scholarly journals In silico Assessment of Potential Leads Identified from Bauhinia rufescens Lam. as α-Glucosidase and α-Amylase Inhibitors

2020 ◽  
pp. 27-38
Author(s):  
Wadah Osman ◽  
Esraa M. O. A. Ismail ◽  
Shaza W. Shantier ◽  
Mona S. Mohammed ◽  
Ramzi A. Mothana ◽  
...  
Keyword(s):  
Binding Energy ◽  
In Silico ◽  
Hydrophobic Interactions ◽  
Therapeutic Potential ◽  
Hypoglycemic Agents ◽  
Pharmacokinetic Parameters ◽  
Innovative Drug ◽  
Toxicity Risk ◽  
Autodock 4.0 ◽  
Amylase Inhibitors

Aim: Natural products play a pivotal role in innovative drug discovery by providing structural leads for the development of new therapeutic agents against various diseases. The present study aims to focus on the in silico assessment of the therapeutic potential of antidiabetic phytoconstituents which were identified and isolated from the extracts of Bauhinia rufescens Lam., a medicinal plant traditionally used for various pharmacotherapeutic purposes. Methods: The physicochemical and pharmacokinetic parameters of the isolated thirty eight compounds were predicted using Swiss ADME web tool whereas OSIRIS Property Explorer was used for toxicity risk assessment and drug- likeliness. Twelve compounds were selected for docking on human α-glucosidase and α-amylase enzymes using Autodock 4.0 software. Results and Discussion: Eriodictyol was found to have the highest potential as an inhibitor against α-amylase with binding energy of -9.92 kcal/mol. Rutin was the most potent against α-glucosidase with binding energy of-9.15 kcal/mol. A considerable number of hydrogen bonds and hydrophobic interactions were computed between the compounds and the enzymes thereby making them energetically favorable and suggesting inhibition of these two enzymes as a plausible molecular mechanism for their antidiabetic effect. Conclusion: These two flavonoids could therefore be used as potential leads for structure- based design of new effective hypoglycemic agents.

In-silico screening of 2,3-diphenylquinozaline derivatives as C-met kinase inhibitors

2017 ◽  
Vol 4 (3) ◽  
pp. 41-45
Author(s):  
Nehla Yahcoob ◽  
Baskar Lakshmanan ◽  
Jyothi Achuthanandhan ◽  
Vijayakumar Balakrishnan
Keyword(s):  
Binding Energy ◽  
Tyrosine Kinase ◽  
In Silico ◽  
Kinase Inhibitors ◽  
Therapeutic Potential ◽  
Biological Activities ◽  
Wide Spectrum ◽  
Binding Interaction ◽  
In Silico Screening ◽  
Sar Study

Quinoxaline, an important class of heterocylic compounds drawn greater attention due to their wide spectrum of biological activities. They are considered as an important chemical scaffold for anticancer drug design  due to their potential inhibitory activity against  C-met tyrosine kinase. C-met kinase inhibitors  are a class of small molecules that having therapeutic potential in  the treatment of various types of cancers. The present study aims to focus on the chemistry of quinoxaline derivatives, their potential activities against C-met tyrosine kinase, and in-silico screening of designed compounds. A series of twelve compounds were designed and docked against C-met tyrosine kinase for their binding energy. All compounds were found to be interacting  well with the protein. Compound NQ1 was found to have good binding energy showing an estimated Ki value of  1.1μm.  SAR  study indicated the presence of an electron withdrawing substitution on  benzilidine  phenyl ring of quinoxaline greatly improves its binding interaction with the protein.

scholarly journals In-silico designing of NKK: A better ligand than Aciclovir against Herpes Simplex Virus

2015 ◽  
Vol 3 (01) ◽  
pp. 48-55
Author(s):  
Neelabh . ◽  
K. K. Jeswara ◽  
A. Kumari ◽  
K. Singh
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Binding Energy ◽  
Thymidine Kinase ◽  
In Silico ◽  
Drug Candidate ◽  
Physiochemical Properties ◽  
Autodock 4.0 ◽  
Simplex Virus

Aciclovir is the best dr thymidine kinase made by the HSV. In the current study we have successfully designed a drug candidate “NKK”, which is far more efficient than aciclovir in terms of binding energy and physiochemical properties again used softwares viz. Autodock 4.0, FireDock and Hex dock in order to demonstrate that “NKK” is a better ligand than aciclovir with respect to aforesaid properties.

