Novel Guanosine Derivatives as Anti-HCV NS5b Polymerase: A QSAR and Molecular Docking Study

Background: IDX-184 is a guanosine derivative having a potent inhibitory performance against HCV NS5b polymerase. Objective: To test three different groups of 2'C - modified analogues of guanosine nucleotide against HCV polymerase. Method: Using combined Quantitative Structure-Activity Relationships (QSAR) and molecular docking, the suggested compounds are studied. Results: Examining the docked structures of the compounds with experimentally solved NS5b structure (PDB ID: 2XI3) revealed that most of the compounds have the same mode of interaction as that of guanosine nucleotide and hence, NS5b inhibition is possible. Conclusion: It is revealed that sixteen modifications have a better binding affinity to NS5b compared to guanosine. In addition, seven more compounds are better in NS5b binding compared to the approved drug, sofosbuvir, and the compound under clinical trials, IDX-184. Hence, these compounds could be potent HCV NS5b inhibitors. Summary Points: Novel guanosine modifications were introduced in silico and optimized using QM. QSAR and docking calculations are performed to test the binding affinity of the compounds to HCV NS5b active site. Comparison between the binding affinities and the mode of interactions of the compounds and both GTP and IDX-184 is performed. Structural mining to quantify the mode of binding of the compounds to NS5b active site pocket.

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Molecular Docking Evaluation of Syzygium aromaticum Isolated Compounds Against Exo-β-(1,3)-glucanases of Candida albicans

Journal of Pharmaceutical Research International ◽

10.9734/jpri/2020/v32i4631100 ◽

2021 ◽

pp. 34-44

Author(s):

Mohammed H. F. Shalayel ◽

Ghassab M. Al-Mazaideh ◽

Farhan Khashim Al Swailmi ◽

Saleem Aladaileh ◽

Saada Nour ◽

...

Keyword(s):

Candida Albicans ◽

Molecular Docking ◽

Active Site ◽

Inhibitory Activity ◽

Docking Study ◽

Syzygium Aromaticum ◽

Binding Affinities ◽

Molecular Docking Study ◽

Pubchem Database

Seventeen compounds from Syzygium aromaticum are selected for exo-β-(1,3)-glucanases inhibitory activity by using molecular docking study. The compounds are uploaded from the PubChem database and molecular docking with AutoDock 1.5.6 tools is carried out. The molecular docking scores indicate that stigmasterol and campesterol are of the highest potentials, and approximately have similar binding affinities with Candida albicans' active site (3N9K, 3O6A). The hydroxyl moiety has played an important role in the antifungal potentiality of all studied compounds.

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Plectrabarbene, a New Abietane Diterpene from Plectranthus barbatus Aerial Parts

Molecules ◽

10.3390/molecules25102365 ◽

2020 ◽

Vol 25 (10) ◽

pp. 2365

Author(s):

Nawal M. Al Musayeib ◽

Musarat Amina ◽

Gadah Abdulaziz Al-Hamoud ◽

Gamal A. Mohamed ◽

Sabrin R.M. Ibrahim ◽

...

Keyword(s):

Molecular Docking ◽

Binding Affinity ◽

Active Site ◽

Docking Study ◽

Inhibition Mechanism ◽

Ache Inhibition ◽

Molecular Docking Study ◽

Spectral Techniques ◽

Aerial Parts ◽

Insight Into

A new abietane diterpene namely plectrabarbene (2), together with two known compounds: sugiol (1) and 11,14-dihydroxy-8,11,13-abietatrien-7-one (3) have been isolated from the aerial parts of Plectranthus barbatus Andr. (Labiatae). The structures of these compounds were determined by various spectral techniques (e.g., UV, IR, NMR, and FAB) and by comparison with the literature data. A molecular docking study of the isolated diterpenes (1–3) was performed with AChE to gain an insight into their AChE inhibition mechanism. The results of docking experiments revealed that the all tested compounds showed binding affinity at the active site of AchE in comparison to donepezil.

