Virtual molecular docking study of some novel carboxamide series as new anti-tubercular agents

A virtual docking simulation study was performed on thirty-five newly discovered compounds of N-(2-phenoxy) ethyl imidazo[1,2-a] pyridine-3-carboxamide (IPA), to explore their theoretical binding energy and pose with the active sites of the Mycobacterium tuberculosis target (DNA gyrase). The chemical structures of the compounds were drawn correctly with ChemDraw Ultra software, and then geometrically optimized at DFT level of theory with Spartan 14 software package. Consequently, the docking analysis was carried out using Molegro Virtual Docker (MVD). Five complexes (Complex 5, 24, 25, 33 and 35) with high binding energy were selected to examine their binding pose with the active sites of the protein. The docking results suggested a good MolDock score (≥ -90 kcal/mol) and Protein-Ligand ANT System (PLANTS) score (≥ -60 kcal/mol) which depicted that the compounds can efficiently bind with the active sites of the target. However, compound 5 has the best binding pose with the MolDock score of -140.476 kcal/mol which formed three hydrogen bond interactions with the Gln 538, Ala 531, and Ala 533 amino acid residues. This research gives a firsthand theoretical knowledge to improve the binding efficiency of these compounds with the target.

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Synthesis of 2-(4-hydroxyphenyl)ethyl 3,4,5-Trihydroxybenzoate and Its Inhibitory Effect on Sucrase and Maltase

Processes ◽

10.3390/pr8121603 ◽

2020 ◽

Vol 8 (12) ◽

pp. 1603

Author(s):

Wen-Tai Li ◽

Yu-Hsuan Chuang ◽

Jiahn-Haur Liao ◽

Jung-Feng Hsieh

Keyword(s):

Active Site ◽

Docking Study ◽

Competitive Inhibitor ◽

Inhibitory Effect ◽

Kinetics Study ◽

Amino Acid Residues ◽

Inhibition Kinetics ◽

Molecular Docking Study ◽

Hydrogen Bond Interactions ◽

Glucosidase Inhibitors

We report on the synthesis of an active component, 2-(4-hydroxyphenyl)ethyl 3,4,5-trihydroxybenzoate (HETB), from Rhodiola crenulata. Subsequent analysis revealed that HETB exhibits α-glucosidase inhibitory activities on maltase and sucrase, with potency exceeding that of the known α-glucosidase inhibitors (voglibose and acarbose). An inhibition kinetics study revealed that HETB, acarbose, and voglibose bind to maltase and sucrase, and HETB was shown to be a strong competitive inhibitor of maltase and sucrase. In a molecular docking study based on the crystal structure of α-glucosidase from Saccharomyces cerevisiae, we revealed the HETB binding in the active site of maltase via hydrogen-bond interactions with five amino acid residues: Ser 240, Asp 242, Glu 277, Arg 315, and Asn 350. For HETB docked to the sucrase active site, seven hydrogen bonds (with Asn 114, Glu 148, Gln 201, Asn 228, Gln 381, Ile 383, and Ser 412) were shown.

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Effects Of Herbicides And Fungicides On The Soil Chitinolytic Activity. A Molecular Docking Approach

Ecological Chemistry and Engineering S ◽

10.1515/eces-2015-0025 ◽

2015 ◽

Vol 22 (3) ◽

pp. 439-450

Author(s):

Diana Larisa Vlădoiu ◽

Marioara Nicoleta Filimon ◽

Vasile Ostafe ◽

Adriana Isvoran

Keyword(s):

Molecular Docking ◽

Binding Energy ◽

Active Sites ◽

Soil Microorganisms ◽

Docking Study ◽

Chitinolytic Activity ◽

Molecular Docking Study ◽

Receptor Ligand ◽

Docking Approach ◽

Inhibitory Potential

Abstract A molecular docking study was undertaken using the programs SwissDock and PatchDock to assess the interactions of the bacterial chitinases belonging to the GH18 and GH19 families with two herbicides (chlorsulfuron and nicosulfuron) and two fungicides (difenoconazole and drazoxolon). Both molecular docking programs predict that all considered pesticides bind to the active sites of chitinases produced by soil microorganisms. There are correlations for predicted binding energy values for receptor-ligand complexes obtained using the two programs consolidating the prediction of the chitinases-pesticides interactions. The interactions of chitinases with pesticides involve the same residues as their interactions with known inhibitors suggesting the inhibitory potential of pesticides. Pesticides interact stronger with chitinases belonging to the GH18 family, their active sites reflecting higher polarity than those of the GH19 chitinases. Also, herbicides reveal a higher inhibitory potential to bacterial chitinases than fungicides.

