Synthesis, structure prediction, pharmacokinetic properties, molecular docking and antitumor activities of some novel thiazinone derivatives

2015 ◽  
Vol 39 (9) ◽  
pp. 7120-7129 ◽  
Author(s):  
Selvam Athavan Alias Anand ◽  
Chandrasekaran Loganathan ◽  
Nisha Susan Thomas ◽  
Kuppusamy Saravanan ◽  
Antony Therasa Alphonsa ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Structure Prediction ◽  
Antitumor Activities ◽  
Convenient Synthesis ◽  
Pharmacokinetic Properties ◽  
Antitumor Evaluation

Convenient synthesis of [1,3]thiazin-4-ones by the unprecedented cyclization of acetylene diesters with 3-alkyl-2,6-diarylpiperidin-4-one thiosemicarbazone derivatives and their antitumor evaluation.

scholarly journals Synthesis, Antitumor Evaluation and Molecular Docking of New Morpholine Based Heterocycles

Molecules ◽  
2017 ◽  
Vol 22 (7) ◽  
pp. 1211 ◽  
Author(s):  
Zeinab Muhammad ◽  
Mastoura Edrees ◽  
Rasha Faty ◽  
Sobhi Gomha ◽  
Seham Alterary ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Antitumor Evaluation

scholarly journals Design of more potent quinazoline derivatives as EGFRWT inhibitors for the treatment of NSCLC: a computational approach

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Muhammad Tukur Ibrahim ◽  
Adamu Uzairu ◽  
Sani Uba ◽  
Gideon Adamu Shallangwa
Keyword(s):  
Lung Cancer ◽  
Molecular Docking ◽  
Binding Affinity ◽  
Positive Control ◽  
Computational Approach ◽  
Tyrosine Kinase Receptor ◽  
Binding Affinities ◽  
Binding Interaction ◽  
Pharmacokinetic Properties ◽  
Inhibitory Activities

Abstract Background Lung cancer remains the leading and deadly type of cancer worldwide. It was estimated to account for about 25% of the 7 million people that died as a result of cancer-related issues/mortality every year in the world. Non-small cell lung cancer (NSCLC) is the lethal/deadly class of lung cancer with nearly 1.5 million reported cases and less than 20% survival rate. Therefore, it becomes necessary to explore more effective NSCLC drugs. Result A computational approach was employed here to design ten new EGFRWT inhibitors using compound 18 as a template for the design identified with the best binding affinity and good pharmacokinetic properties previously reported in our work. The modeled inhibitory activities of these newly designed EGFRWT inhibitors (range from 7.746966 to 11.09261) were better than that of the hit compound with pIC50 of 7.5639 and gefitinib the positive control with pIC50 of 5.879426. The ligand-binding interaction between these newly designed EGFRWT inhibitors and the EGFR tyrosine kinase receptor as shown in Table 3 was investigated and elucidated using molecular docking protocol. Based on the molecular docking results, the binding affinities of these newly designed EGFRWT inhibitors were found to be between − 8.8 and − 9.5 kcal/mol. The designed compound SFD10 has the highest binding affinity of − 9.5 kcal/mol followed by compound SFD8 (with a binding affinity of − 9.3 kcal/mol), then by compound SFD9 and 4 (each with a binding affinity of − 9.3 kcal/mol). None of them was found to have more than one violation of the filtering criterion used in this study thereby showing good ADMET properties. Conclusion The modeled inhibitory activities and binding affinities of these newly designed EGFRWT inhibitors were found to be higher than that of the template compound and the control (gefitinib) used in this research. They were also seen to be non-toxic with good pharmacokinetic properties.

scholarly journals PREDICTION OF ANTI-ALZHEIMER’S ACTIVITY OF FLAVONOIDS TARGETING CD33 THROUGH IN-SILICO APPROACH

2021 ◽  
pp. 64-66
Author(s):  
AKILA S. ◽  
MALAR VIZHI S. ◽  
VIJAYALAKSHMI P. ◽  
CLARA MARY A. ◽  
RAJALAKSHMI M.
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Molecular Docking ◽  
Social Care ◽  
Docking Studies ◽  
Brain Disorder ◽  
Drug Candidates ◽  
Health And Social Care ◽  
Pharmacokinetic Properties ◽  
Care Systems