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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

Medicinal Chemistry ◽

10.2174/1573406415666190724142951 ◽

2020 ◽

Vol 16 (7) ◽

pp. 892-902 ◽

Cited By ~ 3

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.

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Novel Group of AChE Reactivators—Synthesis, In Vitro Reactivation and Molecular Docking Study

Molecules ◽

10.3390/molecules23092291 ◽

2018 ◽

Vol 23 (9) ◽

pp. 2291 ◽

Cited By ~ 5

Author(s):

David Malinak ◽

Eugenie Nepovimova ◽

Daniel Jun ◽

Kamil Musilek ◽

Kamil Kuca

Keyword(s):

Molecular Docking ◽

Molecular Modelling ◽

Active Site ◽

Molecular Design ◽

Docking Study ◽

The Novel ◽

Molecular Docking Study ◽

Causal Treatment ◽

Modelling Study

The acetylcholinesterase (AChE) reactivators (e.g., obidoxime, asoxime) became an essential part of organophosphorus (OP) poisoning treatment, together with atropine and diazepam. They are referred to as a causal treatment of OP poisoning, because they are able to split the OP moiety from AChE active site and thus renew its function. In this approach, fifteen novel AChE reactivators were determined. Their molecular design originated from former K-oxime compounds K048 and K074 with remaining oxime part of the molecule and modified part with heteroarenium moiety. The novel compounds were prepared, evaluated in vitro on human AChE (HssAChE) inhibited by tabun, paraoxon, methylparaoxon or DFP and compared to commercial HssAChE reactivators (pralidoxime, methoxime, trimedoxime, obidoxime, asoxime) or previously prepared compounds (K048, K074, K075, K203). Some of presented oxime reactivators showed promising ability to reactivate HssAChE comparable or higher than the used standards. The molecular modelling study was performed with one compound that presented the ability to reactivate GA-inhibited HssAChE. The SAR features concerning the heteroarenium part of the reactivator’s molecule are described.

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Identification of Compounds from Nigella Sativa as New Potential Inhibitors of 2019 Novel Coronasvirus (Covid-19): Molecular Docking Study.

10.26434/chemrxiv.12055716.v1 ◽

2020 ◽

Cited By ~ 9

Author(s):

Salim Bouchentouf ◽

Noureddine Missoum

Keyword(s):

Molecular Docking ◽

Active Site ◽

Nigella Sativa ◽

Specific Treatment ◽

Docking Study ◽

Clinical Test ◽

Molecular Docking Study ◽

Great Opportunity ◽

Drug Candidates ◽

Energy Score

The spread of the global COVID-19 pandemic, the lack of specific treatment and the urgent situation requires use of all resources to remedy this scourge. In the present study, using molecular docking, we identify new probable inhibitors of COVID-19 by molecules from Nigella sativa L, which is highly reputed healing herb in North African societies and both Islamic and Christian traditions. The discovery of the Mpro protease structure in COVID-19 provides a great opportunity to identify potential drug candidates for treatment. Focusing on the main proteases in CoVs (3CLpro/Mpro) (PDB ID 6LU7 and 2GTB); docking of compounds from Nigella Sativa and drugs under clinical test was performed using Molecular Operating Environment software (MOE). Nigelledine docked into 6LU7 active site gives energy complex about -6.29734373 Kcal/mol which is close to the energy score given by chloroquine (-6.2930522 Kcal/mol) and better than energy score given by hydroxychloroquine (-5.57386112 Kcal/mol) and favipiravir (-4.23310471 kcal/mol). Docking into 2GTB active site showed that α- Hederin gives energy score about-6.50204802 kcal/mol whcih is better energy score given by chloroquine (-6.20844936 kcal/mol), hydroxychloroquine (-5.51465893 kcal/mol)) and favipiravir (-4.12183571kcal/mol). Nigellidine and α- Hederin appeared to have the best potential to act as COVID-19 treatment. Further, researches are necessary to testify medicinal use of identified and to encourage preventive use of Nigella Sativa against coronavirus infection.

