In Silico Structural, Virtual Screening and Docking Studies of Human Cytochrome P450 2A7 Protein

Background: Postprandial hyperglycemia considered to be a major risk factor for cerebrovascular complications. Objective: The current study was designed to elucidate the beneficial role of voglibose via in-silico in vitro to in-vivo studies in improving the postprandial glycaemic state by protection against strokeprone type 2 diabetes. Material and Methods: In-Silico molecular docking and virtual screening were carried out with the help of iGEMDOCK+ Pymol+docking software and Protein Drug Bank database (PDB). Based on the results of docking studies, in-vivo investigation was carried out for possible neuroprotective action. T2DM was induced by a single injection of streptozotocin (90mg/kg, i.v.) to neonates. Six weeks after induction, voglibose was administered at the dose of 10mg/kg p.o. for two weeks. After eight weeks, diabetic rats were subjected to middle cerebral artery occlusion, and after 72 hours of surgery, neurological deficits were determined. The blood was collected for the determination of serum glucose, CK-MB, LDH and lipid levels. Brains were excised for determination of brain infarct volume, brain hemisphere weight difference, Na+-K+ ATPase activity, ROS parameters, NO levels, and aldose reductase activity. Results: In-silico docking studies showed good docking binding score for stroke associated proteins, which possibly hypotheses neuroprotective action of voglibose in stroke. In the present in-vivo study, pre-treatment with voglibose showed a significant decrease (p<0.05) in serum glucose and lipid levels. Voglibose has shown significant (p<0.05) reduction in neurological score, brain infarct volume, the difference in brain hemisphere weight. On biochemical evaluation, treatment with voglibose produced significant (p<0.05) decrease in CK-MB, LDH, and NO levels in blood and reduction in Na+-K+ ATPase, oxidative stress, and aldose reductase activity in brain homogenate. Conclusion: In-silico molecular docking and virtual screening studies and in-vivo studies in MCAo induced stroke, animal model outcomes support the strong anti-stroke signature for possible neuroprotective therapeutics.

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In silico discovery of novel flavonoids as poly ADP ribose polymerase (PARP) inhibitors

Current Computer - Aided Drug Design ◽

10.2174/1573409916666200408082858 ◽

2020 ◽

Vol 16 ◽

Author(s):

Ashish Shah ◽

Ghanshyam Parmar ◽

Avinash Kumar Seth

Keyword(s):

Virtual Screening ◽

In Silico ◽

Synthetic Lethality ◽

Parp Inhibitor ◽

Parp Inhibitors ◽

Docking Studies ◽

Docking Score ◽

Docking Method ◽

Anti Cancer ◽

In Silico Toxicity

Background: The concept of synthetic lethality is emerging field in the treatment of cancer and can be applied for new drug development of cancer as it has been already represented by Poly (ADP-ribose) polymerase (PARPs) inhibitors. Objectives: In this study we performed virtual screening of 329 flavonoids obtained from Naturally Occurring Plant-based Anti-cancer Compound-Activity-Target (NPACT) database to identify novel PARP inhibitors. Materials and methods: Virtual screening carried out using different In Silico methods which includes molecular docking studies, prediction of druglikeness and In Silico toxicity studies. Results: Fifteen out of 329 flavonoids achieved better docking score as compared to rucaparib which is an FDA approved PARP inhibitor. These 15 hits were again rescored using accurate docking mode and drug-likeliness properties were evaluated. Accuracy of docking method was checked using re-docking. Finally NPACT00183 and NPACT00280 were identified as potential PARP inhibitors with docking score of -139.237 and -129.36 respectively. These two flavonoids were also showed no AMES toxicity and no carcinogenicity which was predicted using admetSAR. Conclusion: Our finding suggests that NPACT00183 and NPACT00280 have promising potential to be further explored as PARP inhibitors.

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Screening of cytochrome P450 3A4 inhibitors via in silico and in vitro approaches

RSC Advances ◽

10.1039/c8ra06311g ◽

2018 ◽

Vol 8 (61) ◽

pp. 34783-34792 ◽

Cited By ~ 3

Author(s):

Xiaocong Pang ◽

Baoyue Zhang ◽

Guangyan Mu ◽

Jie Xia ◽

Qian Xiang ◽

...