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Lead Molecules as Novel Aromatase Inhibitors: In Silico De Novo Designing and Binding Affinity Studies

Letters in Drug Design & Discovery ◽

10.2174/1570180816666190703152659 ◽

2020 ◽

Vol 17 (5) ◽

pp. 655-665 ◽

Cited By ~ 1

Author(s):

Laxmi Banjare ◽

Sant Kumar Verma ◽

Akhlesh Kumar Jain ◽

Suresh Thareja

Keyword(s):

Drug Design ◽

Aromatase Inhibitors ◽

De Novo ◽

Scale Up ◽

Geometry Optimization ◽

Docking Study ◽

Molecular Docking Study ◽

De Novo Drug Design ◽

Molegro Virtual Docker ◽

Estrogen Production

Background:Aromatase inhibitors emerged as a pivotal moiety to selectively block estrogen production, prevention and treatment of tumour growth in breast cancer. De novo drug design is an alternative approach to blind virtual screening for successful designing of the novel molecule against various therapeutic targets.Objective:In the present study, we have explored the de novo approach to design novel aromatase inhibitors.Method:The e-LEA3D, a computational-aided drug design web server was used to design novel drug-like candidates against the target aromatase. For drug-likeness ADME parameters (molecular weight, H-bond acceptors, H-bond donors, LogP and number of rotatable bonds) of designed molecules were calculated in TSAR software package, geometry optimization and energy minimization was accomplished using Chem Office. Further, molecular docking study was performed in Molegro Virtual Docker (MVD).Results:Among 17 generated molecules using the de novo pathway, 13 molecules passed the Lipinski filter pertaining to their bioavailability characteristics. De novo designed molecules with drug-likeness were further docked into the mapped active site of aromatase to scale up their affinity and binding fitness with the target. Among de novo fabricated drug like candidates (1-13), two molecules (5, 6) exhibited higher affinity with aromatase in terms of MolDock score (-150.650, -172.680 Kcal/mol, respectively) while molecule 8 showed lowest target affinity (-85.588 Kcal/mol).Conclusion:The binding patterns of lead molecules (5, 6) could be used as a pharmacophore for medicinal chemists to explore these molecules for their aromatase inhibitory potential.

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Molecular Docking Study of the Potential Relevance of the Natural Compounds Isoflavone and Myricetin to COVID-19

International Journal Bioautomation ◽

10.7546/ijba.2021.25.3.000796 ◽

2021 ◽

Vol 25 (3) ◽

pp. 271-282

Author(s):

Didik Priyandoko ◽

◽

Wahyu Widowati ◽

Mawar Subangkit ◽

Diana Jasaputra ◽

...

Keyword(s):

Molecular Docking ◽

Severe Acute Respiratory Syndrome ◽

Active Sites ◽

Docking Study ◽

Binding Mode ◽

Molecular Docking Study ◽

Wuhan City ◽

The World ◽

Novel Coronavirus ◽

Proteins Interactions

The 2019 novel coronavirus (2019-nCoV) or severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread rapidly from its origin in Wuhan City, Hubei Province, China, to the rest of the world. The efficacy of herbal treatment in the control of contagious disease was demonstrated during the 2003 outbreak of severe acute respiratory syndrome (SARS). Natural compound used for this study were isoflavone and myricetin. Molecular docking was performed to analyze binding mode of the compounds towards 12 proteins related to COVID-19. The prediction shows that isoflavone and myricetin have moderate probability of antiviral activity. All of the docked compounds occupied the active sites of the proteins related to COVID-19. Based on QSAR and molecular docking, interactions were predicted with 10 out of 12 potential COVID-19 proteins for myricetin and with 9 out of 12 proteins interactions for isoflavone. A potential disease alleviating action is suggested for isoflavone and myricetin in the context of COVID-19 infection.

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Synthesis, Anti-Inflammatory Activity, and In Silico Study of Novel Diclofenac and Isatin Conjugates

International Journal of Medicinal Chemistry ◽

10.1155/2018/9139786 ◽

2018 ◽

Vol 2018 ◽

pp. 1-11

Author(s):

Musab Mohamed Ibrahim ◽

Tilal Elsaman ◽

Mosab Yahya Al-Nour

Keyword(s):

Virtual Screening ◽

Condensation Reaction ◽

Docking Study ◽

Positive Control ◽

Inflammatory Activity ◽

Molecular Docking Study ◽

Design Synthesis ◽

Chemical Structures ◽

Anti Inflammatory

The design, synthesis, and development of novel non-steroidal anti-inflammatory drugs (NSAIDs) with better activity and lower side effects are respectable area of research. Novel Diclofenac Schiff’s bases (M1, M2, M4, M7, and M8) were designed and synthesized, and their respective chemical structures were deduced using various spectral tools (IR, 1H NMR, 13C NMR, and MS). The compounds were synthesized via Schiff’s condensation reaction and their anti-inflammatory activity was investigated applying the Carrageenan-induced paw edema model against Diclofenac as positive control. Percentage inhibition of edema indicated that all compounds were exhibiting a comparable anti-inflammatory activity as Diclofenac. Moreover, the anti-inflammatory activity was supported via virtual screening using molecular docking study. Interestingly compound M2 showed the highest in vivo activity (61.32% inhibition) when compared to standard Diclofenac (51.36% inhibition) as well as the best binding energy score (-10.765) and the virtual screening docking score (-12.142).

