scholarly journals Synthesis and Molecular Docking Studies of New Dispiropyrrolidines on West Nile Virus NS2B-NS3 Protease

2021 ◽  
Vol 21 (6) ◽  
pp. 1431
Author(s):  
Nadia Mohamed Yusoff ◽  
Hasnah Osman ◽  
Mohd. Zaheen Hassan ◽  
Mohamed Ashraf Ali ◽  
Yeong Keng Yoon ◽  
...  
Keyword(s):  
Molecular Docking ◽  
West Nile Virus ◽  
Cycloaddition Reaction ◽  
2D Nmr ◽  
Docking Studies ◽  
West Nile ◽  
Replication Process ◽  
Molecular Docking Studies ◽  
Approved Drugs ◽  
Ns3 Protease

West Nile virus (WNV) is among the other four flavivirus genus, rapidly spreading worldwide. The number of cases increases globally as there are no clinically available approved drugs and vaccines against this disease. Based on our previous finding related to a flavivirus, a series of spiropyrrolidine derivatives were regioselectively synthesized via [3+2]-cycloaddition reaction of three components between isatins, sarcosine, and (E)-3,5-bis (arylidene)-4-piperidones. The yield of synthesized compounds was in a range between 81–95%. The structures of all the synthesized compounds were characterized using FT-IR, 1D- and 2D-NMR, and HRMS. Molecular docking studies of spiropyrrolidines on NS2B-NS3 protease were done to understand and explore the ligand-receptor interactions and hypothesize the drug's refinements. The inhibition of NS2B-NS3 protease has been considered a promising strategy because this enzyme is responsible for the viral replication process. Among them, compound 5c shows an excellent binding affinity with ‒7.71 kcal/mol free binding energy and an inhibition constant of 1.73 μM. It also showed the binding orientation into the active site of WNV NS2B-NS3 protease on Asn84, Tyr1161, Gly1151, and Gly1153.

scholarly journals Potential Inhibitors of SARS-CoV-2 Main Protease (Mpro) Identified from the Library of FDA Approved Drugs Using Molecular Docking Studies

2020 ◽  
Author(s):  
Dipesh Verma ◽  
Srajan Kapoor ◽  
Satyajeet Das ◽  
Krishan Thakur
Keyword(s):  
Molecular Docking ◽  
Therapeutic Potential ◽  
Docking Studies ◽  
Antiviral Compound ◽  
Molecular Docking Studies ◽  
Main Protease ◽  
Approved Drugs ◽  
Fda Approved Drugs

Corona Virus Infectious Disease-2019 (COVID-19) outbreak originated recently at Wuhan, China in December 2019. It has already spread rapidly to more than 200 countries and has been declared a pandemic by WHO. It is caused by a beta-coronavirus named as SARS-CoV-2. There is no definitive cure, either drug or vaccine, to treat or prevent this viral disease. Recently, the crystal structure of the main protease Mpro has been determined. Mpro is responsible for the proteolytic maturation of the polyprotein essential for the viral replication and transcription, which makes it an important drug target. The discovery of new drug molecules may take years before getting to the clinics. So, considering urgency we performed molecular docking studies using FDA approved drugs to identify molecules that could potentially bind to the substrate-binding site and inhibit SARS-CoV-2 main protease (Mpro). We used the Glide module in Schrodinger software suite to perform molecular docking studies followed by MM-GBSA based energy calculations to score the hit molecules. Molecular docking and manual analysis suggest that several drugs may bind and potentially inhibit Mpro. We also performed molecular simulations studies for selected compounds to evaluate protein-drug interactions. Interestingly, we observed only one antiviral compound, Adefovir, in the top50 list of compounds. Considering bioavailability, lesser toxicity, route of administration some of the top-ranked drugs including lumefantrine (antimalarial), dipyridamole (coronary vasodilator), dihydroergotamine (used for treating migraine), hexoprenaline (anti- asthmatic), riboflavin (vitamin B2) and pantethine (vitamin B5) may be taken forward for further in vitro and in vivo experiments to investigate their therapeutic potential.

