scholarly journals Based on the Virtual Screening of Multiple Pharmacophores, Docking and Molecular Dynamics Simulation Approaches toward the Discovery of Novel HPPD Inhibitors

2020 ◽  
Vol 21 (15) ◽  
pp. 5546
Author(s):  
Ying Fu ◽  
Tong Ye ◽  
Yong-Xuan Liu ◽  
Jian Wang ◽  
Fei Ye
Keyword(s):  
Coulomb Force ◽  
Docking Study ◽  
Binding Mode ◽  
Homogentisic Acid ◽  
Dynamics Simulation ◽  
Catabolic Pathway ◽  
Molecular Docking Study ◽  
Generalized Born ◽  
Pharmacophore Models ◽  
Important Enzyme

4-Hydroxyphenylpyruvate dioxygenase (HPPD) is an iron-dependent non-heme oxygenase involved in the catabolic pathway of tyrosine, which is an important enzyme in the transformation of 4-hydroxyphenylpyruvic acid to homogentisic acid, and thus being considered as herbicide target. Within this study, a set of multiple structure-based pharmacophore models for HPPD inhibitors were developed. The ZINC and natural product database were virtually screened, and 29 compounds were obtained. The binding mode of HPPD and its inhibitors obtained through molecular docking study showed that the residues of Phe424, Phe381, His308, His226, Gln307 and Glu394 were crucial for activity. Molecular-mechanics-generalized born surface area (MM/GBSA) results showed that the coulomb force, lipophilic and van der Waals (vdW) interactions made major contributions to the binding affinity. These efforts will greatly contribute to design novel and effective HPPD inhibitory herbicides.

Evaluation of the Anticancer and DNA-Binding Characteristics of Dichloro(diimine)zinc(II) Complexes

Chemistry ◽  
2021 ◽  
Vol 3 (4) ◽  
pp. 1178-1188
Author(s):  
Bandar A. Babgi ◽  
Doaa Domyati ◽  
Magda H. Abdellattif ◽  
Mostafa A. Hussien
Keyword(s):  
Dna Binding ◽  
Binding Constants ◽  
Docking Study ◽  
Binding Mode ◽  
Molecular Docking Study ◽  
Binding Characteristics ◽  
Anticancer Properties ◽  
Amino Phenol ◽  
Donor Acceptor ◽  
Diimine Complexes

Several metal diimine complexes have been reported to possess anticancer properties. To evaluate the anticancer properties of tetrahedral zinc(II) diimine complexes, six complexes were synthesized with the general formula M(N^N)Cl2 {where M = Zn, Pt and N^N = 2,2’-biquinoline (1), 2,2’-dipyridylketone (2) and 4-((pyridine-2-ylmethylene)amino)phenol (3)}. In general, the intrinsic DNA-binding constants for the different compounds exhibited values within close proximity; the changes in the viscosity of the CT-DNA upon binding to the compounds suggest intercalation-binding mode. Molecular docking study predicted that complexes containing the highly planar ligand 2,2’-biquinoline are capable to establish π–π interactions with nucleobases of the DNA; the other four complexes engaged in donor–acceptor interactions with DNA nucleobases. The six complexes and two reference drugs (cisplatin and sunitinib) were tested against two cancer cell lines (COLO 205 and RCC-PR) and one normal cell line (LLC-MK2), highlighting the better performance of the zinc(II) complexes compared to their platinum(II) analogues. Moreover, zinc(II) complexes have higher selectivity index values than the reference drugs, with promising anticancer properties.

scholarly journals Exploiting the Reverse Vaccinology Approach to Design Novel Subunit Vaccine against Ebola Virus

2020 ◽  
Author(s):  
Md. Asad Ullah ◽  
Bishajit Sarkar ◽  
Syed Sajidul Islam
Keyword(s):  
Molecular Docking ◽  
Mhc Class Ii ◽  
Large Scale ◽  
Matrix Protein ◽  
Ebola Virus ◽  
Rna Virus ◽  
Docking Study ◽  
Dynamics Simulation ◽  
Molecular Docking Study ◽  
Class I Mhc

