scholarly journals Synthesis, in vitro and in vivo biological evaluation, COX-1/2 inhibition and molecular docking study of indole-N-acylhydrazone derivatives

2018 ◽  
Vol 26 (20) ◽  
pp. 5388-5396 ◽  
Author(s):  
Ana Daura Travassos de Oliveira Moraes ◽  
Mirelly Dianne Santos de Miranda ◽  
Íris Trindade Tenório Jacob ◽  
Cézar Augusto da Cruz Amorim ◽  
Ricardo Olímpio de Moura ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Docking Study ◽  
Biological Evaluation ◽  
Molecular Docking Study ◽  
Cox 1

Synthesis of new hexahydropyrimido[1,2-a]azepine derivatives bearing functionalized aryl and heterocyclic moieties as anti-inflammatory agents

2021 ◽  
Author(s):  
Hassanein H Hassanein ◽  
Doaa E Abdel Rahman ◽  
Marwa A Fouad ◽  
Rehab F Ahmed
Keyword(s):  
Molecular Docking ◽  
Binding Sites ◽  
Docking Study ◽  
In Vivo Studies ◽  
Molecular Docking Study ◽  
Cox 2 ◽  
Anti Inflammatory ◽  
Cox 1

New hexahydropyrimido[1,2- a]azepine derivatives bearing functionalized aryl and heterocyclic moieties were synthesized as anti-inflammatory agents with better safety profiles. All synthesized compounds were assessed in vitro for their COX-1 and COX-2 inhibition activities. The most selective compounds, 2f, 5 and 6, were further evaluated for their in vivo anti-inflammatory activity and PGE2 inhibitory activity. To rationalize their selectivity, molecular docking within COX-1 and COX-2 binding sites was performed. Their physicochemical properties and drug-like nature profile were also calculated. The good activity and selectivity of compounds 2f, 5 and 6 were rationalized using a molecular docking study and supported by in vivo studies. These promising findings are encouraging for performing future investigations of these derivatives.

Structure-Based Design, Synthesis, Biological Evaluation and Molecular Docking Study of 4-Hydroxy-N'-methylenebenzohydrazide Derivatives Acting as Tyrosinase Inhibitors with Potentiate Anti-Melanogenesis Activities

2020 ◽  
Vol 16 (7) ◽  
pp. 892-902 ◽  
Author(s):  
Aida Iraji ◽  
Mahsima Khoshneviszadeh ◽  
Pegah Bakhshizadeh ◽  
Najmeh Edraki ◽  
Mehdi Khoshneviszadeh
Keyword(s):  
Molecular Docking ◽  
Active Site ◽  
Competitive Inhibition ◽  
Docking Study ◽  
Biological Evaluation ◽  
Primary Response ◽  
Ratio Method ◽  
Molecular Docking Study ◽  
Metal Chelating

Background: Melanogenesis is a process of melanin synthesis, which is a primary response for the pigmentation of human skin. Tyrosinase is a key enzyme, which catalyzes a ratelimiting step of the melanin formation. Natural products have shown potent inhibitors, but some of these possess toxicity. Numerous synthetic inhibitors have been developed in recent years may lead to the potent anti– tyrosinase agents. Objective: A number of 4-hydroxy-N'-methylenebenzohydrazide analogues with related structure to chalcone and tyrosine were constructed with various substituents at the benzyl ring of the molecule and evaluate as a tyrosinase inhibitor. In addition, computational analysis and metal chelating potential have been evaluated. Methods: Design and synthesized compounds were evaluated for activity against mushroom tyrosinase. The metal chelating capacity of the potent compound was examined using the mole ratio method. Molecular docking of the synthesized compounds was carried out into the tyrosine active site. Results: Novel 4-hydroxy-N'-methylenebenzohydrazide derivatives were synthesized. The two compounds 4c and 4g showed an IC50 near the positive control, led to a drastic inhibition of tyrosinase. Confirming in vitro results were performed via the molecular docking analysis demonstrating hydrogen bound interactions of potent compounds with histatidine-Cu+2 residues with in the active site. Kinetic study of compound 4g showed competitive inhibition towards tyrosinase. Metal chelating assay indicates the mole fraction of 1:2 stoichiometry of the 4g-Cu2+ complex. Conclusion: The findings in the present study demonstrate that 4-Hydroxy-N'- methylenebenzohydrazide scaffold could be regarded as a bioactive core inhibitor of tyrosinase and can be used as an inspiration for further studies in this area.

scholarly journals Identification of Potent Inhibitors of COVID-19 Main Protease Enzyme by Molecular Docking Study

2020 ◽  
Author(s):  
pooja singh ◽  
Angkita Sharma ◽  
Shoma Paul Nandi
Keyword(s):  
Molecular Docking ◽  
Antiviral Drug ◽  
Cyclopiazonic Acid ◽  
Docking Study ◽  
Molecular Docking Study ◽  
Docking Score ◽  
Protease Enzyme ◽  
Main Protease