One-Pot Synthesis of Triazolo-Heterolignans: Biological Evaluation and Molecular Docking Studies as Tubulin Inhibitors

2019 ◽  
Vol 18 (12) ◽  
pp. 1702-1710
Author(s):  
Chada Raji Reddy ◽  
Muppidi Subbarao ◽  
Jonnalagadda Vijaykumar ◽  
Surender Singh Jadav ◽  
Nilesh Sasane ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Molecular Docking ◽  
Binding Site ◽  
Caspase 3 ◽  
Cycloaddition Reaction ◽  
Triazole Ring ◽  
Docking Studies ◽  
Srb Assay ◽  
One Pot ◽  
Molecular Docking Studies

Background: The anti-mitotic activity of podophyllotoxin derivative targeting tubulin enzyme proved them as strong polymerization inhibitors. The introduction of heteroatom along with different heteroaryl systems in naturally obtained lignans created a latitude for design of bioactive components. A novel one-pot sequential propargylation/cycloaddition reaction strategy has been followed to synthesize triazolo-heterolignans. Objective: To screen anti-proliferative activity of novel heterolignans and to determine their mode of action. Method: SRB assay, Cytotoxicity evaluation, PI uptake for analysis of cell cycle, caspase-3 activity, Western blot analysis and Immunofluorescence and molecular docking studies. Results: SRB assay of synthesised compounds were provided compound 3a and 5f to be highly active among the synthesized compounds. The Compound 3a showed cell cycle arrest at G2/M phase and 5f arrest the cells at G1 phase. Compound 5f displayed caspase 3 mediated apoptotic effect at lower levels. Compound 3a and 5f displayed microtubule disassembly inhibition same as paclitaxel and found to be occupying colchicine binding site of tubulin, both ligands were depicted π-cation interaction with Lys352 residue and triazole ring accommodated at the lactone binding site. Conclusion: A novel one-pot sequential propargylation/cycloaddition reaction has been developed for the synthesis of triazolo-heterolignans. Compound 3a and 5f were displayed good cytotoxic activities and found to inhibit microtubule disassembly. The importance of triazole ring of heterolignans has been studied by molecular docking experiments and results were compared.

Homology Modeling of Mus Musculus CDK5 and Molecular Docking Studies with Flavonoids

2017 ◽  
Vol 9 (6) ◽  
Author(s):  
Sowmya Suri ◽  
Rumana Waseem ◽  
Seshagiri Bandi ◽  
Sania Shaik
Keyword(s):  
Molecular Docking ◽  
3D Model ◽  
Structural Features ◽  
Docking Studies ◽  
Amino Acid Residues ◽  
Cyclin Dependent Kinase ◽  
Ligand Complex ◽  
Ligand Interaction ◽  
Molecular Docking Studies ◽  
Cyclin Dependent Kinase 5

A 3D model of Cyclin-dependent kinase 5 (CDK5) (Accession Number: Q543f6) is generated based on crystal structure of P. falciparum PFPK5-indirubin-5-sulphonate ligand complex (PDB ID: 1V0O) at 2.30 Å resolution was used as template. Protein-ligand interaction studies were performed with flavonoids to explore structural features and binding mechanism of flavonoids as CDK5 (Cyclin-dependent kinase 5) inhibitors. The modelled structure was selected on the basis of least modeler objective function. The model was validated by PROCHECK. The predicted 3D model is reliable with 93.0% of amino acid residues in core region of the Ramachandran plot. Molecular docking studies with flavonoids viz., Diosmetin, Eriodictyol, Fortuneletin, Apigenin, Ayanin, Baicalein, Chrysoeriol and Chrysosplenol-D with modelled protein indicate that Diosmetin is the best inhibitor containing docking score of -8.23 kcal/mol. Cys83, Lys89, Asp84. The compound Diosmetin shows interactions with Cys83, Lys89, and Asp84.

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