Molecular docking and in silico studies of the physicochemical properties of potential inhibitors for the phosphotransferase system of Streptococcus mutans

Background: From the fruits and seeds of the species of Pterodon, it is possible to obtain two main products: the essential oil and oleoresin. In oleoresin, numerous vouacapan compounds have been demonstrated to have biological potential, including insecticidal activity. Objective: In silico studies were performed to identify potential candidates for natural insecticides among the vouacapans present in the genus Pterodon. Materials and Methods: Molecular docking and molecular dynamics studies were performed to analyze the interaction of vouacapan compounds with acetylcholinesterase of Drosophila melanogaster. Pharmacokinetic parameters regarding physicochemical properties, plasma protein binding, and activity in the central nervous system were evaluated. The toxicological properties of the selected molecules were predicted using Malathion as the reference compound. Results: 6α,7β-dimethoxivouacapan-17-ene (15) showed a high number of interactions and scores in molecular docking studies. This result suggests that this compound exhibits an inhibitory activity of the enzyme acetylcholinesterase. Regarding physicochemical properties, this compound showed the best results, besides presenting low cutaneous permeability values, suggesting null absorption. Molecular dynamics studies demonstrated few conformational changes in the structure of the complex formed by compound 4 and acetylcholinesterase enzyme throughout the simulation time. Conclusion: It was determined that compound 4 (vouacapan 6α,7β,17β,19-tetraol) is an excellent candidate for usage as a natural insecticide.

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The Molecular Docking of Flavonoids Isolated from Daucus carota as a Dual Inhibitor of MDM2 and MDMX

Recent Patents on Anti-Cancer Drug Discovery ◽

10.2174/1574892815666200226112506 ◽

2020 ◽

Vol 15 (2) ◽

pp. 154-164 ◽

Cited By ~ 1

Author(s):

Ijaz Muhammad ◽

Noor Rahman ◽

Gul E. Nayab ◽

Sadaf Niaz ◽

Mohibullah Shah ◽

...

Keyword(s):

Molecular Docking ◽

Cancer Therapy ◽

Natural Product ◽

Signaling Pathway ◽

In Silico ◽

P53 Protein ◽

Dual Inhibitor ◽

P53 Signaling ◽

In Silico Studies ◽

P53 Signaling Pathway

Background: Cancer is characterized by overexpression of p53 associated proteins, which down-regulate P53 signaling pathway. In cancer therapy, p53 activity can be restored by inhibiting the interaction of MDMX (2N0W) and MDM2 (4JGR) proteins with P53 protein. Objective: In the current, study in silico approaches were adapted to use a natural product as a source of cancer therapy. Methods: In the current study in silico approaches were adapted to use a natural product as a source of cancer therapy. For in silico studies, Chemdraw and Molecular Operating Environment were used for structure drawing and molecular docking, respectively. Flavonoids isolated from D. carota were docked with cancerous proteins. Result: Based on the docking score analysis, we found that compound 7 was the potent inhibitor of both cancerous proteins and can be used as a potent molecule for inhibition of 2N0W and 4JGR interaction with p53. Conclusion: Thus the compound 7 can be used for the revival of p53 signaling pathway function however, intensive in vitro and in vivo experiments are required to prove the in silico analysis.

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Amino Acids Sequence-based Analysis of Arginine Deiminase from Different Prokaryotic Organisms: An In Silico Approach

Recent Patents on Biotechnology ◽

10.2174/1872208314666200324114441 ◽

2020 ◽

Vol 14 (3) ◽

pp. 235-246

Author(s):

Sara Abdollahi ◽

Mohammad H. Morowvat ◽

Amir Savardashtaki ◽

Cambyz Irajie ◽

Sohrab Najafipour ◽

...

Keyword(s):