AbstractEbola virus is a highly pathogenic RNA virus that causes haemorrhagic fever in human. With very high mortality rate, Ebola virus is considered as one of the dangerous viruses in the world. Although, the Ebola outbreaks claimed many lives in the past, no satisfactory treatment or vaccine have been discovered yet to fight against Ebola. For this reason, in this study, various tools of bioinformatics and immunoinformatics were used to design possible vaccines against Zaire Ebola virus strain Mayinga-76. To construct the vaccine, three potential antigenic proteins of the virus, matrix protein VP40, envelope glycoprotein and nucleoprotein were selected against which the vaccines would be designed. The MHC class-I, MHC class-II and B-cell epitopes were determined and after robust analysis through various tools and molecular docking analysis, three vaccine candidates, designated as EV-1, EV-2 and EV-3, were constructed. Since the highly conserved epitopes were used for vaccine construction, these vaccine constructs are also expected to be effective on other strains of Ebola virus like strain Gabon-94 and Kikwit-95. Next, the molecular docking study on these vaccine constructs were analyzed by molecular docking study and EV-1 emerged as the best vaccine construct. Later, molecular dynamics simulation study revealed the good performances as well as good stability of the vaccine protein. Finally, codon adaptation and in silico cloning were conducted to design a possible plasmid (pET-19b plasmid vector was used) for large scale, industrial production of the EV-1 vaccine.

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

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.

scholarly journals Insight of the Interaction between 2,4-thiazolidinedione and Human Serum Albumin: A Spectroscopic, Thermodynamic and Molecular Docking Study

2019 ◽  
Vol 20 (11) ◽  
pp. 2727 ◽  
Author(s):  
Safikur Rahman ◽  
Md Tabish Rehman ◽  
Gulam Rabbani ◽  
Parvez Khan ◽  
Mohamed F AlAjmi ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Human Serum Albumin ◽  
Serum Albumin ◽  
Human Serum ◽  
Docking Study ◽  
Dynamics Simulation ◽  
Titration Calorimetry ◽  
Peroxisome Proliferator ◽  
Molecular Docking Study ◽  
Fluorescence Studies

Thiazolidinedione derivatives (TZDs) have attracted attention because of their pharmacological effects. For example, certain TZDs have been reported to ameliorate type II diabetes by binding and activating PPARs (peroxisome proliferator-activated receptors). Nonetheless, no information is available on the interaction between the heterocyclic 2, 4-thiazolidinedione (2,4-TZD) moiety and serum albumin, which could affect the pharmacokinetics and pharmacodynamics of TZDs. In this study, we investigated the binding of 2,4-TZD to human serum albumin (HSA). Intrinsic fluorescence spectroscopy revealed a 1:1 binding stoichiometry between 2,4-TZD and HSA with a binding constant (Kb) of 1.69 ± 0.15 × 103 M−1 at 298 K. Isothermal titration calorimetry studies showed that 2,4-TZD/HSA binding was an exothermic and spontaneous reaction. Molecular docking analysis revealed that 2,4-TZD binds to HSA subdomain IB and that the complex formed is stabilized by van der Waal’s interactions and hydrogen bonds. Molecular dynamics simulation confirmed the stability of the HSA-TZD complex. Further, circular dichroism and 3D fluorescence studies showed that the global conformation of HSA was slightly altered by 2,4-TZD binding, enhancing its stability. The results obtained herein further help in understanding the pharmacokinetic properties of thiazolidinedione.

scholarly journals Dual Binding Site and Selective Acetylcholinesterase Inhibitors Derived from Integrated Pharmacophore Models and Sequential Virtual Screening

2014 ◽  
Vol 2014 ◽  
pp. 1-21 ◽  
Author(s):  
Shikhar Gupta ◽  
C. Gopi Mohan
Keyword(s):  
Molecular Docking ◽  
Binding Site ◽  
Enzyme Inhibitors ◽  
Acetylcholinesterase Inhibitors ◽  
Docking Study ◽  
Molecular Docking Study ◽  
Test Set ◽  
Zinc Database ◽  
Pharmacophore Hypotheses ◽  
Pharmacophore Models

In this study, we have employedin silicomethodology combining double pharmacophore based screening, molecular docking, and ADME/T filtering to identify dual binding site acetylcholinesterase inhibitors that can preferentially inhibit acetylcholinesterase and simultaneously inhibit the butyrylcholinesterase also but in the lesser extent than acetylcholinesterase. 3D-pharmacophore models of AChE and BuChE enzyme inhibitors have been developed from xanthostigmine derivatives through HypoGen and validated using test set, Fischer’s randomization technique. The best acetylcholinesterase and butyrylcholinesterase inhibitors pharmacophore hypotheses Hypo1_A and Hypo1_B, with high correlation coefficient of 0.96 and 0.94, respectively, were used as 3D query for screening the Zinc database. The screened hits were then subjected to the ADME/T and molecular docking study to prioritise the compounds. Finally, 18 compounds were identified as potential leads against AChE enzyme, showing good predicted activities and promising ADME/T properties.