Objective: Alzheimer's disease (AD) is a progressive, fatal brain disorder that would be putting a growing strain on health and social care systems. Present anti-AD agents are limited in their application due to their adverse effects, toxicity, and limited targets in AD pathology. As a result, it is important to develop an AD-fighting compound. Some flavonoids (such as kaempferol, myricetin, quercetin, and syringetin) have been shown to be effective in the treatment of Alzheimer's disease. Methods: We chose 284 flavonoids from the NPACT database for molecular docking studies in order to examine their binding interactions with the Alzheimer target protein CD33. Results: These compounds exhibited significant docking interactions with a variety of targets implicated in the pathogenesis of AD. We chose the top three compounds (Rutin, Morin, and,4,4'-Trihydroxydihydrochalcone) based on the scoring parameter. Conclusion: These compounds exhibited favorable pharmacokinetic properties, indicating that they could be attractive drug candidates for the treatment of Alzheimer's disease.

scholarly journals Molecular Docking, Pharmacokinetic Properties and  Toxicity  Studies of  Novel Folate Conjugated To α-Tocopherol via Peptide Bond

2021 ◽  
Author(s):  
Shams H. Abdel-Hafez ◽  
Adil A. Gobouri ◽  
Anber. F. Mohammed ◽  
Mostafa A. Hussein
Keyword(s):  
Molecular Docking ◽  
Folic Acid ◽  
Anticancer Agents ◽  
Folate Receptor ◽  
Peptide Bond ◽  
Docking Study ◽  
Proton Nuclear Magnetic Resonance ◽  
Molecular Docking Study ◽  
Pharmacokinetic Properties ◽  
Human Folate Receptor

Abstract A novel folate conjugated to α-tocopherol (VAF) via peptide bond was Successfully synthesized by using three components vitamin e (α-tocopherol), chloro acetamide and folic acid under mild and simple conditions. The new synthesized compound was characterized by proton nuclear magnetic resonance 1H NMR, 13H NMR and Fourier transform infrared (FT-IR) analysis. A molecular docking study for targeted compound (VAF ) was performed and showed growth-inhibitory activity towards the human folate receptor alpha (FRα) that may affectively the folate uptake by cancer cells. Further, The predicted pharmacokinetic properties and toxicity of the compound (VAF) and folic acid (F) were determined using a statistical analysis (ADMET). It was suggested that pharmacokinetic properties of compound (VAF) represents a promising drug and used as anticancer agents.

scholarly journals Screening for a Potential Therapeutic Agent from the Herbal Formula in the 4th Edition of the Chinese National Guidelines for the Initial-Stage Management of COVID-19 via Molecular Docking

2020 ◽  
Vol 2020 ◽  
pp. 1-17
Author(s):  
Yue Sun ◽  
Angela Wei Hong Yang ◽  
Andrew Hung ◽  
George Binh Lenon
Keyword(s):  
Molecular Docking ◽  
Therapeutic Agent ◽  
Chemical Compounds ◽  
Pharmacokinetic Property ◽  
Herbal Formula ◽  
Stage Management ◽  
National Guidelines ◽  
Initial Stage ◽  
Pharmacokinetic Properties ◽  
Atractylenolide Iii

Background. COVID-19 caused by SARS-CoV-2 infection has been spreading through many countries since the end of 2019. The 4th edition of the national guidelines for the management of COVID-19 provides an herbal formula with 9 herbs for its management. Aim of Study. We aimed to predict the mechanism of binding of SARS-CoV-2 and SARS-CoV spike glycoproteins with angiotensin-converting enzyme 2 (ACE2) to provide a molecular-level explanation of the higher pathogenicity of SARS-CoV-2 and to identify protein sites which may be targeted by therapeutic agents to disrupt virus-host interactions. Subsequently, we aimed to investigate the formula for the initial-stage management to identify a therapeutic agent with the most likely potential to become pharmaceutical candidate for the management of this disease. Materials and Methods. GenBank and SWISS-MODEL were applied for model creation. ClusPro was used for protein-protein docking. PDBePISA was applied for identification of possible binding sites. TCMSP was employed for identification of the chemical compounds. AutoDock Vina together with PyRx was used for the prediction and evaluation of binding pose and affinity to ACE2. SwissADME and PreADME were applied to screening and prediction of the pharmacokinetic properties of the identified chemical compounds. PyMOL was used to visualise the structural models of SARS-CoV-2 and SARS-CoV spike glycoproteins complexed to ACE2 and to examine their interactions. Results. SARS-CoV-2 had two chains (labelled chains B and C) which were predicted to bind with ACE2. In comparison, the SARS-CoV had only one chain (labelled chain C) predicted to bind with ACE2. The spike glycoproteins of both viruses were predicted to bind with ACE2 via position 487. Molecular docking screening and pharmacokinetic property prediction of the herbal compounds indicated that atractylenolide III (−9.1 kcal/mol) from Atractylodes lancea (Thunb.) Dc. (Cangzhu) may be a candidate therapeutic agent for initial-stage management. Conclusions. Atractylenolide III is predicted to have a strong binding affinity with ACE2 and eligible pharmacokinetic properties, anti-inflammatory effects and antiviral effects in in vitro study, and high distribution on the lungs in in vivo study.