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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 <div> </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. </div>

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Isoniazid-Isatin Hydrazone Derivatives: Synthesis, Antitubercular Activity and Molecular Docking Studies

Trends in Sciences ◽

10.48048/tis.2021.39 ◽

2021 ◽

Vol 18 (21) ◽

pp. 39

Author(s):

Mardi Santoso ◽

Muhammad Riza Ghulam Fahmi ◽

Yehezkiel Steven Kurniawan ◽

Taslim Ersam ◽

Sri Fatmawati ◽

...

Keyword(s):

Hydrogen Bonding ◽

Mycobacterium Tuberculosis ◽

Molecular Docking ◽

Active Site ◽

Antitubercular Activity ◽

Docking Study ◽

Positive Control ◽

Tuberculosis H37rv ◽

Molecular Docking Study

This study examined the synthesis of isoniazid-isatin hydrazone derivatives 5-7, followed by an investigation on the in vitro antitubercular activity against Mycobacterium tuberculosis H37Rv, and molecular docking. A yield of 81 - 92 % of these compounds was achieved, with structural characterization by spectroscopic methods (FTIR, NMR, HRMS). The in vitro antitubercular activity was evaluated against M. tuberculosis H37Rv, and the highest effect was observed in compound 7, with a minimum inhibitory concentration (MIC) of 0.017 mM, lower than rifampicin (MIC 0.048 mM), which served as the positive control. In addition, the molecular docking of 5-7 was performed to visualize the interaction of isoniazid-isatin hydrazone derivatives with the active site of InhA receptor, which was in agreement with the experimental data. The hydrogen bonding with Ser94 and pi-pi interaction with Phe41 and/or Phe97 on the InhA active site was pivotal for the antitubercular activity. HIGHLIGHTS Tuberculosis caused by Mycobacterium tuberculosis is one of the top ten leading causes of death globally The first and second lines of antituberculosis drugs are the prevalent treatment for this disease, but they show several drawbacks and are exacerbated by the occurrence of drug resistance The isoniazid-isatin hydrazone derivatives were designed through molecular hybridization and synthesized effectively and exhibited moderate to high activity against tuberculosis H37Rv Molecular docking study demonstrated that the hydrogen bonding with Ser94 and the pi-pi interaction with Phe41 and/or Phe97 are important for antitubercular activity GRAPHICAL ABSTRACT

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Molecular Docking Study and ADMET Profile: Manipulation of Angiotensin II Pathophysiology in COVID-19 by Potentilla Reptans Root Compounds

10.21203/rs.3.rs-1120002/v1 ◽

2021 ◽

Author(s):

Ayesheh Enayati ◽

Hassan Mirzaei ◽

Vahid Khori ◽

Ali Jabbari ◽

Aref Salehi ◽

...

Keyword(s):

Molecular Docking ◽

Angiotensin Ii ◽

Active Site ◽

Inflammatory Responses ◽

Cardiac Injury ◽

Ethyl Acetate Fraction ◽

Docking Study ◽

Angiotensin Ii Receptor ◽

Molecular Docking Study ◽

Potentilla Reptans

Abstract In the novel SARS-CoV-2 (COVID-19) as a global emergency event, the main reason of the cardiac injury from COVID-19 is angiotensin-converting enzyme 2 (ACE2) targeting in SARS-CoV-2 infection. The inhibition of ACE2 induces an increase in the angiotensin II (Ang II) and the angiotensin II receptor type 1 (AT1R) leading to impaired cardiac function or cardiac inflammatory responses. The ethyl acetate fraction of Potentilla reptans L. root can rescue heart dysfunction, oxidative stress, cardiac arrhythmias and apoptosis. Therefore, isolated components of P. reptans evaluated to identify natural anti-SARS-CoV-2 agents via molecular docking. In silico molecular docking study were carried out using the Auto Dock software on the isolated compounds of Potentilla reptans root. The protein targets of selective ACE and others obtained from Protein Data Bank (PDB). The best binding pose between amino acid residues involved in active site of the targets and compounds was discovered via molecular docking. Furthermore, ADMET properties of the compounds were evaluated. The triterpenoids of P. reptans showed more ACE inhibitory potential than catechin in both domains. They were selective on the nACE domain, especially compound 5. Also, the compound 5 & 6 had the highest binding affinity toward active site of nACE, cACE, AT1R, ACE2, and TNF-α receptors. Meanwhile, compound 3 showed more activity to inhibit TXA2. Drug likeness and ADMET analysis showed that the compounds passed the criteria of drug likeness and Lipinski rules. The current study depicted that P. reptans root showed cardioprotective effect in COVID-19 infection and manipulation of angiotensin II-induced side effects.