scholarly journals Profiling of Potential Antibacterial Compounds of Lactic Acid Bacteria against Extremely Drug Resistant (XDR) Acinetobacter baumannii

Molecules ◽  
2021 ◽  
Vol 26 (6) ◽  
pp. 1727
Author(s):  
Phui-Chyng Yap ◽  
Noorfazlin Ayuhan ◽  
Jia Jie Woon ◽  
Cindy Shuan Ju Teh ◽  
Vannajan Sanghiran Lee ◽  
...  
Keyword(s):  
Antibacterial Activity ◽  
Lactic Acid ◽  
Lactic Acid Bacteria ◽  
Acinetobacter Baumannii ◽  
Docking Study ◽  
Binding Mode ◽  
Gas Chromatography Mass Spectrometry ◽  
Assay Method ◽  
Drug Resistant ◽  
Molecular Docking Study

A total of 20 of isolates of lactic acid bacteria (LAB) were selected and screened for antagonistic activity against clinical strains of 30 clinical isolates of extremely drug-resistant (XDR) Acinetobacter baumannii using the well diffusion assay method. Results showed that 50% of the highly LAB strains possessed inhibitory activity against (up to 66%) of the XDR A. baumannii strains tested. The supernatant of the twenty LAB strains was subjected to gas chromatography mass spectrometry (GCMS) revealed that the common compound found in the active isolates against XDR A. baumannii was 3-Isobutyl-2,3,6,7,8,8a-hexahydropyrrolo[1,2-a]pyrazine-1,4-dione, a known potential diketopiperazine group. The molecular docking study against potential antibacterial targets with selected ligands was performed to predict the binding mode of interactions, which is responsible for antibacterial activity. The docking analysis of the potent compounds supported the potential antibacterial activity exhibiting high inhibition constant and binding affinity in silico.

scholarly journals The Essential Facts of Wuhan Novel Coronavirus Outbreak in China and Epitope-based Vaccine Designing against COVID-19

2020 ◽  
Author(s):  
Bishajit Sarkar ◽  
Md. Asad Ullah ◽  
Fatema Tuz Johora ◽  
Masuma Afrin Taniya ◽  
Yusha Araf
Keyword(s):  
Mass Production ◽  
Docking Study ◽  
Dynamics Simulation ◽  
Definitive Treatment ◽  
Biological Stability ◽  
Molecular Docking Study ◽  
Subunit Vaccines ◽  
Infected People ◽  
Production Strategy ◽  
Novel Coronavirus

AbstractWuhan Novel Coronavirus disease (COVID-19) outbreak has become a global outbreak which has raised the concern of scientific community to design and discover a definitive cure against this deadly virus which has caused deaths of numerous infected people upon infection and spreading. To date, no antiviral therapy or vaccine is available which can effectively combat the infection caused by this virus. This study was conducted to design possible epitope-based subunit vaccines against the SARS-CoV-2 virus using the approaches of reverse vaccinology and immunoinformatics. Upon continual computational experimentation three possible vaccine constructs were designed and one vaccine construct was selected as the best vaccine based on molecular docking study which is supposed to effectively act against SARS-CoV-2. Later, molecular dynamics simulation and in silico codon adaptation experiments were carried out in order to check biological stability and find effective mass production strategy of the selected vaccine. Hopefully, this study will contribute to uphold the present efforts of the researches to secure a definitive treatment against this lethal virus.

scholarly journals MOLECULAR DOCKING STUDY ON 1-(3-(4-BENZYLPIPERAZIN-1-YL)PROPYL)-3,7-DIMETHYL-1H-PURINE-2,6(3H,7H)-DIONE AS AN ACETYLCHOLINESTERASE INHIBITOR

2018 ◽  
Vol 6 ◽  
pp. 898-903
Author(s):  
Maria Hristova ◽  
Mariyana Atanasova ◽  
Iva Valkova ◽  
Lilya Andonova ◽  
Irini Doytchinova ◽  
...  
Keyword(s):  
Active Site ◽  
Acetylcholinesterase Inhibitor ◽  
Docking Study ◽  
Binding Mode ◽  
New Drugs ◽  
Ache Inhibition ◽  
Molecular Docking Study ◽  
Ache Inhibitors ◽  
Good Target ◽  
Catalytic Active Site

