 19 (3) ◽

pp. 37-46

Author(s):

Jasdev S. Tuteja ◽

Priti Patidar ◽

Shilpa E. Mathew ◽

Anil Prajapati

Keyword(s):

Molecular Docking ◽

Severe Acute Respiratory Syndrome ◽

Active Drug ◽

Data Bank ◽

Docking Study ◽

Antiviral Drugs ◽

Binding Affinities ◽

Molecular Docking Study ◽

Molegro Virtual Docker ◽

Docking Approach

Corona virus is one of the significant pathogens that destructs the human respiratory functioning. Deaths and casualties caused by coronaviruses (CoVs) include the severe acute respiratory syndrome (SARS)-CoV and the Middle East respiratory syndrome (MERS)-CoV. The aim of the work was to compare several antiviral drugs and find out which is the most active drug that might be used in treatment for COVID -19. In this study Molecular Docking approach was used to determine the binding affinities of 62 antiviral molecules. The study was carried out using Molegro Virtual Docker 6.0 with PDB 2GTB procured from RCSB Protein Data Bank. Simeprevir and Telaprevir were discovered to be most potent having high MolDock and Rerank scores of -225.158, -78.4383 and -209.467, -136.155 respectively. Further studies may be conducted to design more potent analogue and defeat COVID-19.

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