Pyridine and Benzoisothiazole Decorated Vanillin Chalcones: Synthesis, Antimicrobial, Antioxidant, Molecular Docking Study and ADMET Properties

2020 ◽  
Vol 17 (5) ◽  
pp. 367-381
Author(s):  
Pintu Pathare ◽  
Sunil Tekale ◽  
Rafique Shaikh ◽  
Manoj Damale ◽  
Jaiprakash Sangshetti ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Antioxidant Activities ◽  
Radical Scavenging ◽  
Docking Study ◽  
Docking Studies ◽  
Pharmacokinetic Parameters ◽  
Molecular Docking Study ◽  
Antimicrobial Drugs ◽  
Discovery Studio ◽  
Pharmacokinetic Properties

Background: The search for new antimicrobial drugs is a never ending task due to microbial resistance to the existing drugs. Antioxidants are essential to prevent free radical reactions which lead to chronic diseases to human kind. Objective: The present studies were aimed to synthesis, characterization, antimicrobial and antioxidant activities of pyridine and benzoisothiazole decorated chalcones. Materials and Methods: FTIR spectra were recorded using KBr pellets on Shimadzu FT-IR spectrophotometer. 1H and 13C NMR spectra were recorded on Bruker 400 MHz spectrometer. Antimicrobial activity of the synthesized chalcones was found to be good against diffenet bacterial and fungal strains. Antioxidant activity was studied in terms of 2,2-diphenyl-1-picrylhydrazyl, hydroxyI and superoxide radical scavenging activities. Molecular docking was studied using Discovery Studio Visualizer Software, version 16 whereas Autodock Vina program was used to predict toxicity profile of the compounds using FAFDrugs2 predictor. Results: The compounds 5c, 5d & 6c showed good antioxidant activities. The insilico molecular docking study supports the experimental results and demonstrated that the chalcones 5d, 6a and 7a are the most active among the synthesized derivatives. Conclusion: Prediction of pharmacokinetic parameters and molecular docking studies suggest that the synthesized chalcones have good pharmacokinetic properties to act as lead molecules in the drug discovery process.

In Vitro Antioxidant, Antimicrobial and Molecular Docking Studies of Fosphenytoin and Regadenoson Impurities

2020 ◽  
Vol 8 (1) ◽  
pp. 63-69
Author(s):  
S. Sathiyanarayanan ◽  
◽  
C.S. Venkatesan ◽  
S. Kabilan ◽  
◽  
...  
Keyword(s):  
Molecular Docking ◽  
Drug Product ◽  
Active Pharmaceutical Ingredient ◽  
Docking Study ◽  
Docking Studies ◽  
Molecular Docking Study ◽  
Gaba A ◽  
Pharmacokinetic Properties ◽  
Approved Drugs

Regadenoson and Fosphenytoin are USFDA approved drugs which is used for coronary vasodilator and convulsive status epileptics respectively. It is quite natural that low levels of reagents or side products are present in the final active pharmaceutical ingredient (API) or drug product as impurities. Such impurities may have unwanted toxicities, including genotoxicity and carcinogenicity. Hence, it is important to study on impurities present in both the drugs. There are 9 impurities were identified from both drugs and studied pharmacokinetic properties using Qikprop module from Schrödinger software. From the 9 compounds of both the drug’s impurities, 5 compounds obey the Lipinski rule of five and the remaining compounds are having 1 to 3 penalties. All the compounds were subjected to molecular docking study with thermo stabilised HUMAN A2A Receptor with adenosine bound protein (PDB ID: 2YDO) for regadenoson impurities and fosphenytoin impurities were docked with Human GABA-A receptor alpha1-beta2-gamma2 subtype in complex with GABA and flumazenil, conformation A protein (PDB id: 6D6U). All the compounds are showed very good interaction with docked proteins. Further selected compound subjected to in vitro Antibacterial (Gram positive, Gram negative), Antifungal and Antioxidant (DPPH and FRAP) studies.

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