Acetylcholinesterase (AChE) is a good target in the design of new drugs for the treatment of Alzheimer’s disease. The currently known drugs -donepezil, galantamine and rivastignime- act as moderate AChE inhibitors. In the present study, we docked a newly synthesized arylpiperazine derivative 1-(3-(4-benzylpiperazin-1-yl)propyl)-3,7-dimethyl-1H-purine-2,6(3H,7H)-dione (LA1) into rhAChE and identified its binding mode. The docking pose of the studied LA1 molecule depends of the protonated state of the nitrogen atom of the piperazine moiety where in the best scored poses, the xanthine moiety of LA1 is bound into the catalytic active site (CAS) of AChE, while the arylpiperazine fragment is placed into the peripheral binding site (PAS). The Ellman’s test confirmed the compound binding. LA1 has good permeability through the GIT and BBB assessed by PAMPA. LA1 is a prospective lead for AChE inhibition.

scholarly journals Synthesis of Diabetic II Inhibitors Based on 2-mercaptobenzimidazole and their Molecular Docking Study

2019 ◽  
Author(s):  
Muhammad Taha ◽  
Fazal Rahim ◽  
Shawkat Hayat ◽  
Manikandan Selvaraj ◽  
Rai Khalid Farooq ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Docking Study ◽  
Binding Mode ◽  
Alpha Amylase ◽  
Variable Degree ◽  
Molecular Docking Study ◽  
Standard Drug ◽  
Ic50 Value ◽  
Ic50 Values ◽  
Inhibitory Potential

In the search of potent α-amylase inhibitors, we have synthesized seventeen derivatives of 2-mercaptobenzimidazole bearing sulfonamide (1-17) and evaluated for their α-amylase inhibitory potential. All compounds display a variable degree of α-amylase activity having IC50 values ranging between 0.90 ± 0.05 to 11.20 ± 0.30 µM when compared with the standard drug acarbose having IC50 value 1.70 ± 0.10 µM. Compound 1, 2, 11, 12 and 14 having IC50 values 1.40 ± 0.10, 1.30 ± 0.05, 0.90 ± 0.05, 1.60 ± 0.05 and 1.60 ± 0.10 µM respectively were found many folds better than the standard drug acarbose. The remaining analogs showed good inhibitory potentials. All the synthesized compounds were characterized by HREI-MS, 1H and 13C-NMR. Structure activity relationship (SAR) has been recognized for all newly synthesized analogs. Through molecular docking study, binding mode of active analogs with α-amylase enzyme was confirmed.

Synthesis, characterization, antitumor potential, BSA and DNA binding properties, and molecular docking study of some novel 3-hydroxy-3-pyrrolin-2-ones

2021 ◽  
Vol 17 ◽  
Author(s):  
Nenad Joksimović ◽  
Jelena Petronijević ◽  
Emilija Milović ◽  
Nenad Janković ◽  
Dejan Baskić ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Docking Study ◽  
Binding Mode ◽  
Biologically Active ◽  
Molecular Docking Study ◽  
Antitumor Potential ◽  
Sw480 Cells ◽  
High Cytotoxicity ◽  
A Minor ◽  
Dna Complex

Background: In order to make progress in discovering the new agents for cancer treatment with improved properties and considering the fact that 3-hydroxy-3-pyrrolin-2-ones belong to a class of biologically active compounds, we tested series of eleven novels 1,5-diaryl-4-(2-thienylcarbonyl)-3-hydroxy-3-pyrrolin-2-ones for their antitumor potential. Methods: All novel compounds were characterized by spectral (IR, NMR, MS) and elemental analysis. All novel 3-hydroxy-3-pyrrolin-2-ones were screened for their cytotoxic activity on two cancer cell lines, SW480 and MDA-MB 231, and non-transformed fibroblasts (MRC-5). Results: Compounds B8, B9, and B10 showed high cytotoxicity on SW480 cells together with good selectivity towards MRC-5 cells. It is important to empathize that the degree of selectivity of B8 and B10 was high (SI = 5.54 and 12.09, respectively). Besides, we explored the mechanisms of cytotoxicity of novel derivatives, B8, B9, and B10. The assay showed that tested derivatives induce an apoptotic type of cell death in SW480 cells, with a minor percent of necrotic cells. Additionally, to better understand the suitability of the compounds for potential use as anticancer medicaments, we studied their interactions with biomacromolecules (DNA or BSA). The results indicated that the tested compounds have a great affinity to displace EB from the EB-DNA complex through intercalation. Also, DNA and BSA molecular docking study was performed to predict the binding mode and the interaction region of the compounds. Conclusion: Achieved results indicate that our compounds have the potential to become candidates for use as medicaments.

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