Keyword(s):

Cytochrome P450 ◽

Virtual Screening ◽

In Silico ◽

Cytochrome P450 3A4 ◽

Important Member ◽

Cyp3a4 Inhibitors

Cytochrome P450 3A4 (CYP3A4) is an important member of the CYP family and responsible for metabolizing a broad range of drugs. It is necessary to establish virtual screening models for predicting CYP3A4 inhibitors.

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Erratum to: Flavonoids as Multi-Target Inhibitors for Proteins Associated with Ebola Virus: In Silico Discovery Using Virtual Screening and Molecular Docking Studies

Interdisciplinary Sciences Computational Life Sciences ◽

10.1007/s12539-015-0125-8 ◽

2015 ◽

Vol 8 (2) ◽

pp. 142-142 ◽

Cited By ~ 1

Author(s):

Utkarsh Raj ◽

Pritish Kumar Varadwaj

Keyword(s):

Molecular Docking ◽

Virtual Screening ◽

In Silico ◽

Ebola Virus ◽

Docking Studies ◽

Molecular Docking Studies

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Identification of Novel Phyto-chemicals from Ocimum basilicum for the Treatment of Parkinson’s Disease using In Silico Approach

Current Computer - Aided Drug Design ◽

10.2174/1573409915666190503113617 ◽

2020 ◽

Vol 16 (4) ◽

pp. 420-434

Author(s):

Nageen Mubashir ◽

Rida Fatima ◽

Sadaf Naeem

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Molecular Docking ◽

Virtual Screening ◽

Active Site ◽

In Silico ◽

Chemical Constituents ◽

Docking Studies ◽

Ocimum Basilicum ◽

Mao B

Background: Parkinson’s disease is characterized by decreased level of dopaminergic neurotransmitters and this decrease is due to the degradation of dopamine by protein Monoamine Oxidase B (MAO-B). In order to treat Parkinson’s disease, MAO-B should be inhibited. Objective: To find out the novel phytochemicals from plant Ocimum basilicum that can inhibit MAO-B by using the in silico methods. Methods: The data of chemical constituents from plant Ocimum basilicum was collected and inhibitory activity of these phytochemicals was then predicted by using the Structure-Based (SB) and Ligand-Based Virtual Screening (LBVS) methods. Molecular docking, one of the common Structure-Based Virtual Screening method, has been used during this search. Traditionally, molecular docking is used to predict the orientation and binding affinity of the ligand within the active site of the protein. Molegro Virtual Docker (MVD) software has been used for this purpose. On the other hand, Random Forest Model, one of the LBVS method, has also been used to predict the activity of these chemical constituents of Ocimum basilicum against the MAO-B. Results: During the docking studies, all the 108 compounds found in Ocimum basilicum were docked within the active site of MAO-B (PDB code: 4A79) out of which, 57 compounds successfully formed the hydrogen bond with tyr 435, a crucial amino acid for the biological activity of the enzyme. Rutin (-182.976 Kcal/mol), Luteolin (-163.171 Kcal/mol), Eriodictyol-7-O-glucoside (- 160.13 Kcal/mol), Rosmarinic acid (-133.484 Kcal/mol) and Isoquercitrin (-131.493 Kcal/mol) are among the top hits with the highest MolDock score along with hydrogen interaction with tyr 435. Using the RF model, ten compounds out of 108 chemical constituent of Ocimum basilicum were predicted to be active, Apigenin (1.0), Eriodictyol (1.0), Orientin (0.876), Kaempferol (0.8536), Luteolin (0.813953) and Rosmarinic-Acid (0.7738095) are predicted to be most active with the highest RF score. Conclusion: The comparison of the two screening methods show that the ten compounds that were predicted to be active by the RF model, are also found in top hits of docking studies with the highest score. The top hits obtained during this study are predicted to be the inhibitor of MAO-B, thus, could be used further for the development of drugs for the treatment of Parkinson’s disease (PD).

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