Amino Acid ◽

Physicochemical Properties ◽

Sequence Alignment ◽

Multiple Sequence Alignment ◽

In Silico ◽

Bacterial Species ◽

Arginine Deiminase ◽

Antitumor Effects ◽

Multiple Sequence ◽

In Silico Studies

Background: Arginine deiminase is a bacterial enzyme, which degrades L-arginine. Some human cancers such as hepatocellular carcinoma (HCC) and melanoma are auxotrophic for arginine. Therefore, PEGylated arginine deiminase (ADI-PEG20) is a good anticancer candidate with antitumor effects. It causes local depletion of L-arginine and growth inhibition in arginineauxotrophic tumor cells. The FDA and EMA have granted orphan status to this drug. Some recently published patents have dealt with this enzyme or its PEGylated form. Objective: Due to increasing attention to it, we aimed to evaluate and compare 30 arginine deiminase proteins from different bacterial species through in silico analysis. Methods: The exploited analyses included the investigation of physicochemical properties, multiple sequence alignment (MSA), motif, superfamily, phylogenetic and 3D comparative analyses of arginine deiminase proteins thorough various bioinformatics tools. Results: The most abundant amino acid in the arginine deiminase proteins is leucine (10.13%) while the least amino acid ratio is cysteine (0.98%). Multiple sequence alignment showed 47 conserved patterns between 30 arginine deiminase amino acid sequences. The results of sequence homology among 30 different groups of arginine deiminase enzymes revealed that all the studied sequences located in amidinotransferase superfamily. Based on the phylogenetic analysis, two major clusters were identified. Considering the results of various in silico studies; we selected the five best candidates for further investigations. The 3D structures of the best five arginine deiminase proteins were generated by the I-TASSER server and PyMOL. The RAMPAGE analysis revealed that 81.4%-91.4%, of the selected sequences, were located in the favored region of arginine deiminase proteins. Conclusion: The results of this study shed light on the basic physicochemical properties of thirty major arginine deiminase sequences. The obtained data could be employed for further in vivo and clinical studies and also for developing the related therapeutic enzymes.

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Enzymatic Textile Dyes Decolorization by In vitro and In silico Studies

Recent Patents on Biotechnology ◽

10.2174/1872208313666190625123847 ◽

2019 ◽

Vol 13 (4) ◽

pp. 268-276

Author(s):

Sridevi Ayla ◽

Monika Kallubai ◽

Suvarnalatha Devi Pallipati ◽

Golla Narasimha

Keyword(s):

Molecular Docking ◽

In Silico ◽

Docking Studies ◽

Textile Dyes ◽

Crude Enzyme ◽

Eastern Ghats ◽

Textile Dye ◽

Phanerochaete Sordida ◽

Molecular Docking Studies ◽

In Silico Studies

Background:Laccase, a multicopper oxidoreductase (EC: 1.10.3.2), is a widely used enzyme in bioremediation of textile dye effluents. Fungal Laccase is preferably used as a remediating agent in the treatment and transformation of toxic organic pollutants. In this study, crude laccase from a basidiomycetes fungus, Phanerochaete sordida, was able to decolorize azo, antroquinone and indigoid dyes. In addition, interactions between dyes and enzyme were analysed using molecular docking studies.Methods:In this work, a white rot basidiomycete’s fungus, Phanerochaete sordida, was selected from forest soil isolates of Eastern Ghats, and Tirumala and lignolytic enzymes production was assayed after 7 days of incubation. The crude enzyme was checked for decolourisation of various synthetic textile dyes (Vat Brown, Acid Blue, Indigo, Reactive Blue and Reactive Black). Molecular docking studies were done using Autodock-4.2 to understand the interactions between dyes and enzymes.Results:Highest decolourisation efficiency was achieved with the crude enzyme in case of vat brown whereas the lowest decolourisation efficiency was achieved in Reactive blue decolourisation. Similar results were observed in their binding affinity with lignin peroxidase of Phanerochaete chrysosporium through molecular docking approach.Conclusion:Thus, experimental results and subsequent in silico validation involving an advanced remediation approach would be useful to reduce time and cost in other similar experiments.

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2-(Chloromethyl)-3-phenylquinazolin-4(3H)-ones as potent anticancer agents; cytotoxicity, molecular docking and in silico studies

Journal of the Iranian Chemical Society ◽

10.1007/s13738-021-02168-1 ◽

2021 ◽

Author(s):

Leila Emami ◽

Zeinab Faghih ◽

Soghra Khabnadideh ◽

Zahra Rezaei ◽

Razieh Sabet ◽

...

Keyword(s):

Molecular Docking ◽

Anticancer Agents ◽

In Silico ◽

In Silico Studies

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IN SILICO STUDIES ON FUNCTIONALIZED AZAGLYCINE DERIVATIVES CONTAINING 2, 4-THIAZOLIDINEDIONE SCAFFOLD ON MULTIPLE TARGETS

International Journal of Pharmacy and Pharmaceutical Sciences ◽

10.22159/ijpps.2017v9i8.19835 ◽

2017 ◽

Vol 9 (8) ◽

pp. 209 ◽

Cited By ~ 4

Author(s):

Arifa Begum ◽

Shaheen Begum ◽

Prasad Kvsrg ◽

Bharathi K.