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Identification of Potential Inhibitors from Pyriproxyfen with Insecticidal Activity by Virtual Screening

Pharmaceuticals ◽

10.3390/ph12010020 ◽

2019 ◽

Vol 12 (1) ◽

pp. 20 ◽

Cited By ~ 9

Author(s):

Ryan Ramos ◽

Josivan Costa ◽

Rai Silva ◽

Glauber da Costa ◽

Alex Rodrigues ◽

...

Keyword(s):

Virtual Screening ◽

Binding Free Energy ◽

Structural Similarity ◽

Docking Study ◽

Molecular Docking Study ◽

Chemical Structures ◽

Biological Insecticide ◽

Pass Online ◽

Acetylcholinesterase Enzyme ◽

Potential Inhibitors

Aedes aegypti is the main vector of dengue fever transmission, yellow fever, Zika, and chikungunya in tropical and subtropical regions and it is considered to cause health risks to millions of people in the world. In this study, we search to obtain new molecules with insecticidal potential against Ae. aegypti via virtual screening. Pyriproxyfen was chosen as a template compound to search molecules in the database Zinc_Natural_Stock (ZNSt) with structural similarity using ROCS (rapid overlay of chemical structures) and EON (electrostatic similarity) software, and in the final search, the top 100 were selected. Subsequently, in silico pharmacokinetic and toxicological properties were determined resulting in a total of 14 molecules, and these were submitted to the PASS online server for the prediction of biological insecticide and acetylcholinesterase activities, and only two selected molecules followed for the molecular docking study to evaluate the binding free energy and interaction mode. After these procedures were performed, toxicity risk assessment such as LD50 values in mg/kg and toxicity class using the PROTOX online server, were undertaken. Molecule ZINC00001624 presented potential for inhibition for the acetylcholinesterase enzyme (insect and human) with a binding affinity value of −10.5 and −10.3 kcal/mol, respectively. The interaction with the juvenile hormone was −11.4 kcal/mol for the molecule ZINC00001021. Molecules ZINC00001021 and ZINC00001624 had excellent predictions in all the steps of the study and may be indicated as the most promising molecules resulting from the virtual screening of new insecticidal agents.

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Molecular docking study of the phytol and its derivatives against COX-2 induced inflammation: A combined density functional study

Recent Research in Science and Technology ◽

10.25081/rrst.2020.12.6083 ◽

2020 ◽

pp. 1-5

Author(s):

Muhammad Torequl Islam ◽

Pranta Ray ◽

Abul Bashar Ripon Khalipha ◽

SM Hafiz Hassan ◽

Md. Roich Khan ◽

...

Keyword(s):

Molecular Docking ◽

Binding Energy ◽

Density Functional ◽

Chemical Reactivity ◽

Docking Study ◽

Functional Study ◽

Molecular Docking Study ◽

Study Results ◽

Homo And Lumo ◽

Cox 2

This study aimed to determine the activity of PYT and its derivatives against COX-2, including 5IKR protein induced inflammation by using the computational tools. PYT and its derivatives have been designed by utilizing density functional theory (DFT) and the performance of the drugs was also evaluated by molecular docking study. Results suggest that the NH2 derivative of PYT (D-NH2) showed binding energy -6.4 (Kcal/mol) with protein 5IKR of COX-2 compared to the main drug (D) that showed binding energy -5.1 (Kcal/mol) with the same protein. HOMO and LUMO energy values were also calculated to determine the chemical reactivity of all the modified drugs. Non-covalent interactions of PYT and its derivatives were essential in improving the performance. In conclusion, D-NH2 showed better preference in inhibiting to the protein 5IKR of COX-2 compared to other modified drugs and it can be claimed that D-NH2 will be the best conformer for COX-2 induced inflammation.