scholarly journals In silico studies of selected xanthophylls as potential candidates against SARS-CoV-2 targeting main protease (Mpro) and papain-like protease (PLpro)

2021 ◽  
Vol 67 (2) ◽  
pp. 1-8
Author(s):  
Tomasz M. Karpiński ◽  
Marek Kwaśniewski ◽  
Marcin Ożarowski ◽  
Rahat Alam
Keyword(s):  
Binding Energy ◽  
Active Site ◽  
In Silico ◽  
Active Sites ◽  
Data Bank ◽  
Pharmacokinetic Parameters ◽  
Discovery Studio ◽  
Main Protease ◽  
In Silico Studies ◽  
Potential Inhibitors

Summary Introduction: The main protease (Mpro) and the papain-like protease (PLpro) are essential for the replication of SARS-CoV-2. Both proteases can be targets for drugs acting against SARS-CoV-2. Objective: This paper aims to investigate the in silico activity of nine xanthophylls as inhibitors of Mpro and PLpro. Methods: The structures of Mpro (PDB-ID: 6LU7) and PLpro (PDB-ID: 6W9C) were obtained from RCSB Protein Data Bank and developed with BIOVIA Discovery Studio. Active sites of proteins were performed using CASTp. For docking the PyRx was used. Pharmacokinetic parameters of ADMET were evaluated using SwissADME and pkCSM. Results: β-cryptoxanthin exhibited the highest binding energy: –7.4 kcal/mol in the active site of Mpro. In PLpro active site, the highest binding energy had canthaxanthin of –9.4 kcal/mol, astaxanthin –9.3 kcal/mol, flavoxanthin –9.2 kcal/mol and violaxanthin –9.2 kcal/mol. ADMET studies presented lower toxicity of xanthophylls in comparison to ritonavir and ivermectin. Conclusion: Our findings suggest that xanthophylls can be used as potential inhibitors against SARS-CoV-2 main protease and papain-like protease.

Critical Review on the Chemical Aspects of Cannabidiol (CBD) and Harmonization of Computational Bioactivity Data

2020 ◽  
Vol 28 (2) ◽  
pp. 213-237 ◽  
Author(s):  
Andrea Mastinu ◽  
Giovanni Ribaudo ◽  
Alberto Ongaro ◽  
Sara Anna Bonini ◽  
Maurizio Memo ◽  
...  
Keyword(s):  
In Silico ◽  
Cannabis Sativa ◽  
Therapeutic Potential ◽  
The Novel ◽  
In Silico Studies ◽  
Computational Data ◽  
Synthetic Approaches ◽  
Analytical Approaches ◽  
Yield Sensitivity ◽  
Therapeutic Profile

: Cannabidiol (CBD) is a non-psychotropic phytocannabinoid which represents one of the constituents of the “phytocomplex” of Cannabis sativa. This natural compound is attracting growing interest since when CBD-based remedies and commercial products were marketed. This review aims to exhaustively address the extractive and analytical approaches that have been developed for the isolation and quantification of CBD. Recent updates on cutting-edge technologies were critically examined in terms of yield, sensitivity, flexibility and performances in general, and are reviewed alongside original representative results. As an add-on to currently available contributions in the literature, the evolution of the novel, efficient synthetic approaches for the preparation of CBD, a procedure which is appealing for the pharmaceutical industry, is also discussed. Moreover, with the increasing interest on the therapeutic potential of CBD and the limited understanding of the undergoing biochemical pathways, the reader will be updated about recent in silico studies on the molecular interactions of CBD towards several different targets attempting to fill this gap. Computational data retrieved from the literature have been integrated with novel in silico experiments, critically discussed to provide a comprehensive and updated overview on the undebatable potential of CBD and its therapeutic profile.