<p>Within the span of a few months, the severe acute respiratory syndrome coronavirus, COVID-19 (SARS-CoV-2), has proven to be a pandemic, affecting the world at an exponential rate. It is extremely pathogenic and causes communicable infection in humans. Viral infection causes difficulties in breathing, sore throat, cough, high fever, muscle pain, diarrhea, dyspnea, and may lead to death. Finding a proper drug and vaccines against this virus is the need of the hour. The RNA genome of COVID19 codes for the main protease M<sup>pro</sup>, which is required for viral multiplication. To identify possible antiviral drug(s), we performed molecular docking studies. Our screen identified ten biomolecules naturally present in <i>Aspergillus flavus</i> and <i>Aspergillus oryzae</i> fungi. These molecules include Aspirochlorine, Aflatoxin B1, Alpha-Cyclopiazonic acid, Sporogen, Asperfuran, Aspergillomarasmine A, Maltoryzine, Kojic acid, Aflatrem and Ethyl 3-nitropropionic acid, arranged in the descending order of their docking score. Aspirochlorine exhibited the docking score of – 7.18 Kcal/mole, higher than presently used drug Chloroquine (-6.2930522 Kcal/mol) and out of ten ligands studied four has docking score higher than chloroquine. These natural bioactive compounds could be tested for their ability to inhibit viral growth <i>in- vitro</i> and <i>in-vivo</i>.<b> </b></p>

Synthesis and biological evaluation of 2-(2-methyl-1H-pyrrol-3-yl)-2-oxo-N-(pyridine-3-yl) acetamide derivatives: in vitro α-glucosidase inhibition, and kinetic and molecular docking study

2019 ◽  
Vol 74 (5) ◽  
pp. 1583-1596
Author(s):  
Tadesse Bekele Tafesse ◽  
Ebrahim Saeedian Moghadam ◽  
Mohammed Hussen Bule ◽  
Neda Abadian ◽  
Mohammad Abdollahi ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Docking Study ◽  
Biological Evaluation ◽  
Molecular Docking Study ◽  
Synthesis And Biological Evaluation

scholarly journals Comparative Study of Piper sylvaticum Roxb. Leaves and Stems for Anxiolytic and Antioxidant Properties Through In Vivo, In Vitro, and In Silico Approaches

Biomedicines ◽  
2020 ◽  
Vol 8 (4) ◽  
pp. 68 ◽  
Author(s):  
Md. Adnan ◽  
Md. Nazim Uddin Chy ◽  
A.T.M. Mostafa Kamal ◽  
Md Obyedul Kalam Azad ◽  
Kazi Asfak Ahmed Chowdhury ◽  
...  
Keyword(s):  
Molecular Docking ◽  
In Silico ◽  
Antioxidant Activities ◽  
Antioxidant Properties ◽  
Reducing Power ◽  
Docking Study ◽  
Molecular Docking Study ◽  
Dose Dependent

Piper sylvaticum Roxb. is traditionally used by the indigenous people of tropical and subtropical countries like Bangladesh, India, and China for relieving the common cold or a variety of chronic diseases, such as asthma, chronic coughing, piles, rheumatic pain, headaches, wounds, tuberculosis, indigestion, and dyspepsia. This study tested anxiolytic and antioxidant activities by in vivo, in vitro, and in silico experiments for the metabolites extracted (methanol) from the leaves and stems of P. sylvaticum (MEPSL and MEPSS). During the anxiolytic evaluation analyzed by elevated plus maze and hole board tests, MEPSL and MEPSS (200 and 400 mg/kg, body weight) exhibited a significant and dose-dependent reduction of anxiety-like behavior in mice. Similarly, mice treated with MEPSL and MEPSS demonstrated dose-dependent increases in locomotion and CNS simulative effects in open field test. In addition, both extracts (MEPSL and MEPSS) also showed moderate antioxidant activities in DPPH scavenging and ferric reducing power assays compared to the standard, ascorbic acid. In parallel, previously isolated bioactive compounds from this plant were documented and subjected to a molecular docking study to correlate them with the pharmacological outcomes. The selected four major phytocompounds displayed favorable binding affinities to potassium channel and xanthine oxidoreductase enzyme targets in molecular docking experiments. Overall, P. sylvaticum is bioactive, as is evident through experimental and computational analysis. Further experiments are necessary to evaluate purified novel compounds for the clinical evaluation.

Potential Bioactive glycosylated flavonoids as SARS-CoV-2 Main protease Inhibitors: A molecular Docking Study

2020 ◽  
Author(s):  
sabri ahmed cherrak ◽  
merzouk hafida ◽  
mokhtari soulimane nassima
Keyword(s):  
Molecular Docking ◽  
Data Bank ◽  
Docking Study ◽  
Docking Studies ◽  
Molecular Docking Study ◽  
Chemical Structures ◽  
In Vivo Experiments ◽  
Main Protease

A novel (COVID-19) responsible of acute respiratory infection closely related to SARS-CoV has recently emerged. So far there is no consensus for drug treatment to stop the spread of the virus. Discovery of a drug that would limit the virus expansion is one of the biggest challenges faced by the humanity in the last decades. In this perspective, testing existing drugs as inhibitors of the main COVID-19 protease is a good approach.Among natural phenolic compounds found in plants, fruit, and vegetables; flavonoids are the most abundant. Flavonoids, especially in their glycosylated forms, display a number of physiological activities, which makes them interesting to investigate as antiviral molecules.The flavonoids chemical structures were downloaded from PubChem and protease structure 6lu7 was from the Protein Data Bank site. Molecular docking study was performed using AutoDock Vina. Among the tested molecules Quercetin-3-O-rhamnoside showed the highest binding affinity (-9,7 kcal/mol). Docking studies showed that glycosylated flavonoids are good inhibitors for the covid-19 protease and could be further investigated by in vitro and in vivo experiments for further validation.

Sign in / Sign up

Export Citation Format

Share Document