Keyword(s):

Molecular Docking ◽

Oral Bioavailability ◽

In Silico ◽

Viral Infections ◽

Target Prediction ◽

Docking Studies ◽

Antidiabetic Activity ◽

Molecular Docking Studies ◽

In Silico Studies ◽

Glycine Derivative

Objective: The 2, 4-thiazolidinedione containing compounds could lead to most promising scaffolds with higher efficiency toward the targets recognized for its antidiabetic activity when combined with azaglycine moiety. The objective of the present work was to merge functionalized aza glycines with 2, 4-thiazolidinediones, perform in silico evaluation by molecular properties prediction and undertake the molecular docking studies with targets relevant to diabetes, bacterial and viral infections using Swiss Dock programme for unraveling the target identification which can be used for further designing.Methods: (i) In silico studies were performed using Molinspiration online tool, Swiss ADME website and Swiss Target Prediction websites to compute the physicochemical descriptors, oral bioavailability and brain penetration. (ii) Molecular docking studies were performed using Swiss Dock web service for enumeration of binding affinities and assess their biological potentiality.Results: The results predicted good drug likeness, solubility, permeability and oral bioavailability for the compounds. All the compounds showed good docking scores as compared to the reference drugs. The N-oleoyl functionalized aza glycine derivative demonstrated superior binding properties towards all the studied target reference proteins, suggesting its significance in pharmacological actions.Conclusion: The binding interactions observed in the molecular docking studies suggest good binding affinity of the oleoyl functionalized aza glycine derivative, indicating that this derivative would be a promising lead for further investigations of anti-viral, anti-inflammatory and anti-diabetic activities.

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Reverse Docking, Molecular Docking, Absorption, Distribution, and Toxicity Prediction of Artemisinin as an Anti-diabetic Candidate

Molekul ◽

10.20884/1.jm.2020.15.2.579 ◽

2020 ◽

Vol 15 (2) ◽

pp. 88

Author(s):

Ruswanto Ruswanto ◽

Richa Mardianingrum ◽

Siswandono Siswandono ◽

Dini Kesuma

Keyword(s):

Molecular Docking ◽

Aldose Reductase ◽

Glucose Concentration ◽

In Silico ◽

Reductase Activity ◽

Polyol Pathway ◽

Toxicity Prediction ◽

In Silico Studies

Aldose reductase is an enzyme that catalyzes one of the steps in the sorbitol (polyol) pathway that is responsible for fructose formation from glucose. In diabetes, aldose reductase activity increases as the glucose concentration increases. The purpose of this research was to identify and develop the use of artemisinin as an anti-diabetic candidate through in silico studies, including reverse docking, receptor analysis, molecular docking, drug scan, absorption, and distributions and toxicity prediction of artemisinin. Based on the results, we conclude that artemisinin can be used as an anti-diabetic candidate through inhibition of aldose reductase

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In silico drug design: development of new pyrimidine-based benzo-thiazole derivatives, selective for CDK2

Letters in Drug Design & Discovery ◽

10.2174/1570180818666210421134819 ◽

2021 ◽

Vol 18 ◽

Author(s):

Rania Kasmi ◽

Larbi Elmchichi ◽

Abdellah El Aissouq ◽

Mohammed Bouachrine ◽

Abdelkrim Ouammou

Keyword(s):

Colon Cancer ◽

Molecular Docking ◽

In Silico ◽

3D Qsar ◽

Bioactive Molecules ◽

Cancer Drugs ◽

Qsar Studies ◽

Benzothiazole Derivatives ◽

Docking Approach ◽

Potential Inhibitors

Backgroud: Kinases are proteins that control many biological functions. They are involved in cellular regulation, and many of them are deregulated in cancer proliferation. The evidence of this deregulation in many pathologies served as the origin of kinases as a therapeutic class and constitutes the motive that leads numerous teams to search for inhibitors of these targets. Objective: Based on 3D-QSAR studies and the molecular docking approach, we have developed new potential inhibitors that could be optimized and transformed into colon cancer drugs. Objective: Based on 3D-QSAR studies and the molecular docking approach, we have developed new potential inhibitors that could be optimized and transformed into colon cancer drugs. Method: To design new bioactive molecules and study their interactions with the cyclin-depend kinase type 2 (CDK2) enzyme, we used two virtual screening methods: 3D-QSAR modeling and molecular docking on a series of 28 pyrimidine-based benzothiazole derivatives. Results: To develop models (3D QSAR) we used CoMFA and CoMSIA techniques using SYBYL-X2.0 molecular modeling software. The statistical parameters reveal that the good CoMFA model displays (Q²= 0.587; R²= 0.895) and that of CoMSIA displays (Q²= 0.552; R²= 0.768) which are considered to be very good internal prediction values, while an external validation of a test series of 5 compounds not included in the model development series gives R²test values of 0.56 for CoMFA and R²test values of 0.51 for CoMSIA. The molecular docking approach with AutoDockTools-1.5.6 is introduced in this work to enrich the interpretations extracted from the CoMFA and CoMSIA contour maps, and to provide an in silico research method for the most favorable mode of interaction of an inhibitor within its receptor (CDK2). Conclusion: We have constructed and validated a quantitative 3D model of structure-activity relation-ships of pyrimidine-based benzothiazole derivatives as CDK2 inhibitors. This model allows us to identify the nature and position of the groups that enhance the activity, giving us directions to discover new, more powerful molecules in a limited time.

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