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In silico Molecular Docking Study to Search New SGLT2 Inhibitor based on Dioxabicyclo[3.2.1] Octane Scaffold

Current Computer - Aided Drug Design ◽

10.2174/1573409914666181019165821 ◽

2020 ◽

Vol 16 (2) ◽

pp. 145-154 ◽

Cited By ~ 2

Author(s):

Shubham Kumar ◽

Gopal L. Khatik ◽

Amit Mittal

Keyword(s):

Molecular Docking ◽

Binding Affinity ◽

In Silico ◽

Promising Result ◽

Sglt2 Inhibitor ◽

Docking Study ◽

Sglt2 Inhibitors ◽

Molecular Structures ◽

Molecular Docking Study ◽

Us Fda

Background: Diabetes is a leading cause of high mortality rate in the world. Recently, SGLT2 inhibitors showed the promising result to treat diabetes and therefore several molecules are approved by the US FDA. Objective: SGLT2 inhibitors were designed based on dioxabicyclo[3.2.1] octane with the aim to search new lead molecule. Methods: The molecular structures were drawn in ChemBiodraw ultra and molecular docking study was performed by AutoDock Vina 1.5.6 software. The LogP and toxicity were predicted online using AlogP and Lazar in-silico respectively. Results: Among all the designed molecules, SK306 showed the maximum binding affinity against the 3dh4 SGLT2 protein of Vibrio parahaemolyticus. LogP values were also calculated in order to determine the lipophilic property of the best binding molecules which show LogP 2.82-3.79 in the range for good absorption and elimination, also predicted to be non-toxic. Conclusion: SGLT2 inhibitors were designed based on the dioxabicyclo [3.2.1] octane resulting in a new lead molecule with high binding affinity; also these molecules were predicted to be noncarcinogenic with low LogP.

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IDENTIFICATION OF NOVEL 5-STYRYL-1,2,4-OXADIAZOLE/TRIAZOLE DERIVATIVES AS THE POTENTIAL ANTI-ANDROGENS THROUGH MOLECULAR DOCKING STUDY

International Journal of Pharmacy and Pharmaceutical Sciences ◽

10.22159/ijpps.2016v8i10.13844 ◽

2016 ◽

Vol 8 (10) ◽

pp. 72 ◽

Cited By ~ 3

Author(s):

Paranjeet Kaur ◽

Gopal L. Khatik

Keyword(s):

Molecular Docking ◽

Androgen Receptor ◽

Binding Affinity ◽

Docking Study ◽

Molecular Structures ◽

The Novel ◽

Autodock Vina ◽

Molecular Docking Study ◽

Triazole Derivatives ◽

Better Than

Objective: To identify the novel and simple bioactive antiandrogens, that can overcome to side effects as well as drug resistance.Methods: The AutoDock Vina (ADT) 1.5.6 software is used for molecular docking purposes. The molecular structures were drawn in ChemBiodraw ultra and by the help of ChemBiodraw 3D, all structures were energy minimized by MM2 method and converted to pdb extension file which is readable at the ADT interface.Results: Total ten compounds from both series were shown better binding affinity than R-bicalutamide including oxadiazole and triazole series. Among these pk42 and pk46 were studied in-depth which showed best binding affinity to the androgen receptor. The cis-isomers were found better than their trans-isomer.Conclusion: Novel 5-styryl-1,2,4-oxadiazole/triazole derivatives were studied through molecular modeling using Autodock Vina. The potent compounds which showed better binding affinity than R-bicalutamide like pk24 and 46 were further analyzed for their interactions. The conformational effect also found significant in binding to the androgen receptor.

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