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MOLECULAR DOCKING STUDY TO IDENTIFY POTENTIAL INHIBITOR OF COVID-19 MAIN PROTEASE ENZYME: AN IN-SILICO APPROACH

10.26434/chemrxiv.12170904 ◽

2020 ◽

Author(s):

Anurag Agrawal ◽

Nem Kumar Jain ◽

Neeraj Kumar ◽

Giriraj T Kulkarni

Keyword(s):

Molecular Docking ◽

Active Site ◽

Docking Study ◽

Molecular Docking Study ◽

Potential Threat ◽

Discovery Studio ◽

Chemical Structures ◽

Potential Inhibitor ◽

Protease Enzyme ◽

Main Protease

This study belongs to identification of suitable COVID-19 inhibitors<br><div><br></div><div>Coronavirus became pandemic very soon and is a potential threat to human lives across the globe. No approved drug is currently available therefore an urgent need has been developed for any antiviral therapy for COVID-19. For the molecular docking study, ten herbal molecules have been included in the current study. The three-dimensional chemical structures of molecules were prepared through ChemSketch 2015 freeware. Molecular docking study was performed using AutoDock 4.2 simulator and Discovery studio 4.5 was employed to predict the active site of target enzyme. Result indicated that all-natural molecules found in the active site of enzyme after molecular docking. Oxyacanthine and Hypericin (-10.990 and -9.05 and kcal/mol respectively) have shown good binding efficacy among others but Oxyacanthine was the only natural product which made some of necessary interactions with residues in the enzyme require for target inhibition. Therefore Oxyacanthine may be considered to be potential inhibitor of main protease enzyme of virus but need to be explored for further drug development process. <br></div>

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MOLECULAR DOCKING STUDY OF NATURALLY OCCURRING COMPOUNDS AS INHIBITORS OF COVID -19

Asian Journal of Pharmaceutical and Clinical Research ◽

10.22159/ajpcr.2022.v15i1.43121 ◽

2021 ◽

pp. 69-71

Author(s):

SREEDEVI A ◽

MALAR RETNA A ◽

ROBIN KUMAR SAMUEL

Keyword(s):

Molecular Docking ◽

Binding Energy ◽

Docking Study ◽

Molecular Docking Study ◽

Discovery Studio ◽

Naturally Occurring ◽

Short Period ◽

The Right ◽

Native Ligand ◽

Made In

Objectives: The worldwide spread of COVID-19 is an emergent issue to be tackled. Currently, several works in various field have been made in rather short period. The present study aimed to assess bioactive compounds found in medicinal plants as potential COVID-19 Mpro inhibitors using molecular docking study. Methods: The docking analyses were performed by using Autodock, Discovery Studio Visualiser and Igemdock. Results: The binding energy obtained from the docking of 6LU7 with native ligand cupressuflavone is -8.9 kcal/mol. Conclusion: These findings will provide the opportunities to identify the right drug to combat COVID-19.

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In silico docking analysis of selective bioactive compounds of Phyllanthus acidusaqueousfruit extractagainst MAPK1

Biomedicine ◽

10.51248/.v41i2.1038 ◽

2021 ◽

Vol 41 (2) ◽

pp. 349-357

Author(s):

E. Padmini ◽

M. Kavitha

Keyword(s):

Binding Energy ◽

Cell Survival ◽

Bioactive Compounds ◽

In Silico ◽

Docking Study ◽

Mitogen Activated Protein Kinase ◽

Molecular Docking Study ◽

Ligand Complex ◽

In Silico Docking ◽

Methyl Prednisolone

Introduction and Aim: Phyllanthus acidus L.Skeels (Family: Phyllanthaceae) or Star Gooseberry which bears small, edible, juicy, sour, yellow berries fruit is known as a “liver tonic” in ayurvedic medicine. However, the behavior of the plant fruit or its constituents in cell apoptosis/cell survival is unknown. Hence, the purpose of thepresent study was to perform an in silico docking of selective bioactive compounds of aqueous extract of fruit of P.acidus (PAFAE) against MAPK1. Mitogen activated protein kinase is a family of serine threonine specific protein kinases- MAPK1/ERK1/2, JNK1-3, p38MAPK and ERK5.Activation ofMAPK1 promotes cell survival in certain tissues by inhibiting proapoptotic proteins and by stimulating anti apoptotic factors. Methodology: In silico docking studies was carried out using bioinformatics tools.The active compounds (Trihomovitamin D3; 2Z,6Z,8Z,12E Hexadecatetraenoic acid, Methyl prednisolone, Hydroxysalmeterol and Tridesacetoxykhivorin) ofP.acidus aqueous fruit extract were docked against MAPK1 resulting in receptor-ligand complex. Results: The binding energy is correlated with the probability of affinity and stable bound between ligand and its receptor. Conclusion: The molecular docking study of selective bioactive compounds of PAFAE with MAPK1 protein revealed that Tridesacetoxykhivorinand Methyl Prednisolone, is having good interaction in favorable pose with MAPK1 as shownfrom theireffective binding energy(-7.79kcal/mol and -7.19 kcal/mol), strong bond length and interactions with active site of MAPK1.

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