Lead Molecule Prediction and Characterization for Designing MERS-CoV 3C-like Protease Inhibitors: An In silico Approach

2018 ◽  
Vol 15 (1) ◽  
pp. 82-88 ◽  
Author(s):  
Md. Mostafijur Rahman ◽  
Md. Bayejid Hosen ◽  
M. Zakir Hossain Howlader ◽  
Yearul Kabir
Keyword(s):  
Binding Energy ◽  
Middle East ◽  
Virtual Screening ◽  
In Silico ◽  
Screening Method ◽  
Middle East Respiratory Syndrome ◽  
Cytochrome P450 Enzymes ◽  
Drug Molecules ◽  
Essential Enzyme ◽  
Reduced Toxicity

Background: 3C-like protease also called the main protease is an essential enzyme for the completion of the life cycle of Middle East Respiratory Syndrome Coronavirus. In our study we predicted compounds which are capable of inhibiting 3C-like protease, and thus inhibit the lifecycle of Middle East Respiratory Syndrome Coronavirus using in silico methods. </P><P> Methods: Lead like compounds and drug molecules which are capable of inhibiting 3C-like protease was identified by structure-based virtual screening and ligand-based virtual screening method. Further, the compounds were validated through absorption, distribution, metabolism and excretion filtering. Results: Based on binding energy, ADME properties, and toxicology analysis, we finally selected 3 compounds from structure-based virtual screening (ZINC ID: 75121653, 41131653, and 67266079) having binding energy -7.12, -7.1 and -7.08 Kcal/mol, respectively and 5 compounds from ligandbased virtual screening (ZINC ID: 05576502, 47654332, 04829153, 86434515 and 25626324) having binding energy -49.8, -54.9, -65.6, -61.1 and -66.7 Kcal/mol respectively. All these compounds have good ADME profile and reduced toxicity. Among eight compounds, one is soluble in water and remaining 7 compounds are highly soluble in water. All compounds have bioavailability 0.55 on the scale of 0 to 1. Among the 5 compounds from structure-based virtual screening, 2 compounds showed leadlikeness. All the compounds showed no inhibition of cytochrome P450 enzymes, no blood-brain barrier permeability and no toxic structure in medicinal chemistry profile. All the compounds are not a substrate of P-glycoprotein. Our predicted compounds may be capable of inhibiting 3C-like protease but need some further validation in wet lab.

Antihyperglycemic, Antioxidant and Hepatoprotective Properties of Smilax wightii A.DC. : an Endemic Plant of Western Ghats

2020 ◽  
pp. 584-589
Author(s):  
Athira V. Anand ◽  
T. S. Swapna
Keyword(s):  
Diabetes Mellitus ◽  
Therapeutic Potential ◽  
Radical Scavenging Activity ◽  
Radical Scavenging ◽  
Hypoglycemic Agents ◽  
Endemic Plant ◽  
Plant Parts ◽  
Total Antioxidant ◽  
A Cell ◽  
Viability Percentage

Phytotherapy is an inevitable companion of human civilization. Smilax wightii is an ethnomedicinal plant in Smilacaceae, with unexplored scientifically therapeutic potential. The antihyperglycemic, antioxidant and hepatoprotective capabilities of the methanolic extract of leaf, stem, rhizome and root of S. wightii were inspected in the present study. Hyperglycemia is a manifestation of the prevalent metabolic disorder, Type 2 Diabetes mellitus. Inhibitors of α –glucosidase and α – amylase could be efficiently employed in diabetes mellitus therapy as hypoglycemic agents. In the α –glucosidase and α – amylase inhibitory assays, root and rhizome extracts recorded better antihyperglycemic activity. DPPH radical scavenging activity and total antioxidant capacity were the parameters employed to determine the antioxidant activity. Hepatoprotectivity determines the capability of samples to safeguard the hepatocytes from damage. Novel hepatoprotective agents are in demand since the incidence of liver impairment is on a high among global population. The rhizome extract showed comparatively superior hepatoprotectivity followed by the leaf, stem and root extracts. Rhizome, at 100μg/ml guaranteed a cell viability percentage of 77.43 in the Chang liver cell line treated with Carbon tetrachloride. So the root and rhizome of S. wightii are the therapeutically significant plant parts with hypoglycemic, free radical scavenging and hepatoprotective potentialities.

In silico discovery and therapeutic potential of IDO1 and TDO2 inhibitors

2017 ◽  
Vol 9 (12) ◽  
pp. 1309-1311 ◽  
Author(s):  
Finith E Jernigan ◽  
Lijun Sun
Keyword(s):  
In Silico ◽  
Therapeutic Potential

scholarly journals Screening of Chloroquine, Hydroxychloroquine and Its Derivatives for Their Binding Affinity to Multiple SARS-CoV-2 Protein Drug Targets

2020 ◽  
Author(s):  
Mallikarjuna Nimgampalle ◽  
Vasudharani Devanthan ◽  
Ambrish Saxena
Keyword(s):  
Binding Affinity ◽  
In Silico ◽  
Drug Targets ◽  
Therapeutic Potential ◽  
Viral Proteins ◽  
Protein Drug ◽  
Potential Treatment ◽  
Health Authorities ◽  
Derivatives Of

Recently Chloroquine and its derivative Hydroxychloroquine have garnered enormous interest amongst the clinicians and health authorities’ world over as a potential treatment to contain COVID-19 pandemic. The present research aims at investigating the therapeutic potential of Chloroquine and its potent derivative Hydroxychloroquine against SARS-CoV-2 viral proteins. At the same time we have screened some chemically synthesized derivatives of Chloroquine and compared their binding efficacy with chemically synthesized Chloroquine derivatives through <i>in silico</i>approaches. For the purpose of the study, we have selected some essential viral proteins and enzymes implicated in SARS-CoV-2 replication and multiplication as putative drug targets.<br>

scholarly journals Anti-Methanogenic Effect of Phytochemicals on Methyl-Coenzyme M Reductase—Potential: In Silico and Molecular Docking Studies for Environmental Protection

Micromachines ◽  
2021 ◽  
Vol 12 (11) ◽  
pp. 1425
Author(s):  
Yuvaraj Dinakarkumar ◽  
Jothi Ramalingam Rajabathar ◽  
Selvaraj Arokiyaraj ◽  
Iyyappan Jeyaraj ◽  
Sai Ramesh Anjaneyulu ◽  
...  
Keyword(s):  
Molecular Docking ◽  
In Silico ◽  
Rosmarinic Acid ◽  
Docking Studies ◽  
Thymus Vulgaris ◽  
Piper Betle ◽  
Coenzyme M ◽  
Dynamics Simulations ◽  
Autodock 4.0 ◽  
Methyl Coenzyme M Reductase

Methane is a greenhouse gas which poses a great threat to life on earth as its emissions directly contribute to global warming and methane has a 28-fold higher warming potential over that of carbon dioxide. Ruminants have been identified as a major source of methane emission as a result of methanogenesis by their respective gut microbiomes. Various plants produce highly bioactive compounds which can be investigated to find a potential inhibitor of methyl-coenzyme M reductase (the target protein for methanogenesis). To speed up the process and to limit the use of laboratory resources, the present study uses an in-silico molecular docking approach to explore the anti-methanogenic properties of phytochemicals from Cymbopogon citratus, Origanum vulgare, Lavandula officinalis, Cinnamomum zeylanicum, Piper betle, Cuminum cyminum, Ocimum gratissimum, Salvia sclarea, Allium sativum, Rosmarinus officinalis and Thymus vulgaris. A total of 168 compounds from 11 plants were virtually screened. Finally, 25 scrutinized compounds were evaluated against methyl-coenzyme M reductase (MCR) protein using the AutoDock 4.0 program. In conclusion, the study identified 21 out of 25 compounds against inhibition of the MCR protein. Particularly, five compounds: rosmarinic acid (−10.71 kcal/mol), biotin (−9.38 kcal/mol), α-cadinol (−8.16 kcal/mol), (3R,3aS,6R,6aR)-3-(2H-1,3-benzodioxol-4-yl)-6-(2H-1,3-benzodioxol-5-yl)-hexahydrofuro[3,4-c]furan-1-one (−12.21 kcal/mol), and 2,4,7,9-tetramethyl-5decyn4,7diol (−9.02 kcal/mol) showed higher binding energy towards the MCR protein. In turn, these compounds have potential utility as rumen methanogenic inhibitors in the proposed methane inhibitor program. Ultimately, molecular dynamics simulations of rosmarinic acid and (3R,3aS,6R,6aR) -3-(2H-1,3-benzodioxol-4-yl)-6-(2H-1,3-benzodioxol-5-yl)-hexahydrofuro[3,4-c]furan-1-one yielded the best possible interaction and stability with the active site of 5A8K protein for 20 ns.

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